A Rare Cause of Cardiac Hypertrophy: Danon Disease

A Rare Cause of Cardiac Hypertrophy: Danon Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Rare Cause of Cardiac Hypertrophy: Danon Disease Ramazan Anıl Eşki, Cem Korucu, Zafer Yalım This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8310373/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Cardiac hypertrophy is a common clinical finding and may appear as a cardiac manifestation of numerous diseases. In addition to frequently encountered causes such as hypertension and valvular heart disease, clinicians must also consider cardiac amyloidosis, hypertrophic cardiomyopathies, and various rare genetic conditions. Danon disease is a rare X-linked dominant multisystem disorder characterized by cardiomyopathy, skeletal myopathy, and intellectual disability. It results from defects in the lysosome-associated membrane protein-2 (LAMP2) gene, and numerous pathogenic mutations have been described. Here, we present the case of a 64-year-old woman who was evaluated for suspected cardiac amyloidosis due to marked left ventricular hypertrophy and was subsequently diagnosed with Danon disease. The coexistence of Danon disease and cardiac amyloidosis is exceedingly uncommon and highlights the importance of considering rare etiologies in patients presenting with hypertrophic phenotypes. Danon disease LAMP2 gene cardiac hypertrophy cardiac amyloidosis Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Danon disease was first described in 1981 in male members of a family presenting with proximal muscle weakness and concomitant myocardial hypertrophy (1). Limited studies in patients with hypertrophic cardiomyopathy (HCM) have reported Danon disease prevalence rates of 4–6% in pediatric patients, 0.7–4% in adults with HCM, 6–8% in adults with symmetric HCM, and 17–30% in patients with HCM accompanied by pre-excitation (2). The disease is caused by confirmed mutations in the LAMP2 gene (Xq24–q25), leading to loss of LAMP-2 protein expression. More than 60 pathogenic variants have been identified to date (3). LAMP-2 deficiency results in impaired lysosomal degradation and accumulation of autophagic material within cells. This leads to mitochondrial oxidative stress, increased apoptosis, altered metabolic pathways, and reduced calcium handling, ultimately causing contractile dysfunction (4). Although Danon disease is an important cause of cardiac hypertrophy, numerous other etiologies must also be considered. Besides common causes such as hypertension, valvular disease, and age-related changes, cardiac amyloidosis—particularly in elderly patients—should remain an important differential diagnosis. In this case report, we present a rare coexistence of Danon disease and cardiac amyloidosis in a woman with left ventricular hypertrophy and heterogeneous clinical features. CASE PRESENTATION A 64-year-old woman presented with exertional dyspnea, palpitations, hand paresthesia, and fatigue. She denied chest pain, syncope, learning difficulties, cognitive impairment, or visual disturbances. Her symptoms had progressively worsened in recent months. Past medical history included hypertension, diabetes mellitus, asthma, chronic venous insufficiency, deep vein thrombosis, cervical disc herniation, bilateral carpal tunnel syndrome, and vertigo. There was no family history of sudden cardiac death. Neuromuscular examination revealed no significant muscle weakness. Her medications included: acetylsalicylic acid 100 mg daily, valsartan 160 mg + hydrochlorothiazide 12.5 mg daily, trimetazidine 35 mg twice daily, colchicine 0.5 mg twice daily, calcium dobesilate 500 mg twice daily, alpha-lipoic acid 600 mg daily, desloratadine/montelukast daily, inhaled salmeterol/fluticasone, metformin 1000 mg twice daily, and famotidine 40 mg daily. Electrocardiography (Fig. 1 ) revealed sinus rhythm with a heart rate of 68 bpm, PR interval of 230 ms, and first-degree atrioventricular block. Blood pressure was 125/75 mmHg. Peripheral pulses were palpable, and findings of venous insufficiency were present. Echocardiography (Fig. 2 ) showed an ejection fraction of 60%, interventricular septal thickness of 15 mm, posterior wall thickness of 13 mm, LVEDD 45 mm, LVESD 23 mm, and mild mitral and tricuspid regurgitation. Pulmonary artery systolic pressure was 30 mmHg. Diastolic function parameters included E/A: 0.8, E/E′: 10.5, lateral annular S′: 6 cm/s, E′: 6.7 cm/s, and A′: 11.2 cm/s. LVOT gradient was within normal limits. Laboratory evaluation revealed elevated pro-BNP (767.4 ng/L), while renal and hepatic markers were within normal range except for mild LDH elevation. Given the presence of left ventricular hypertrophy, diastolic dysfunction, and bilateral carpal tunnel syndrome, cardiac amyloidosis was strongly suspected. Bone scintigraphy (Tc-PYP) demonstrated Grade 2 myocardial uptake. Serum/urine electrophoresis and serum free light chain analysis excluded monoclonal gammopathy. Genetic testing identified a heterozygous LAMP2 (NM_002294) c.755T > C (p.I252T) variant, confirming Danon disease. Pedigree analysis identified the same mutation in her children and siblings (Fig. 3 ). Holter