Clinical, Biochemical, and Molecular Characterization of Two Families with Novel Mutations in the LDHA Gene (GSD XI)

Genes (Basel). 2022 Oct 11;13(10):1835. doi: 10.3390/genes13101835.

Abstract

Lactate dehydrogenase (LDH) catalyzes the reversible conversion of L-lactate to pyruvate. LDH-A deficiency is an autosomal recessive disorder (glycogenosis type XI, OMIM#612933) caused by mutations in the LDHA gene. We present two young adult female patients presenting with intolerance to anaerobic exercise, episodes of rhabdomyolysis, and, in one of the patients, psoriasis-like dermatitis. We identified in the LDHA gene a homozygous c.410C>A substitution that predicts a p.Ser137Ter nonsense mutation in Patient One and a compound heterozygous c.410C>A (p.Ser137Ter) and c.750G>A (p.Trp250Ter) nonsense mutation in Patient Two. The pathogenicity of the variants was demonstrated by electrophoretic separation of LDH isoenzymes. Moreover, a flat lactate curve on the forearm exercise test, along with the clinical combination of myopathy and psoriatic-like dermatitis, can also lead to the diagnosis.

Keywords: LDH isoenzymes; LDHA gene; lactate dehydrogenase (LDH); lactate dehydrogenase A deficiency; myopathy and psoriatic dermatitis.

Publication types

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

MeSH terms

  • Codon, Nonsense
  • Dermatitis*
  • Female
  • Glycogen Storage Disease*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Lactate Dehydrogenase 5
  • Lactic Acid / metabolism
  • Mutation
  • Pyruvic Acid

Substances

  • Lactate Dehydrogenase 5
  • Isoenzymes
  • Codon, Nonsense
  • Lactic Acid
  • Pyruvic Acid

Supplementary concepts

  • Lactate dehydrogenase deficiency type A

Grants and funding

Projects PI17_02052 to J.A. and PI21_00381 to M.A.M., funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union. P.S.-L. is supported by an ISCIII-CIBERER contract.