NeurometPlus

Incidence

Rare. The disorder appear panethnic. This condition has been found in 26 patients. The first description of this disorder was in 1980 (for both types I and II). Consanguinity is present in type I. It is associated with mutations in the D2HGDH gene encoding D-2-hydroxyglutarate dehydrogenase (D-2-HGDH) which lead to impaired enzyme function.

Clinical Characteristics

Age of onset is generally within the first 6 years. Patients tend to have a different clinical picture although developmental delay is shared by most of them. Seizures were present in 30%, hypotonia in 60 %, developmental delay in 80 %, cardiomyopathy is not seen in type I. Extrapyramidal symptoms in 20 % and macrocephaly in 40 %. D-2-Hydroxyglutaric acid (D-2-HGA) concentration was elevated in urine, sometimes accompanied by increased 2-ketoglutaric acid excretion. Elevated concentration of D-2-HGA in plasma and CSF and total GABA in CSF were also reported. There seems to be a correlation between increasing D-2-HG concentrations and disease severity. CT Scan or MRI show enlarged ventricles and/or subarachnoid spaces in 40 % of cases. D-2-Hydroxyglutarate in urine was elevated in all patients. GABA in CSF was increased in 50 % of the times. There was no provocation test. There is no rational therapy for this disorder. There is no hypoglycemia, no metabolic acidosis nor lactic acidemia. Life expectancy remains undefined.

Precipitants

None

Provocation Tests

None. There was no provocation test.

Diagnostic Procedures

D-2-Hydroxyglutarate in urine was elevated in all patients. Although the clinical presentation often can suggest either D-2-HGA or L-2-HGA, chiral differentiation performed with GC-MS or liquid chromatography-tandem mass spectrometry (LC-MS/MS) is mandatory for the correct differential diagnosis