monitoring revealed no significant arrhythmias. The patient was referred to neurology, ophthalmology, and physical medicine departments for multidisciplinary follow-up alongside cardiology. DISCUSSION Danon disease was originally categorized in 1981 as an X-linked glycogen storage disorder presenting with cardiomyopathy, mental retardation, and myopathy, initially distinguished from Pompe disease due to normal acid maltase levels (1). In 2000, Nishino et al. identified LAMP2 mutations as the underlying cause of the disease through impaired lysosomal function (5). It manifests as severe multisystem involvement, typically with hypertrophic cardiomyopathy, skeletal myopathy, and cognitive deficits in males, whereas females often show milder phenotypes (6). More than one-third of cases arise from de novo mutations (7). The global HCM prevalence is approximately 0.2%, and Danon disease accounts for ~ 1% of index HCM cases, 3% of non-sarcomeric HCM cases, and 4% of genetically analyzed cohorts (8). Thus, Danon disease should always be considered—particularly in atypical or severe hypertrophic phenotypes. LAMP2 deficiency results in impaired autophagosome-lysosome fusion, accumulation of dysfunctional mitochondria, metabolic impairment, and oxidative stress (9–11). Diagnosis relies on genetic confirmation, although biopsy may demonstrate cytoplasmic vacuoles containing autophagic material and glycogen. Our case demonstrates the heterogeneous clinical spectrum within the same family; although our patient exhibited significant hypertrophy and symptomatic burden, her son showed only mild hypertrophy. Female carriers often display variable phenotypes due to differences in X-chromosome inactivation (12). In our patient, diagnosis was made at a relatively advanced age, which is less typical but reported in the literature. Cardiac involvement occurs in 96% of patients and is the major determinant of prognosis. While males typically exhibit hypertrophic cardiomyopathy, females may present with either hypertrophic (33%) or dilated (28%) patterns (13). Pre-excitation (WPW pattern) is common, found in up to 69% of cases (13,15), while arrhythmias—including atrial fibrillation, supraventricular tachycardias, and ventricular arrhythmias—occur in approximately 60% of individuals. Conduction disease (high-degree AV block, sinus node dysfunction) is also frequent (7). In contrast, our patient exhibited only a first-degree AV block. Skeletal myopathy manifests as progressive proximal weakness but is often mild in females. Cognitive impairment is also more common in males. Our patient and her relatives did not show notable cognitive abnormalities. Management requires a multidisciplinary approach. Regular cardiology follow-up with ECG, echocardiography, natriuretic peptides, and Holter monitoring is essential. Cardiac MRI may help identify fibrosis and arrhythmic risk. No disease-specific medical therapy exists; treatment is aimed at managing heart failure and arrhythmias. β-blockers, diuretics, and antiarrhythmics may be used as indicated. ICD implantation should be considered in patients with significant hypertrophy, fibrosis, symptomatic arrhythmias, or a family history of sudden cardiac death. Advanced therapies—including transplantation and electrophysiological interventions—may be required. In our case, the additional presence of Grade 2 myocardial uptake suggesting transthyretin amyloidosis represents a rare and clinically challenging scenario. There is limited evidence on the coexistence of Danon disease and amyloidosis, and decisions regarding amyloidosis-specific therapy remain individualized. CONCLUSION Danon disease should be considered in the differential diagnosis of unexplained left ventricular hypertrophy, even in older female patients and in the presence of features suggestive of cardiac amyloidosis. Genetic evaluation plays a pivotal role in diagnosis, and family screening is essential. The coexistence of Danon disease and cardiac amyloidosis, as in our patient, underscores the importance of comprehensive clinical evaluation and multidisciplinary management. Abbreviations AV atrioventricular ECG electrocardiography EF ejection fraction HCM hypertrophic cardiomyopathy IVSd interventricular septal thickness in diastole LAMP2 lysosome-associated membrane protein-2 LV left ventricle LVEDD left ventricular end-diastolic diameter LVESD left ventricular end-systolic diameter PABs pulmonary artery systolic pressure PR PR interval Tc-PYP technetium-99m pyrophosphate. Declarations Ethics approval and consent to participate Not applicable. Ethics committee approval was not required for this case report according to the policies of our institution. