Fumarase Deficiency: A Case With a New Pathogenic Mutation and a Review of the Literature

J Child Neurol. 2021 Mar;36(4):310-323. doi: 10.1177/0883073820962931. Epub 2020 Oct 14.


Fumarase deficiency (FD) is a rare and severe autosomal disorder, caused by inactivity of the enzyme fumarase, due to biallelic mutations of the fumarase hydratase (FH) gene. Several pathogenic mutations have been published. The article describes an infant with failure to thrive, microcephaly, axial hypotonia, and developmental retardation with increased excretion of fumarate, no activity of fumarase and a homozygous mutation of the FH gene, which was until recently only known as a variant of unknown significance. Carriers of pathogenic mutations in the FH gene are at risk for developing renal cell carcinoma and should therefore be screened. Both parents were healthy carriers of the mutation and had decreased levels of enzyme activity. In addition, the article presents an overview and analysis of all cases of FD reported thus far in the literature.

Keywords: FH gene; Fumarase deficiency; literature review; mutation.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Fumarate Hydratase / deficiency*
  • Fumarate Hydratase / genetics*
  • Humans
  • Infant
  • Male
  • Metabolism, Inborn Errors / diagnostic imaging
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / pathology*
  • Muscle Hypotonia / diagnostic imaging
  • Muscle Hypotonia / genetics*
  • Muscle Hypotonia / pathology*
  • Psychomotor Disorders / diagnostic imaging
  • Psychomotor Disorders / genetics*
  • Psychomotor Disorders / pathology*


  • Fumarate Hydratase

Supplementary concepts

  • Fumaric aciduria