Open AccessThiamine responsive pyruvate dehydrogenase complex deficiency: A potentially treatable cause of Leigh's disease
Author(s) -
Prashant Jauhari,
Naveen Sankhyan,
Sameer Vyas,
Pratibha Singhi
Publication year - 2017
Publication title -
journal of pediatric neurosciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.247
H-Index - 18
eISSN - 1998-3948
pISSN - 1817-1745
DOI - 10.4103/jpn.jpn_191_16
Subject(s) - medicine , leigh disease , pyruvate dehydrogenase complex , missense mutation , thiamine , encephalopathy , endocrinology , hyperammonemia , mitochondrial disease , inborn error of metabolism , pediatrics , mutation , genetics , biochemistry , biology , enzyme , gene , mitochondrial dna
Pyruvate dehydrogenase complex (PDHC) deficiency is a rare metabolic disorder that affects tissues with high energy demand such as the central nervous system. The clinico-radiological phenotype of Leigh's disease is one of its common presentations. We present a 9-month-old boy with rapidly progressive infantile Leigh's disease. PDHA1 gene sequencing revealed a pathological homozygous missense mutation c.131A>G or p.H44R in exon 3 consistent with PDHC deficiency. H44R is among the five mutations (H44R, R88S, G89S, R263G, and V389fs) in E1α subunit that is thiamine-responsive. The child was initiated on thiamine, riboflavin, carnitine, coenzyme Q, and sodium benzoate supplementation. Mild recovery was noted at 6 months follow up as no further episodes of encephalopathy occurred. Thereafter, the child was treated with Ketogenic diet which resulted in increased levels of activity and alertness. Despite an improving course, the child had a sudden unexpected death at the age of 21 months.