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Metabolic disease resulting in abnormal MRI findings and psychomotor retardation, hypotonia, and nonneurologic signs.

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Incidence is unknown, but approximately 30 cases have been reported. Inheritance is autosomal recessive.

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The enzymatic defect causing this progressive neurometabolic disorder has not been found. d-2-Hydroxyglutaric acid is a stereoisomer of l-2-hydroxyglutaric acid and an intermediate in glutamate, 5-aminolevulinic acid, and gamma-aminobutyric acid (GABA) metabolism. Elevated levels of GABA were found in the cerebrospinal fluid of some patients with d-2-hydroxyglutaric aciduria. A mild and a severe phenotype have been reported, with a more variable clinical picture and less consistency seen on MRI findings of the mild phenotype. Regardless of the phenotype, progressive psychomotor degeneration with macrocephaly, epilepsy (hypsarrhythmia), hypotonia, cerebral and/or cerebellar atrophy with cerebellar ataxia, and mental and motor developmental delay can be found. The most consistent MRI findings are enlargement of the lateral ventricles, subependymal cysts, and signs of delayed cerebral maturation. Nonneurologic manifestations include prenatal and postnatal growth retardation, cardiomyopathy, facial anomalies, and episodic vomiting. Inspiratory stridor and apnea were the reasons for tracheotomy in one patient at age 4 months.

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Facial anomalies, which may affect the airway management, have been reported in a minority of cases. Anomalies include macrocephaly and microcephaly, micrognathia, prognathia, and midface hypoplasia. Hypertrophic cardiomyopathy and aortic insufficiency have been reported and warrant preoperative investigation. Check serum electrolytes and volemia in case of recurrent vomiting, and perform a rapid-sequence induction if general anesthesia is required.

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L-2-Hydroxyglutaric Aciduria: Inborn error of metabolism manifesting as progressive neurodegenerative disorder with psychomotor retardation.

Amiel J, de Lonlay P, Francannet C, et al: Facial anomalies in D-2-hydroxyglutaric aciduria. Am J Med Genet 86:124, 1999.  [PubMed: 10449646]
Nyhan WL, Shelton D, Jakobs C, et al: D-2-hydroxyglutaric aciduria. J Child Neurol 10:137, 1995.  [PubMed: 7782605]
Van der Knaap MS, Jakobs C, Hoffmann GF, et al: D-2-hydroxyglutaric aciduria: Further clinical delineation. J Inherit Metab Dis 22:404, 1999.

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