identical to Orphanet:79243 "Pyruvate dehydrogenase E1-alpha deficiency;
OMIM:308930 "LEIGH SYNDROME, X-LINKED" now moved to OMIM:312170 "PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY; PDHAD
In a case of acute infantile Leigh syndrome, Matthews et al. (1993) demonstrated a point mutation in the PDHA1 gene (300502.0011). The infant was delivered by cesarean section at 36 weeks because of worsening preeclampsia and a breech ... In a case of acute infantile Leigh syndrome, Matthews et al. (1993) demonstrated a point mutation in the PDHA1 gene (300502.0011). The infant was delivered by cesarean section at 36 weeks because of worsening preeclampsia and a breech presentation. On delivery the infant was limp and apneic. He showed little growth or development and died at about 13 weeks. The pathologic findings were consistent with subacute necrotizing encephalomyelopathy, and deficiency of the pyruvate dehydrogenase complex was demonstrated enzymatically. In a boy with X-linked Leigh syndrome, Naito et al. (1997) identified a mutation in the PDHA1 gene (300502.0022). His unaffected mother was heterozygous for the mutation. The boy was born at term to normal, unrelated parents. At age 4 months, he showed developmental delay. He had increased blood lactate and pyruvate and basal ganglia lesions on MRI. His older brother had shown a similar disorder, with hypotonia, mental retardation, lactic acidemia, and basal ganglia lesions. The brothers died at ages 6 and 4 years, respectively, from respiratory failure. The index patient showed some clinical improvement with thiamine therapy. Functional studies of cells from the patient and his mother showed decreased affinity of the pyruvate dehydrogenase complex, and the E1 subunit in particular, for thiamine pyrophosphate, a necessary coenzyme. Naito et al. (1997) suggested that variable expression of pyruvate dehydrogenase complex deficiencies may depend on surrounding concentrations of thiamine and thiamine pyrophosphate.