Fumarase Deficiency (FH)
Fumarase deficiency is an autosomal recessive, pan-ethnic disorder caused by pathogenic variants in the gene FH. Onset is at birth. Clinical features include brain malformations and severe psychomotor delays. Most patients will never learn to sit or crawl. Patients also have poor feeding, failure to thrive, hypotonia, seizures, and facial dysmorphism. Most patients die in infancy or early childhood. Those that survive early childhood are usually severely disabled. Several patients have been identified with a milder form of the disease; these patients exhibit moderate cognitive impairment and longer survival. It is not currently possible to predict the severity of the disease based on the inherited variants. Heterozygous carriers of a pathogenic FH variant have an increased risk of developing benign cutaneous leiomyomas, uterine leiomyomas and/or uterine fibroids. Compared to the general population, carriers also have an increased risk of developing cancer of the kidney.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.