Rare Diseases Symptoms Automatic Extraction

Pyruvate dehydrogenase deficiency: molecular basis for intrafamilial heterogeneity.

[pyruvate dehydrogenase deficiency]

Two half-brothers and their mother had symptomatic pyruvate dehydrogenase complex deficiency. The infants had severe congenital lactic acidosis, seizures, and apneic spells and died at the ages 3 and 4 months. The mother was less symptomatic with mental retardation, truncal ataxia, and dysarthria. The residual pyruvate dehydrogenase activities in cultured skin fibroblasts from the 2 infants and their mother were 7, 15, and 10% of control values. Immunoblot analysis showed negligible amounts of E1 alpha and E1 beta subunits of the complex. Northern blot analysis for the E1 alpha subunit showed normal results. In the 2 sons, complementary DNA sequence analysis revealed a cytosine to thymine mutation in exon 4, resulting in a change of arginine 127 to tryptophan in the E1 alpha subunit. Restriction enzyme analysis of the polymerase chain reaction product representing exon 4 of the E1 alpha gene revealed that the mother was a heterozygotes. Complementary DNA restriction analysis and methylation analysis of the X chromosome DXS255 loci revealed skewed activation of the mutant allele, consistent with the deficient pyruvate dehydrogenase activity in the mother's fibroblasts. The milder maternal phenotype is consistent with variable X-inactivation patterns in different organs of female heterozygotes.

Diseases presenting "mental retardation" symptom

  • achondroplasia
  • alexander disease
  • alpha-thalassemia
  • aniridia
  • aromatase deficiency
  • canavan disease
  • classical phenylketonuria
  • coats disease
  • cohen syndrome
  • cowden syndrome
  • cystinuria
  • dentin dysplasia
  • familial hypocalciuric hypercalcemia
  • homocystinuria without methylmalonic aciduria
  • hydrocephalus with stenosis of the aqueduct of sylvius
  • kabuki syndrome
  • kallmann syndrome
  • lamellar ichthyosis
  • lymphangioleiomyomatosis
  • monosomy 21
  • phenylketonuria
  • primary hyperoxaluria type 1
  • proteus syndrome
  • pyruvate dehydrogenase deficiency
  • sneddon syndrome
  • triple a syndrome
  • wolf-hirschhorn syndrome
  • zellweger syndrome

This symptom has already been validated