Dihydrolipoamide dehydrogenase deficiency in two unrelated Tunisian children

Dihydrolipoamide dehydrogenase deficiency (DLDD) (OMIM# 246,900) is an extremely rare inherited metabolic disorder causing neurological and/or liver impairment. The clinical manifestations are mostly characterized by severe neurological impairment in early childhood, hepatic presentations and rarely by myopathic manifestations.

Here, we describe two patients presenting with recurrent episodes of vomiting and liver dysfunction. DLDD was confirmed via sanger sequencing by identification of the pathogenic variant c.685G > T (p.Gly229Cys) in DLD gene at a homozygous state.

To our knowledge, this is the first Tunisian report of DLDD. Phenotypic spectrum of this disease is very large. Biochemical markers that predict the impairment of the pathways affected by the deficiency of E3 subunit (gluconeogenesis, tricyclic cycle and catabolism of branched chain aminoacids) are variably present. Confirmation is based on genetic study of DLD gene.