L-2-hydroxyglutaric aciduria: clinical, neuroimaging, and neuropathological findings.
BACKGROUND
l-2-Hydroxyglutaric aciduria is a rare, infantile-onset, autosomal recessive organic aciduria affecting exclusively the central nervous system. To our knowledge, only 1 complete report of the neuropathological findings in an adult has been published.


OBJECTIVE
To present the clinical, neuroimaging, and neuropathological findings of l-2-hydroxyglutaric aciduria.


METHODS
Case report.


METHODS
Complexo Hospitalario de Pontevedra, Pontevedra, Spain.


METHODS
A 15-year-old boy who had early infantile-onset progressive psychomotor regression, mild choreodystonia affecting the distal part of the upper limbs, pyramidal signs, and epilepsy.


RESULTS
The diagnosis of l-2-hydroxyglutaric aciduria was confirmed by the finding of highly elevated levels of l-2-hydroxyglutaric acid in the serum, urine, and cerebrospinal fluid. The neuroimaging findings showed striking confluent subcortical white matter lesions and minimal basal ganglia (pallidum, thalamic, and putaminal) abnormalities. The patient died of a spontaneous mesenteric thrombosis. The postmortem neuropathological findings showed spongiosis and cystic cavitations in subcortical white matter, with minimal abnormalities of the basal ganglia. The dentate nucleus, a structure usually affected in neuroimaging studies, showed minimal neuronal loss but was surrounded by important spongiosis and microvacuolation with astrocytic proliferation.


CONCLUSIONS
This case reaffirms that l-2-hydroxyglutaric aciduria is a spongiform type of leukoencephalopathy with cystic cavitations predominating in the subcortical areas. Although the neuroimaging findings are highly characteristic of the disease, in this patient cerebellar abnormalities were minimal and dentate signal abnormalities were not present.
Seijo-Martínez
Manuel
M
Department of Neurology, Complexo Hospitalario de Pontevedra, Spain. mseijom@meditex.es
Navarro
Carmen
C
Castro del Río
Maria
M
Vila
Oscar
O
Puig
Miguel
M
Ribes
Antonia
A
Butron
Mercedes
M
D000293:Adolescent; D001284:Atrophy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D020739:Brain Diseases, Metabolic, Inborn / Q000097:blood* / Q000473:pathology* / Q000652:urine; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D017809:Fatal Outcome; D005492:Folic Acid / Q000627:therapeutic use; D005808:Genes, Recessive / Q000235:genetics; D005977:Glutarates / Q000097:blood* / Q000134:cerebrospinal fluid / Q000652:urine*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008641:Mesenteric Vascular Occlusion / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008642:Mesenteric Veins / Q000473:pathology / Q000503:physiopathology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D013030:Spain
D005977:Glutarates; C019417:alpha-hydroxyglutarate; D005492:Folic Acid