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Competing interests The authors declare that they have no competing interests. Funding No funding was received for this study. Author Contribution Ramazan Anıl Eşki evaluated and examined the patient during the initial clinical presentation and collected the clinical data. Cem Korucu performed and interpreted the echocardiographic and imaging assessments. Zafer Yalım supervised the diagnostic process, contributed to the clinical interpretation of findings, and guided the planning and development of the manuscript. All authors contributed to the drafting and critical revision of the manuscript, approved the final version, and agree to be accountable for all aspects of the work. Acknowledgements Not applicable. Data Availability Not applicable. All relevant data are included within the manuscript. References Danon MJ, Oh SJ, DiMauro S, Manaligod JR, Eastwood A, Naidu S, et al. Lysosomal glycogen storage disease with normal acid maltase. Neurology [Internet]. 1981 [cited 2025 Jan 23];31(1):51–7. Available from: https://pubmed.ncbi.nlm.nih.gov/6450334/ Wang Y, Jia M, Guo Y, Zhang T, Ning B. Case Report: Danon Disease: Six Family Members and Literature Review. Front Cardiovasc Med [Internet]. 2022 May 20 [cited 2025 Jan 23];9:842282. Available from: www.frontiersin.org Cheng Z, Fang Q. Danon disease: focusing on heart. J Hum Genet [Internet]. 2012 Jul [cited 2025 Jan 25];57(7):407–10. Available from: https://pubmed.ncbi.nlm.nih.gov/22695892/ Chi C, Leonard A, Knight WE, Beussman KM, Zhao Y, Cao Y, et al. LAMP-2B regulates human cardiomyocyte function by mediating autophagosome–lysosome fusion. Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):556–65. Nishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T, et al. Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature [Internet]. 2000 Aug 24 [cited 2025 Jan 25];406(6798):906–10. Available from: https://pubmed.ncbi.nlm.nih.gov/10972294/ Cenacchi G, Papa V, Pegoraro V, Marozzo R, Fanin M, Angelini C. Review: Danon disease: Review of natural history and recent advances. Neuropathol Appl Neurobiol [Internet]. 2020 Jun 1 [cited 2025 Jan 25];46(4):303–22. Available from: https://pubmed.ncbi.nlm.nih.gov/31698507/ Hong KN, Eshraghian EA, Arad M, Argirò A, Brambatti M, Bui Q, et al. International Consensus on Differential Diagnosis and Management of Patients With Danon Disease: JACC State-of-the-Art Review. J Am Coll Cardiol [Internet]. 2023 Oct 17 [cited 2025 Jan 25];82(16):1628–47. Available from: https://pubmed.ncbi.nlm.nih.gov/37821174/ Charron P, Villard E, Sébillon P, Laforêt P, Maisonobe T, Duboscq-Bidot L, et al. Danon’s disease as a cause of hypertrophic cardiomyopathy: a systematic survey. Heart [Internet]. 2004 Aug [cited 2025 Jan 25];90(8):842–6. Available from: https://pubmed.ncbi.nlm.nih.gov/15253947/ RS D, C L, D S, SL G, LA A, E A, et al. Danon disease: clinical features, evaluation, and management. Circ Heart Fail [Internet]. 2014 Mar 22 [cited 2025 Jan 25];7(5):269–76. Available from: https://pubmed.ncbi.nlm.nih.gov/25228319/ Cottinet SL, Bergemer-Fouquet AM, Toutain A, Sabourdy F, Maakaroun-Vermesse Z, Levade T, et al. Danon disease: intrafamilial phenotypic variability related to a novel LAMP-2 mutation. J Inherit Metab Dis [Internet]. 2011 Apr [cited 2025 Jan 25];34(2):515–22. Available from: https://pubmed.ncbi.nlm.nih.gov/21161685/ Cheng Z, Cui Q, Tian Z, Xie H, Chen L, Fang L, et al. Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy. Eur Heart J [Internet]. 2012 Mar [cited 2025 Jan 25];33(5):649–56. Available from: https://pubmed.ncbi.nlm.nih.gov/22108829/ Lotan D, Salazar-Mendiguchía J, Mogensen J, Rathore F, Anastasakis A, Kaski J, et al. Clinical Profile of Cardiac Involvement in Danon Disease: A Multicenter European Registry. Circ Genom Precis Med [Internet]. 2020 Nov 5 [cited 2025 Jan 25];13(6):e003117–e003117. Available from: https://europepmc.org/article/med/33151750 Boucek D, Jirikowic J, Taylor M. Natural history of Danon disease. Genet Med [Internet]. 2011 Jun [cited 2025 Jan 25];13(6):563–8. Available from: https://pubmed.ncbi.nlm.nih.gov/21415759/ Lotan D, Salazar-Mendiguchía J, Mogensen J, Rathore F, Anastasakis A, Kaski J, et al. Clinical Profile of Cardiac Involvement in Danon Disease: A Multicenter European Registry. Circ Genom Precis Med [Internet]. 2020 Dec 1 [cited 2025 Jan 25];13(6):E003117. Available from: https://pubmed.ncbi.nlm.nih.gov/33151750/ Sugie K, Yamamoto A, Murayama K, Oh SJ, Takahashi M, Mora M, et al. Clinicopathological features of genetically confirmed Danon disease. Neurology [Internet]. 2002 Jun 25 [cited 2025 Jan 25];58(12):1773–8. Available from: https://pubmed.ncbi.nlm.nih.gov/12084876/ GÜLTEKİN N, KÜÇÜKATEŞ E, KOCABAŞ GÜ, ÖZCAN ME. Danon Hastalığı: Klinik Özellikler, Tanı ve Kalp Tutulumu. Türkiye Klinikleri Kardiyoloji - Özel Konular [Internet]. 