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D-2-Hydroxyglutaric aciduria in a patient with a severe clinical phenotype and unusual MRI findings

M Wajne1, C R Vargas, C Funayama

  • 1Medical Genetics Service, Hospital de Clínicas de Porto Alegre, RS, Brazil. mwajner@hcpa.ufrgs.br

Journal of Inherited Metabolic Disease
|May 10, 2002
PubMed

Insights

This study presents a rare case of D-2-hydroxyglutaric aciduria (D-2-OHGA) in an infant with cardiomyopathy. The findings suggest D-2-OHG acid may functionally impair the respiratory chain, leading to metabolic derangements.

Area of Science:

  • Biochemistry
  • Metabolic Disorders
  • Pediatric Neurology

Background:

  • D-2-hydroxyglutaric aciduria (D-2-OHGA) is a rare metabolic disorder.
  • Understanding the precise mechanisms and clinical spectrum of D-2-OHGA is crucial for diagnosis and management.

Observation:

  • An infant presented with hypotonia, seizures, developmental delay, and cardiomyopathy, exhibiting intermittent high urinary D-2-hydroxyglutaric acid (D-2-OHG) and succinic acid levels.
  • Cerebral MRI revealed specific brain lesions suggestive of a mitochondriopathy.
  • Fibroblast studies showed normal respiratory chain enzyme activities but demonstrated inhibition of cytochrome-c oxidase by D-2-OHG acid in vitro.

Findings:

  • The patient exhibited an unusual form of D-2-OHGA.
  • D-2-OHG acid directly inhibited cytochrome-c oxidase activity, suggesting a functional respiratory chain defect.

Implications:

  • This case expands the known clinical and biochemical spectrum of D-2-OHGA.
  • The results propose a novel mechanism where D-2-OHG acid toxicity contributes to lactic acidosis and citric acid cycle abnormalities in D-2-OHGA patients.
  • Further research is warranted to elucidate the precise molecular interactions between D-2-OHG acid and mitochondrial function.

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