Document Detail

D-2-Hydroxyglutaric aciduria in a patient with a severe clinical phenotype and unusual MRI findings.
MedLine Citation:
PMID:  11999977     Owner:  NLM     Status:  MEDLINE    
We report an infant with intermittent urinary excretion of D-2-hydroxyglutaric (D-2-OHG) acid who died at the age of 10 months from cardiogenic shock due to cardiomyopathy. High urinary concentrations of D-2-OHG and succinic acid, as well as increased levels of lactic acid were detected on three different occasions, whereas a normal urinary profile of organic acids was found on one occasion. The clinical findings of our patient consisted of generalized hypotonia, irritability, developmental delay, generalized tonic seizures, lethargy, cardiomyopathy, and respiratory distress. Cerebral MRI revealed bilateral lesions in the substantia nigra, the periaqueductal area, the medial part of the thalamus, the hypothalamus, the caudate nucleus, putamen and globus pallidus. This pattern is suggestive of a mitochondriopathy. However, respiratory chain enzyme activities were normal in fibroblasts. Exogenous supplementation of D-2-OHG acid strongly inhibited cytochrome-c oxidase activity in fibroblasts from the patient and from normal controls in vitro. The results suggest that our patient has an unusual form of D-2-hydroxyglutaric aciduria (D-2-OHGA), different from the patients published so far, and that the increase of lactic acid and some citric acid cycle intermediates encountered in some patients with D-2-OHGA may be due to a functional defect of the respiratory chain caused by D-2-OHG acid.
M Wajne; C R Vargas; C Funayama; A Fernandez; M L C Elias; S I Goodman; C Jakobs; M S van der Knaap
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of inherited metabolic disease     Volume:  25     ISSN:  0141-8955     ISO Abbreviation:  J. Inherit. Metab. Dis.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-05-09     Completed Date:  2002-11-19     Revised Date:  2007-03-21    
Medline Journal Info:
Nlm Unique ID:  7910918     Medline TA:  J Inherit Metab Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  28-34     Citation Subset:  IM    
Medical Genetics Service, Hospital de Clínicas de Porto Alegre, RS, Brazil.
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MeSH Terms
Brain / radiography*
Cardiomyopathies / radiography,  urine*
Cells, Cultured
Citrate (si)-Synthase / metabolism
Electron Transport Complex IV / metabolism
Fibroblasts / cytology,  enzymology
Glutarates / urine*
Magnetic Resonance Imaging
Shock, Cardiogenic / radiography,  urine*
Reg. No./Substance:
0/Glutarates; 2889-31-8/alpha-hydroxyglutarate; EC Transport Complex IV; EC (si)-Synthase

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