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Fumarase deficiency: two siblings with enlarged cerebral ventricles and polyhydramnios in utero
A M Remes1, H Rantala, J K Hiltunen
1Department of Medical Biochemistry, University of Oulu, Finland.
Insights
Fumarase deficiency, a genetic disorder, causes severe neurological issues in children, including developmental delay and brain atrophy. This study supports its autosomal recessive inheritance pattern.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Fumarase deficiency is a rare metabolic disorder.
- It is associated with progressive encephalomyopathy and fumaric aciduria.
- Understanding its inheritance pattern is crucial for genetic counseling.
Observation:
- A family with two affected boys presented with severe congenital neurological abnormalities.
- Patients exhibited polyhydramnios, enlarged cerebral ventricles, cerebral atrophy, developmental delay, and infantile spasms.
- Enzyme assays revealed undetectable fumarase activity in affected individuals.
Findings:
- Fumarase activity was significantly reduced in affected boys, with levels below 0.5% of controls.
- Enzyme activity in parents and healthy siblings showed variable but generally reduced levels, supporting carrier status.
- The pattern of inheritance in the described family strongly suggests an autosomal recessive mode for fumarase deficiency.
Implications:
- Fumarase deficiency should be considered in the differential diagnosis of congenital hydrocephalus and severe infantile encephalomyopathy.
- Early diagnosis and genetic counseling are vital for families with a history of fumarase deficiency.
- This research reinforces the link between fumarase deficiency and severe neurodevelopmental outcomes.
Abstract:
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.