2-D,L- hydroxyglutaric aciduria. D,L-2-hydroxyglutaric aciduria. D,L-2-HGA.
Incidence
Currently 6 cases have been described. In 30% of cases, consanguinity is present. No mutations have been found. Prevalence: <1 / 1 000 000. Update 2017/ MGJM.
Clinical Characteristics
Most patients manifest a consistent clinical picture characterized by severe developmental delay, severe neonatal epileptic encephalopathy, often accompanied by respiratory insufficiency requiring artificial ventilation. This condition is biochemically characterized by moderately increased D-2-HG and L-2-HG in urine, mild increases of both metabolites in plasma, and a very slight elevation of D-2-HG in CSF and normal levels of L-2-HG in CSF. D-2-HG concentration exceeds L-2-HG in all fluids, while lactate and TCA cycle metabolites (succinate, fumarate and malate) were variably increased in urine, and 2-ketoglutarate was consistently increased in most patients. Most patients die in the first year of life, with occasional survival to 3 years of age. The brain MRI in all patients reveals enlarged ventricles, subependymal pseudo cysts and delayed gyration and myelination. In 1/6 of patients may occur hypotonia, developmental delay, seizures, cardiomyopathy and respiratory distress, with an MRI of brain suggestive of mitochondrial disease. The clinical picture on this 1/6 of patients suggest D-2-HGA type II but with different MRI findings, as well as elevated levels of L-2-HG, not present in D-2-HGA type II . No mutations have been found. Currently, treatment options are unavailable for combined D,L-2-HGA.
Precipitants
None
Provocation Tests
None.
Diagnostic Procedures
It is a clinical and laboratory diagnosis. This condition is biochemically characterized by moderately increased D-2-HG and L-2-HG in urine, mild increases of both metabolites in plasma, and a very slight elevation of D-2-HG in CSF and normal levels of L-2-HG in CSF.