Case reportl-2-Hydroxyglutaric aciduria presenting with severe autistic features☆
Introduction
l-2-Hydroxyglutaric aciduria (l-2-HGA) is a rare autosomal recessive metabolic disorder, affecting exclusively the central nervous system. It is characterized by a defect in the metabolism of l-2-hydroxyglutaric acid and, consequently, increased levels of the acid in urine, cerebrospinal fluid and plasma [1]. The disorder has been mapped to chromosome 14q22.1 and, more specifically, to the gene encoding l-2-hydroxyglutarate dehydogenase (L2HGDH) [2]. l-2-HGA was first described in 1980 and since then about 75 cases have been reported worldwide [1]. Nevertheless, a distinct clinical and neuroradiological picture has emerged, as the disease has a relatively consistent pattern of presentation.
Clinically, l-2-HGA is characterized by mild psychomotor delay in the first years of life, followed by progressive cerebellar ataxia, dysarthria and moderate-to-severe mental deterioration, whereas macrocephaly, pyramidal and extrapyramidal signs, seizures and dystonia are present in the majority of patients. As far as behavioral and communication issues are concerned, several patients demonstrate language deficits and hyperactivity, whereas others are described during childhood as “talkative, almost in an uninhibited manner”. Briefly, MRI findings, which seem to be consistently unique of l-2-HGA, include subcortical white matter loss, cerebellar atrophy and bilateral signal changes in dentate nuclei and putamens [1].
In this brief report, the clinical and genetic features of a 3-year-old boy with l-2-HGA and severe autism are described.
Section snippets
Case report
The patient was referred to the neurodevelopmental department at the age of 4 months, because of macrocephaly, already noted in intrauterine life. He is the second child of healthy, non-consanguineous parents of caucasian origin. An older sister is entirely normal according to the parents and public health book information. Pregnancy was uneventful; however, he was delivered by caesarean section due to cephalopelvic disproportion (head circumference at birth 38.5 cm, > +2 SD). On the second day
Discussion
l-2-HGA is a rare neurometabolic disorder with a consistent clinical and radiological presentation. Psychomotor delay, ataxia and macrocephaly, in addition to the typical neuroradiological findings of subcortical leukoencephalopathy, are highly suggestive of the diagnosis. Macrocephaly is present in almost 50% of patients with l-2-HGA and it can be the first manifestation of the disease [1], [2], sometimes noted already in intrauterine ultrasound scans, as in this boy. Therefore, the presence
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Cited by (21)
Structure and biochemical characterization of L-2-hydroxyglutarate dehydrogenase and its role in the pathogenesis of L-2-hydroxyglutaric aciduria
2024, Journal of Biological ChemistryKetogenic diet exposure during the juvenile period increases social behaviors and forebrain neural activation in adult Engrailed 2 null mice
2016, Physiology and BehaviorCitation Excerpt :Emerging evidence suggests that KD or modified KD could have clinical utility for other neurological and developmental disorders [11–15]. Several developmental disorders, such as autism spectrum disorder (ASD), could realize benefits from KD because there are few effective treatment options and some behaviors are thought to involve neurometabolic impairments [16,17]. Indeed, there is limited clinical evidence to suggest mild to moderate improvements in autism-related behaviors in ASD subjects undergoing a 6-month intermittent KD intervention [18].
Identification of organic acids as potential biomarkers in the urine of autistic children using gas chromatography/mass spectrometry
2014, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesCitation Excerpt :Moreover, the results may also show elevated values as a result of ingestion of food [64]. The increase in α-hydroxyglutaric acid (2-hydroxyglutaric acid) in the urine of autistic children was described by Zafeiriou and co-worker [73]. The highest values of 3-hydroxyglutaric acid for a child with autism were found by Shaw et al. [61].
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No financial assistance was received in support of the study.