Fumarase deficiency: two siblings with enlarged cerebral ventricles and polyhydramnios in utero

Pediatrics. 1992 Apr;89(4 Pt 2):730-4.


A family having two boys with progressive encephalomyopathy and fumaric aciduria due to fumarase deficiency is described. Both patients initially presented with polyhydramnios and enlarged cerebral ventricles in utero, with subsequent cerebral atrophy, severe developmental delay, infantile spasms, and hypsarythmia on electroencephalogram. Fumarase activity in blood mononuclear cells and in the mitochondrial and cytosolic fractions of cultured skin fibroblasts was less than 0.5% of the control mean or undetectable. The older boy died at the age of 5 years and 4 months and the younger one is now 2 years and 10 months. The unrelated parents are symptomless and the other three children in the family are clinically healthy. Fumarase activities in the blood mononuclear cells of the father, mother, sister, and two brothers were 59%, 52%, 52%, 120%, and 44% of the control mean, respectively. The results strongly support autosomal recessive inheritance of fumarase deficiency and suggest its consideration in children with congenital hydrocephalus, progressive brain atrophy, and infantile spasms.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Cells, Cultured / enzymology
  • Cerebral Ventriculography
  • Child, Preschool
  • Electroencephalography
  • Fibroblasts / enzymology
  • Fumarate Hydratase / deficiency*
  • Fumarates / urine
  • Humans
  • Hydrocephalus / diagnosis*
  • Hydrocephalus / genetics
  • Hydrocephalus / metabolism
  • Male
  • Polyhydramnios / diagnosis*
  • Polyhydramnios / metabolism
  • Skin / enzymology
  • Tomography, X-Ray Computed


  • Fumarates
  • fumaric acid
  • Fumarate Hydratase