Inborn error of metabolism manifesting as progressive
neurodegenerative disorder with psychomotor retardation.
The incidence is unknown, but
approximately 20 cases have been reported. Transmission is autosomal
The enzymatic defect causing this progressive
neurometabolic disorders is yet to be found. l-2-Hydroxyglutaric acid
is a stereoisomer of d-2-hydroxyglutaric acid. Elevated levels of l-2-hydroxyglutaric acid are found in the urine, cerebrospinal fluid (CSF),
and, to a lesser degree, in the serum. Plasma and CSF levels of lysine are
elevated in some of these patients. In most patients, the initial symptoms
are a delay of speech, unsupported walk and febrile seizures within the first
2 years of life. Over the following years, mental retardation associated to
cerebellar ataxia with or without dystonia, pyramidal signs, and seizures
develop. However, onset can be as early as neonatal age or as late as
adolescent age. The oldest patient reported with this disorder was 57 years
old. MRI scans reveal a consistent pattern with symmetrical subcortical
leukoencephalopathy and cerebellar atrophy (vermis more than hemispheres).
Furthermore, pathologic changes can—although inconsistently—be detected
in the dentate nuclei, putamina, and globus pallidus.
Macrocephaly is a common feature, but no
other facial anomalies have been reported, so airway management should not
be affected. Keep in mind that these patients may be taking antiseizure
medication, and potential interaction with other drugs and altered hepatic
metabolism can occur.
Canavan Syndrome: Progressive leukodystrophy caused by spongy
degeneration of the central nervous system. It is uniformly fatal.
d-2-Hydroxyglutaric Aciduria: Metabolic disease resulting in
abnormal MRI findings and psychomotor retardation, hypotonia, and
non neurologic signs.
Barth PG, Hoffmann GF, Jaeken J, et al: l
acidemia: A novel inherited neurometabolic disease. Ann Neurol
Fujitake J, Ishikawa Y, Fujii H, et al: l
Two Japanese adult cases in one family. J Neurol
Topcu M, Erdem G, Saatci I, et al: Clinical and magnetic resonance imaging
features of l
-2-hydroxyglutaric acidemia: Report of three cases in
comparison with Canavan disease. J Child Neurol