2018 [cited 2025 Jan 25];11(3):42–50. Available from: https://www.turkiyeklinikleri.com/article/tr-danon-hastaligi-klinik-ozellikler-tani-ve-kalp-tutulumu-82618.html Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 06 Jan, 2026 Reviewers invited by journal 06 Jan, 2026 Editor assigned by journal 05 Jan, 2026 Editor invited by journal 18 Dec, 2025 Submission checks completed at journal 17 Dec, 2025 First submitted to journal 17 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8310373","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":570780262,"identity":"cf76f309-17ac-4b92-959e-e62027e7d34e","order_by":0,"name":"Ramazan Anıl Eşki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYJCCAw8YGAzY2BuATAMLIrUkgLTwHABpkSDSGpAWBokEEJMILebtZw8eSKioM+aTfH51w48CCQb+9u4EvFpkzuQlHEg4c9iMTTqn7GYP0GESZ85uwKtFgiHH4EBi2wEboJa0GzxALQYSuQS08L8BavlXZ8MmeSbt5h+itEiAbGlgNmOTYD92mzhbJIC2JBw7bMzGk8N2W8ZAgoewX/hzjD98qKkznN9+/NnNN39s5Pjbe/FrQQI8BmCSWOUgwP6AFNWjYBSMglEwggAAUuJFLYw6y78AAAAASUVORK5CYII=","orcid":"","institution":"Afyonkarahisar Sağlık Bilimleri Üniversitesi","correspondingAuthor":true,"prefix":"","firstName":"Ramazan","middleName":"Anıl","lastName":"Eşki","suffix":""},{"id":570780263,"identity":"77c0ceba-6572-4325-a0ae-4f403d7aacec","order_by":1,"name":"Cem Korucu","email":"","orcid":"","institution":"Afyonkarahisar Sağlık Bilimleri Üniversitesi","correspondingAuthor":false,"prefix":"","firstName":"Cem","middleName":"","lastName":"Korucu","suffix":""},{"id":570780264,"identity":"d370197d-6ff3-4af6-995e-f0f1e922055c","order_by":2,"name":"Zafer Yalım","email":"","orcid":"","institution":"Afyonkarahisar Sağlık Bilimleri Üniversitesi","correspondingAuthor":false,"prefix":"","firstName":"Zafer","middleName":"","lastName":"Yalım","suffix":""}],"badges":[],"createdAt":"2025-12-08 18:23:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8310373/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8310373/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100004506,"identity":"e299c675-994c-4726-8940-f0a21733fe43","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":275708,"visible":true,"origin":"","legend":"","description":"","filename":"ECG300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/85df17a5ade7d31b1744a95e.png"},{"id":100360640,"identity":"2f9e7f4b-b91f-44f9-b83f-8fb70d4b9acb","added_by":"auto","created_at":"2026-01-16 07:40:34","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":23977,"visible":true,"origin":"","legend":"","description":"","filename":"ararecauseofcardachypertrophydanondsease17.12.25.docx","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/3407a12483f2a96107b1dd28.docx"},{"id":100004504,"identity":"8d75f163-cfc0-4d80-a44e-2a9242eae9b8","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":29888,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3Pedigree300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/52dae9b3240153ecc2e30228.png"},{"id":100004508,"identity":"aec92bc3-9d29-4a47-820e-d258edd9c085","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":376865,"visible":true,"origin":"","legend":"","description":"","filename":"TTE300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/106d00f12b4f122d9a052dcd.png"},{"id":100004522,"identity":"2414d7fb-ef90-46e4-b1f1-89afe45ccfcb","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"json","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4754,"visible":true,"origin":"","legend":"","description":"","filename":"23e407c972e64a47819dece11cd47c54.json","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/04ccb9a3ce666658e773d044.json"},{"id":100004509,"identity":"6530c563-ae3c-444f-af25-b4a2c926c426","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":33078,"visible":true,"origin":"","legend":"","description":"","filename":"23e407c972e64a47819dece11cd47c541enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/b24119315f786231ec5cfbfa.xml"},{"id":100004521,"identity":"562beca1-03c3-43c7-96e2-51b738607a45","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":275708,"visible":true,"origin":"","legend":"","description":"","filename":"ECG300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/53ac1c07d80d2aa2e56f9f4c.png"},{"id":100004526,"identity":"a72bf69e-0aff-4884-95cd-6ab6da4467a8","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":29888,"visible":true,"origin":"","legend":"","description":"","filename":"Figure3Pedigree300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/8aed8f60a5c1ee940cab7dfa.png"},{"id":100361274,"identity":"21c2cf61-64f1-4939-9c4f-7f07d6313277","added_by":"auto","created_at":"2026-01-16 07:44:50","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":376865,"visible":true,"origin":"","legend":"","description":"","filename":"TTE300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/4c3e8ba7f941034c67212620.png"},{"id":100004520,"identity":"fa0398c8-76a6-4451-84f7-1314de5ef909","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38521,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineECG300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/5fd82827f21f4080ca174a94.png"},{"id":100004525,"identity":"ebfadfd0-b4ca-4ace-b885-3cf33b8dacd4","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":6003,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineFigure3Pedigree300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/9ebf214d02a5c0b095926290.png"},{"id":100004523,"identity":"5155df6b-a260-4ded-ad78-56f42d1c8cf3","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":45189,"visible":true,"origin":"","legend":"","description":"","filename":"OnlineTTE300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/bb1f27cbd0131ac678c08c07.png"},{"id":100360689,"identity":"401109cc-7a08-4914-a15b-14b62446e3fc","added_by":"auto","created_at":"2026-01-16 