L2-hydroxyglutaric aciduria in a 5-year-old child: a case report

Case presentation: EMS, 5 years old, 1st child of a non-consanguineous couple, with no relevant antecedents, have started a neuropsychomotor development regression at 2 years old. The parents noticed a slower speech, in addition to a bad concentration. At the first appointment at a tertiary pediatric neurology service in the city of São Paulo, the patient had a lowered cognitive level for his age, in addition to bradylalia and dysarthria. He had an unsupported gait, on tiptoe, with a slightly enlarged base. The eye examination, inborn error of metabolism trial, cerebrospinal fluid and general serum exams were normal. Cranial magnetic resonance imaging showed bilateral and symmetrical involvement of the basal ganglia and dentate nuclei, associated with changes in the supratentorial white matter. A genetic panel was collected, confirming L2-glutaric aciduria, with 2 pathogenic variants of L2HGDH.

Discussion: L-2-hydroxyglutaric aciduria is a rare, autosomal recessive disease caused by mutations in the L2HGDH gene (14q22.1) that encodes mitochondrial 2-hydroxyglutarate dehydrogenase. It consists of an organic cerebral aciduria of insidious onset, with slow progression, generating neurological symptoms. L-2-hydroxyglutaric acid accumulates in urine, blood, and CSF. Cranial MRI shows characteristic abnormalities: symmetrical lesions in the white matter and corpus callosum, in addition to changes in the basal ganglia and cerebellum. Clinical manifestations consist of mild to moderate NPMD delay, cerebellar ataxia, epilepsy, and spasticity. Macrocephaly and extrapyramidal symptoms are present in 50% of cases.

Final comments: The presentation of this case report is justified due to the rarity of this genetic condition, with ~200 cases reported so far. Although the clinical picture is nonspecific, imaging changes may suggest the diagnosis, which must be confirmed by molecular test.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023