Case reportl-2-hydroxyglutaric aciduria in two siblings
Introduction
Organic acidurias are a group of inherited metabolic disorders characterized by increased urinary excretion of organic acids. These disorders may present with episodes of severe metabolic decompensation or exclusively with severe neurologic disease. l-2-Hydroxyglutaric aciduria is a rare disorder belonging to the latter category.
l-2-Hydroxyglutaric aciduria was first reported in 1980 in a 5-year-old male who was investigated for global developmental delay [1]. A review of eight patients with characteristic pattern of a neurodegenerative disorder associated with the excretion of large amount of l-2-hydroxyglutaric acid was published in 1992 [2]. This study delineated the clinical, biochemical, and neuroimaging features of the disease as a clinical entity. Several other patients of various ethnic origins have been reported since 1992 [3], [4], [5], [6]. A more or less characteristic picture of the disease has emerged. Most of the patients had mental and motor retardation associated with ataxia. Pyramidal signs occurred frequently, and extrapyramidal signs appeared occasionally. Macrocephaly and seizures were often reported. All investigated patients demonstrated characteristic subcortical white matter abnormalities on magnetic resonance imaging [2], [7], [8], [9].
The diagnosis is established by detection of increased levels of l-2-hydroxyglutaric acid in urine [1], [2], [7]. Two clinical entities, l-2-hydroxyglutaric aciduria and d-2-hydroxyglutaric aciduria, are associated with increased 2-hydroxyglutaric acid excretion; therefore the absolute configuration of the metabolite should be determined [1], [10]. In this study we report on two siblings with l-2-hydroxyglutaric aciduria.
Section snippets
Patient 1
Patient 1 was a male who was born at term after an uneventful pregnancy, labor, and delivery. His birth weight was 3,000 g. He began to smile at 6 weeks, sit without support at 8 months, and walk at 20 months of age. He had a febrile seizure when he was 1 year of age. Full assessment was performed at 4.5 years of age. His weight was 16.5 kg (twenty-fifth percentile), length 101.9 cm (between the tenth and twenty-fifth percentiles), and fronto-occipital circumference 53.4 cm (between ninetieth
Discussion
The increased urinary l-2-hydroxyglutaric acid excretion confirms the diagnosis of l-2-hydroxyglutaric aciduria [2]. The clinical picture of the two patients fits a chronic, slowly progressive neurodegenerative disorder with insidious onset after infancy. No significant abnormalities were noted in the first year of life; developmental delay appeared later. Mental regression and seizures were found in both children. Clinically cerebellar dysfunction was the main motor handicap in Patient 1,
Acknowledgements
We thank Professor Peter G. Barth for his useful comments on the magnetic resonance imaging study and Ashok Prasad for taking the photographs for this report.
References (15)
- et al.
L-2-Hydroxyglutaric aciduriaAn inborn error of metabolism?
J Inher Metab Dis
(1980) - et al.
L-2-Hydroxyglutaric acidemiaA novel inherited neurometabolic disease
Ann Neurol
(1992) - et al.
Clinical and magnetic resonance imaging features of L-2-hydroxyglutaric acidemiaReport of three cases in comparison with Canavan disease
J Child Neurol
(1996) - et al.
L-2-Hydroxyglutaric aciduriaClinical heterogeneity versus biochemical homogeneity in a sibship
Neuropediatrics
(1997) - et al.
L-2-Hydroxyglutaric aciduriaMRI in seven cases
Neuroradiology
(1998) - et al.
L-2-Hydroxyglutaric aciduriaTwo Japanese adult cases in one family
J Neurol
(1999) - et al.
L-2-Hydroxyglutaric acidemiaClinical and biochemical findings in 12 patients and preliminary report on L-2-hydroxyacid dehydrogenase
J Inher Metab Dis
(1993)
Cited by (20)
Eyelid myoclonia with absence seizures in a child with L-2 hydroxyglutaric aciduria: Findings of magnetic resonance imaging
2012, Pediatric NeurologyCitation Excerpt :l-2 hydroxyglutaric aciduria is a rare metabolic disorder characterized by a progressive neurologic syndrome of cerebellar and pyramidal signs, mental deterioration, tremor, and extrapyramidal signs during the first years of age. Seizures, epilepsy, and macrocephaly may constitute additional findings [1]. Metabolic disorders rarely present with seizures in isolation [2].
Postural tremor in L-2-hydroxyglutaric aciduria is associated with cerebellar atrophy
2022, Neurological SciencesMovement Disorders in Childhood, Third Edition
2022, Movement Disorders in Childhood, Third EditionMovement Disorders in Childhood
2015, Movement Disorders in ChildhoodCerebral neoplasms in L-2 hydroxyglutaric aciduria: 3 New cases and meta-analysis of literature data
2012, American Journal of Neuroradiology
- 1
Peter Vreken is deceased.