07:41:08","extension":"xml","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":31434,"visible":true,"origin":"","legend":"","description":"","filename":"23e407c972e64a47819dece11cd47c541structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/db1cac1f3b0bae856c42b8bf.xml"},{"id":100361288,"identity":"17232ca6-9a5f-46b6-b449-47f0943bae61","added_by":"auto","created_at":"2026-01-16 07:44:50","extension":"html","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38180,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/056c3e0c011a5725424fd93a.html"},{"id":100360669,"identity":"f114f775-d754-4616-a709-bbf769b13f04","added_by":"auto","created_at":"2026-01-16 07:40:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":275708,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eElectrocardiogram at presentation\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"ECG300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/316d9b03497c3e802ef5ca6c.png"},{"id":100004505,"identity":"42543ef7-b869-48b4-8ec2-9e813e15e801","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":376865,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTransthoracic echocardiography\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"TTE300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/87ffd5812d65409dccd39767.png"},{"id":100004514,"identity":"1e044ae3-6718-4210-9dd9-504179da9bc8","added_by":"auto","created_at":"2026-01-12 05:26:22","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":29888,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePedigree analysis\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure3Pedigree300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/0f73ca489fbf4af357a64754.png"},{"id":100380907,"identity":"7e1675b3-23ff-45aa-adf0-387732ed5ee3","added_by":"auto","created_at":"2026-01-16 10:36:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1231303,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8310373/v1/887912d8-2333-4c8d-ba0d-4223cc58f674.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eA Rare Cause of Cardiac Hypertrophy: Danon Disease\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eDanon disease was first described in 1981 in male members of a family presenting with proximal muscle weakness and concomitant myocardial hypertrophy (1). Limited studies in patients with hypertrophic cardiomyopathy (HCM) have reported Danon disease prevalence rates of 4\u0026ndash;6% in pediatric patients, 0.7\u0026ndash;4% in adults with HCM, 6\u0026ndash;8% in adults with symmetric HCM, and 17\u0026ndash;30% in patients with HCM accompanied by pre-excitation (2). The disease is caused by confirmed mutations in the LAMP2 gene (Xq24\u0026ndash;q25), leading to loss of LAMP-2 protein expression. More than 60 pathogenic variants have been identified to date (3).\u003c/p\u003e \u003cp\u003eLAMP-2 deficiency results in impaired lysosomal degradation and accumulation of autophagic material within cells. This leads to mitochondrial oxidative stress, increased apoptosis, altered metabolic pathways, and reduced calcium handling, ultimately causing contractile dysfunction (4). Although Danon disease is an important cause of cardiac hypertrophy, numerous other etiologies must also be considered. Besides common causes such as hypertension, valvular disease, and age-related changes, cardiac amyloidosis\u0026mdash;particularly in elderly patients\u0026mdash;should remain an important differential diagnosis.\u003c/p\u003e \u003cp\u003eIn this case report, we present a rare coexistence of Danon disease and cardiac amyloidosis in a woman with left ventricular hypertrophy and heterogeneous clinical features.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"CASE PRESENTATION","content":"\u003cp\u003eA 64-year-old woman presented with exertional dyspnea, palpitations, hand paresthesia, and fatigue. She denied chest pain, syncope, learning difficulties, cognitive impairment, or visual disturbances. Her symptoms had progressively worsened in recent months. Past medical history included hypertension, diabetes mellitus, asthma, chronic venous insufficiency, deep vein thrombosis, cervical disc herniation, bilateral carpal tunnel syndrome, and vertigo. There was no family history of sudden cardiac death. Neuromuscular examination revealed no significant muscle weakness.\u003c/p\u003e \u003cp\u003eHer medications included: acetylsalicylic acid 100 mg daily, valsartan 160 mg\u0026thinsp;+\u0026thinsp;hydrochlorothiazide 12.5 mg daily, trimetazidine 35 mg twice daily, colchicine 0.5 mg twice daily, calcium dobesilate 500 mg twice daily, alpha-lipoic acid 600 mg daily, desloratadine/montelukast daily, inhaled salmeterol/fluticasone, metformin 1000 mg twice daily, and famotidine 40 mg daily.\u003c/p\u003e \u003cp\u003eElectrocardiography (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) revealed sinus rhythm with a heart rate of 68 bpm, PR interval of 230 ms, and first-degree atrioventricular block. Blood pressure was 125/75 mmHg. Peripheral pulses were palpable, and findings of venous insufficiency were present.