Clinical report and biochemical analysis of a patient with fumarate hydratase deficiency

Am J Med Genet A. 2020 Mar;182(3):504-507. doi: 10.1002/ajmg.a.61415. Epub 2019 Nov 20.

Abstract

Fumarate hydratase deficiency (FHD) is a rare metabolic disease caused by two defective copies of the FH gene, which encodes the Krebs cycle enzyme fumarase. FHD is associated with brain and developmental abnormalities, seizures, and high childhood mortality. We describe the symptoms and treatment of a patient with FHD. While infantile spasms are common in FHD, the patient presented with epileptic spasms later in childhood. Also unexpectedly, the patient responded excellently to lacosamide for her non-convulsive status epilepticus and epileptic spasms after three first-line medication trials failed. We biochemically analyzed the patient's two fumarase variants (E432Kfs*17 and D65G). While E432Kfs*17 was extremely enzymatically defective, D65G exhibited only a mild defect, possibly playing a role in the patient's longer survival.

Keywords: epilepsy; fumarase; fumarate hydratase deficiency; lacosamide; seizure.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / pathology
  • Child
  • Female
  • Fumarate Hydratase / deficiency*
  • Fumarate Hydratase / genetics*
  • Humans
  • Infant, Newborn
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / mortality
  • Muscle Hypotonia / diagnosis
  • Muscle Hypotonia / genetics*
  • Muscle Hypotonia / mortality
  • Mutation / genetics
  • Psychomotor Disorders / diagnosis
  • Psychomotor Disorders / genetics*
  • Psychomotor Disorders / mortality
  • Seizures / diagnosis
  • Seizures / genetics
  • Seizures / mortality
  • Spasms, Infantile / diagnosis
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / mortality

Substances

  • Fumarate Hydratase

Supplementary concepts

  • Fumaric aciduria