Fumarate dehydratase defiency – a rare cause of developmental delay and seizures

Fumarate hydratase deficiency is a rare disorder, described in only 32 cases. The clinical presentation is a severe psychomotor retardation, facial dysmorphism and severe brain malformations. Our patient is a girl born after an uncomplicated pregnancy of unrelated parents. She started to have focal seizures with secondary generalisation at the age of 9 months. She sat a 10 months and crawled at 15 months. At the age of 29 months physical and neurological examination shows a normocephalic child who does not speak and stands with aid. She has a moderate developmental delay and seizures are controlled with anti-epileptic drugs. An MRI of the brain did not reveal any abnormalities. Caryotype was normal. On metabolic screen an increased excretion of fumaric acid was found. Activity of fumarate hydratase in cultured fibroblasts was decreased to 10 % of low border of reference range. Two mutations were founding in the fumarase hydratase gene, one 1078 C to T resulting in a change of a histidine into tyrosine, and one in intron 9 c (A to G) creating new 5' exon recognition site. Organic acid analysis in children with developmental delay and seizures can lead to a rare inborn error of metabolism.