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eEchocardiography (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) showed an ejection fraction of 60%, interventricular septal thickness of 15 mm, posterior wall thickness of 13 mm, LVEDD 45 mm, LVESD 23 mm, and mild mitral and tricuspid regurgitation. Pulmonary artery systolic pressure was 30 mmHg. Diastolic function parameters included E/A: 0.8, E/E\u0026prime;: 10.5, lateral annular S\u0026prime;: 6 cm/s, E\u0026prime;: 6.7 cm/s, and A\u0026prime;: 11.2 cm/s. LVOT gradient was within normal limits.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eLaboratory evaluation revealed elevated pro-BNP (767.4 ng/L), while renal and hepatic markers were within normal range except for mild LDH elevation.\u003c/p\u003e \u003cp\u003eGiven the presence of left ventricular hypertrophy, diastolic dysfunction, and bilateral carpal tunnel syndrome, cardiac amyloidosis was strongly suspected. Bone scintigraphy (Tc-PYP) demonstrated Grade 2 myocardial uptake. Serum/urine electrophoresis and serum free light chain analysis excluded monoclonal gammopathy. Genetic testing identified a heterozygous LAMP2 (NM_002294) c.755T\u0026thinsp;\u0026gt;\u0026thinsp;C (p.I252T) variant, confirming Danon disease. Pedigree analysis identified the same mutation in her children and siblings (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHolter monitoring revealed no significant arrhythmias. The patient was referred to neurology, ophthalmology, and physical medicine departments for multidisciplinary follow-up alongside cardiology.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eDanon disease was originally categorized in 1981 as an X-linked glycogen storage disorder presenting with cardiomyopathy, mental retardation, and myopathy, initially distinguished from Pompe disease due to normal acid maltase levels (1). In 2000, Nishino et al. identified LAMP2 mutations as the underlying cause of the disease through impaired lysosomal function (5). It manifests as severe multisystem involvement, typically with hypertrophic cardiomyopathy, skeletal myopathy, and cognitive deficits in males, whereas females often show milder phenotypes (6). More than one-third of cases arise from de novo mutations (7).\u003c/p\u003e \u003cp\u003eThe global HCM prevalence is approximately 0.2%, and Danon disease accounts for ~\u0026thinsp;1% of index HCM cases, 3% of non-sarcomeric HCM cases, and 4% of genetically analyzed cohorts (8). Thus, Danon disease should always be considered\u0026mdash;particularly in atypical or severe hypertrophic phenotypes.\u003c/p\u003e \u003cp\u003eLAMP2 deficiency results in impaired autophagosome-lysosome fusion, accumulation of dysfunctional mitochondria, metabolic impairment, and oxidative stress (9\u0026ndash;11). Diagnosis relies on genetic confirmation, although biopsy may demonstrate cytoplasmic vacuoles containing autophagic material and glycogen.\u003c/p\u003e \u003cp\u003eOur case demonstrates the heterogeneous clinical spectrum within the same family; although our patient exhibited significant hypertrophy and symptomatic burden, her son showed only mild hypertrophy. Female carriers often display variable phenotypes due to differences in X-chromosome inactivation (12). In our patient, diagnosis was made at a relatively advanced age, which is less typical but reported in the literature.\u003c/p\u003e \u003cp\u003eCardiac involvement occurs in 96% of patients and is the major determinant of prognosis. While males typically exhibit hypertrophic cardiomyopathy, females may present with either hypertrophic (33%) or dilated (28%) patterns (13). Pre-excitation (WPW pattern) is common, found in up to 69% of cases (13,15), while arrhythmias\u0026mdash;including atrial fibrillation, supraventricular tachycardias, and ventricular arrhythmias\u0026mdash;occur in approximately 60% of individuals. Conduction disease (high-degree AV block, sinus node dysfunction) is also frequent (7). In contrast, our patient exhibited only a first-degree AV block.\u003c/p\u003e \u003cp\u003eSkeletal myopathy manifests as progressive proximal weakness but is often mild in females. Cognitive impairment is also more common in males. Our patient and her relatives did not show notable cognitive abnormalities.\u003c/p\u003e \u003cp\u003eManagement requires a multidisciplinary approach. Regular cardiology follow-up with ECG, echocardiography, natriuretic peptides, and Holter monitoring is essential. Cardiac MRI may help identify fibrosis and arrhythmic risk. No disease-specific medical therapy exists; treatment is aimed at managing heart failure and arrhythmias. β-blockers, diuretics, and antiarrhythmics may be used as indicated. ICD implantation should be considered in patients with significant hypertrophy, fibrosis, symptomatic arrhythmias, or a family history of sudden cardiac death. Advanced therapies\u0026mdash;including transplantation and electrophysiological interventions\u0026mdash;may be required.\u003c/p\u003e \u003cp\u003eIn our case, the additional presence of Grade 2 myocardial uptake suggesting transthyretin amyloidosis represents a rare and clinically challenging scenario. There is limited evidence on the coexistence of Danon disease and amyloidosis, and decisions regarding amyloidosis-specific therapy remain individualized.