Easily Misdiagnosed cblC Deficiency in Adolescents: the Clinical and Metabolic Studies

Purpose: Adolescents are easily attacked by potential inherited metabolic disorders. cblC deficiency is the most common type of methylmalonic aciduria in China. The late-onset patients present with varied non-specific symptoms and usually being misdiagnosed. The purpose of this study is to investigate the clinical features of patients with adolescence-onset cblC deficiency and explore the prevention and control strategies. Methods: Fifty-seven patients (34 males and 23 females) with adolescence-onset cblC deficiency were admitted in our clinic from 2002 to September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome and genotypes-phenotypes correlation were examined. Results: The onset ages ranged from 10 to 25 years old (median age was 12 years). 16 cases (28.0%) presented with symptoms after infection or sports training. 46 patients (80.7%) had neuropsychiatric diseases. 14 patients (24.6%) displayed cardiovascular diseases. Five cases (8.9%) showed pulmonary hypertension. Renal damage was observed in seven cases (12.3%). 23 mutations were identified from the MMACHC gene of 57 patients. 37 patients demonstrated c.482G>A (64.9%) and 16 cases had c.609G>A (26.3%). Among 13 patients that exhibited spastic paraplegia as a main manifestation, 10 patients had c.482G>A (76.9%). Five patients presented with psychotic disorders and spastic paraplegia with c.482G>A. All patients improved after metabolic treatment with cobalamin, L-carnitine, and betaine. 30 school-aged patients returned to school. Two patients were married and had healthy babies. Conclusion: Patients with adolescence-onset cblC deficiency presented with varied neuropsychiatric symptoms or multiple organ damage. Metabolic studies and individualized treatment are keys to improve the outcome of the patients.