A fatal case of neonatal onset multiple Acyl-CoA dehydrogenase deficiency caused by novel mutation of ETFDH gene: case report.

Background: Multiple acyl-CoA dehydrogenase deficiency (MADD) or glutaric aciduria type II is an extremely rare autosomal recessive inborn error of fatty acid beta oxidation and branched-chain amino acids, secondary to mutations in the genes encoding the electron transfer flavoproteins A and B (ETFs; ETFA or ETFB) or ETF dehydrogenase (ETFDH). The clinical manifestation of MADD is heterogeneous, from severe neonatal forms to mild late-onset forms.Case presentation. We report the case of a preterm newborn who died a few days after birth for an untreatable condition of metabolic acidosis. The diagnosis of neonatal onset MADD was suggested on the basis of the clinical features displaying congenital abnormalities and of the results of the analysis of urinary organic acids along with plasma amino acids and acylcarnitines. Molecular genetic test revealed a homozygous indel variant c.606 + 1 _606 + 2insT in the ETFDH gene, localized in a canonical splite site. This variant, segregated from the two heterozygous parents, was not present in the general population frequency database and has never been reported in the literature.Discussion and conclusion. Genetic counselling should be offered to parents to inform them about the percentage of risk to have an affected child in case of a new pregnancy and about the possibility to perform, in such circumstance, prenatal molecular genetic testing.