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eDanon disease should be considered in the differential diagnosis of unexplained left ventricular hypertrophy, even in older female patients and in the presence of features suggestive of cardiac amyloidosis. Genetic evaluation plays a pivotal role in diagnosis, and family screening is essential. The coexistence of Danon disease and cardiac amyloidosis, as in our patient, underscores the importance of comprehensive clinical evaluation and multidisciplinary management.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eatrioventricular\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eECG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eelectrocardiography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eejection fraction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHCM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehypertrophic cardiomyopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVSd\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einterventricular septal thickness in diastole\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLAMP2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elysosome-associated membrane protein-2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft ventricle\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVEDD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft ventricular end-diastolic diameter\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVESD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eleft ventricular end-systolic diameter\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePABs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epulmonary artery systolic pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePR interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTc-PYP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etechnetium-99m pyrophosphate.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003eNot applicable. Ethics committee approval was not required for this case report according to the policies of our institution.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003e Written informed consent was obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo funding was received for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eRamazan Anıl Eşki evaluated and examined the patient during the initial clinical presentation and collected the clinical data. Cem Korucu performed and interpreted the echocardiographic and imaging assessments. Zafer Yalım supervised the diagnostic process, contributed to the clinical interpretation of findings, and guided the planning and development of the manuscript. All authors contributed to the drafting and critical revision of the manuscript, approved the final version, and agree to be accountable for all aspects of the work.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eNot applicable. All relevant data are included within the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDanon MJ, Oh SJ, DiMauro S, Manaligod JR, Eastwood A, Naidu S, et al. Lysosomal glycogen storage disease with normal acid maltase. Neurology [Internet]. 1981 [cited 2025 Jan 23];31(1):51\u0026ndash;7. Available from: https://pubmed.ncbi.nlm.nih.gov/6450334/\u003c/li\u003e\n\u003cli\u003eWang Y, Jia M, Guo Y, Zhang T, Ning B. Case Report: Danon Disease: Six Family Members and Literature Review. Front Cardiovasc Med [Internet]. 2022 May 20 [cited 2025 Jan 23];9:842282. Available from: www.frontiersin.org\u003c/li\u003e\n\u003cli\u003eCheng Z, Fang Q. Danon disease: focusing on heart. J Hum Genet [Internet]. 2012 Jul [cited 2025 Jan 25];57(7):407\u0026ndash;10. Available from: https://pubmed.ncbi.nlm.nih.gov/22695892/\u003c/li\u003e\n\u003cli\u003eChi C, Leonard A, Knight WE, Beussman KM, Zhao Y, Cao Y, et al. LAMP-2B regulates human cardiomyocyte function by mediating autophagosome\u0026ndash;lysosome fusion. Proc Natl Acad Sci U S A. 2019 Jan 8;116(2):556\u0026ndash;65. \u003c/li\u003e\n\u003cli\u003eNishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T, et al. Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature [Internet]. 2000 Aug 24 [cited 2025 Jan 25];406(6798):906\u0026ndash;10. Available from: https://pubmed.ncbi.nlm.nih.gov/10972294/\u003c/li\u003e\n\u003cli\u003eCenacchi G, Papa V, Pegoraro V, Marozzo R, Fanin M, Angelini C. Review: Danon disease: Review of natural history and recent advances. Neuropathol Appl Neurobiol [Internet]. 2020 Jun 1 [cited 2025 Jan 25];46(4):303\u0026ndash;22. Available from: https://pubmed.ncbi.nlm.nih.gov/31698507/\u003c/li\u003e\n\u003cli\u003eHong KN, Eshraghian EA, Arad M, Argir\u0026ograve; A, Brambatti M, Bui Q, et al. International Consensus on Differential Diagnosis and Management of Patients With Danon Disease: JACC State-of-the-Art Review. J Am Coll Cardiol [Internet]. 2023 Oct 17 [cited 2025 Jan 25];82(16):1628\u0026ndash;47. Available from: https://pubmed.ncbi.nlm.nih.gov/37821174/\u003c/li\u003e\n\u003cli\u003eCharron P, Villard E, S\u0026eacute;billon P, Lafor\u0026ecirc;t P, Maisonobe T, Duboscq-Bidot L, et al. Danon\u0026rsquo;s disease as a cause of hypertrophic cardiomyopathy: a systematic survey. Heart [Internet]. 2004 Aug [cited 2025 Jan 25];90(8):842\u0026ndash;6. Available from: https://pubmed.ncbi.nlm.nih.gov/15253947/\u003c/li\u003e\n\u003cli\u003eRS D, C L, D S, SL G, LA A, E A, et al. Danon disease: clinical features, evaluation, and management. Circ Heart Fail [Internet]. 2014 Mar 22 [cited 2025 Jan 25];7(5):269\u0026ndash;76. Available from: https://pubmed.ncbi.nlm.nih.gov/25228319/\u003c/li\u003e\n\u003cli\u003eCottinet SL, Bergemer-Fouquet AM, Toutain A, Sabourdy F, Maakaroun-Vermesse Z, Levade T, et al. Danon disease: intrafamilial phenotypic variability related to a novel LAMP-2 mutation. J Inherit Metab Dis [Internet]. 2011 Apr [cited 2025 Jan 25];34(2):515\u0026ndash;22. Available from: https://pubmed.ncbi.nlm.nih.gov/21161685/\u003c/li\u003e\n\u003cli\u003eCheng Z, Cui Q, Tian Z, Xie H, Chen L, Fang L, et al. Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy. Eur Heart J [Internet]. 2012 Mar [cited 2025 Jan 25];33(5):649\u0026ndash;56. Available from: https://pubmed.ncbi.nlm.nih.gov/22108829/\u003c/li\u003e\n\u003cli\u003eLotan D, Salazar-Mendiguch\u0026iacute;a J, Mogensen J, Rathore F, Anastasakis A, Kaski J, et al. Clinical Profile of Cardiac Involvement in Danon Disease: A Multicenter European Registry. Circ Genom Precis Med [Internet]. 2020 Nov 5 [cited 2025 Jan 25];13(6):e003117\u0026ndash;e003117. Available from: https://europepmc.org/article/med/33151750\u003c/li\u003e\n\u003cli\u003eBoucek D, Jirikowic J, Taylor M. Natural history of Danon disease. Genet Med [Internet]. 2011 Jun [cited 2025 Jan 25];13(6):563\u0026ndash;8. Available from: https://pubmed.ncbi.nlm.nih.gov/21415759/\u003c/li\u003e\n\u003cli\u003eLotan D, Salazar-Mendiguch\u0026iacute;a J, Mogensen J, Rathore F, Anastasakis A, Kaski J, et al. Clinical Profile of Cardiac Involvement in Danon Disease: A Multicenter European Registry. Circ Genom Precis Med [Internet]. 2020 Dec 1 [cited 2025 Jan 25];13(6):E003117. Available from: https://pubmed.ncbi.nlm.nih.gov/33151750/\u003c/li\u003e\n\u003cli\u003eSugie K, Yamamoto A, Murayama K, Oh SJ, Takahashi M, Mora M, et al. Clinicopathological features of genetically confirmed Danon disease. Neurology [Internet]. 2002 Jun 25 [cited 2025 Jan 25];58(12):1773\u0026ndash;8. Available from: https://pubmed.ncbi.nlm.nih.gov/12084876/\u003c/li\u003e\n\u003cli\u003eG\u0026Uuml;LTEKİN N, K\u0026Uuml;\u0026Ccedil;\u0026Uuml;KATEŞ E, KOCABAŞ G\u0026Uuml;, \u0026Ouml;ZCAN ME. Danon Hastalığı: Klinik \u0026Ouml;zellikler, Tanı ve Kalp Tutulumu. T\u0026uuml;rkiye Klinikleri Kardiyoloji - \u0026Ouml;zel Konular [Internet]. 2018 [cited 2025 Jan 25];11(3):42\u0026ndash;50. Available from: https://www.turkiyeklinikleri.com/article/tr-danon-hastaligi-klinik-ozellikler-tani-ve-kalp-tutulumu-82618.html\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Danon disease, LAMP2 gene, cardiac hypertrophy, cardiac amyloidosis","lastPublishedDoi":"10.21203/rs.3.rs-8310373/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8310373/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCardiac hypertrophy is a common clinical finding and may appear as a cardiac manifestation of numerous diseases. In addition to frequently encountered causes such as hypertension and valvular heart disease, clinicians must also consider cardiac amyloidosis, hypertrophic cardiomyopathies, and various rare genetic conditions. Danon disease is a rare X-linked dominant multisystem disorder characterized by cardiomyopathy, skeletal myopathy, and intellectual disability. It results from defects in the lysosome-associated membrane protein-2 (LAMP2) gene, and numerous pathogenic mutations have been described.\u003c/p\u003e \u003cp\u003eHere, we present the case of a 64-year-old woman who was evaluated for suspected cardiac amyloidosis due to marked left ventricular hypertrophy and was subsequently diagnosed with Danon disease. The coexistence of Danon disease and cardiac amyloidosis is exceedingly uncommon and highlights the importance of considering rare etiologies in patients presenting with hypertrophic phenotypes.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e","manuscriptTitle":"A Rare Cause of Cardiac Hypertrophy: Danon Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-12 05:26:17","doi":"10.21203/rs.3.rs-8310373/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"9868748736812434045531493267699102071","date":"2026-01-06T14:19:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-06T12:31:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-05T08:17:11+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-18T07:09:28+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-17T18:14:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-12-17T17:42:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d6fecf6d-26d8-4a9c-ba67-2dfc5e388f64","owner":[],"postedDate":"January 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T05:26:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-12 05:26:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8310373","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8310373","identity":"rs-8310373","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}