RESUMO
Hydroxysteroid (17beta) dehydrogenase 10 (HSD10) is a mitochondrial multifunctional enzyme encoded by the HSD17B10 gene. Missense mutations in this gene result in HSD10 deficiency, whereas a silent mutation results in mental retardation, X-linked, syndromic 10 (MRXS10). Here we report a novel missense mutation found in the HSD17B10 gene, namely c.194T>C transition (rs104886492), brought about by the loss of two forked methyl groups of valine 65 in the HSD10 active site. The affected boy, who possesses mutant HSD10 (p.V65A), has a neurological syndrome with metabolic derangements, choreoathetosis, refractory epilepsy and learning disability. He has no history of acute decompensation or metabolic acidosis whereas his urine organic acid profile, showing elevated levels of 2-methyl-3-hydroxybutyrate and tiglylglycine, is characteristic of HSD10 deficiency. His HSD10 activity was much lower than the normal control level, with normal ß-ketothiolase activity. The c.194T>C mutation in HSD17B10 can be identified by the restriction fragment polymorphism analysis, thereby facilitating the screening of this novel mutation in individuals with intellectual disability of unknown etiology and their family members much easier. The patient's mother is an asymptomatic carrier, and has a mixed ancestry (Hawaiian, Japanese and Chinese). This demonstrates that HSD10 deficiency patients are not confined to a particular ethnicity although previously reported cases were either Spanish or German descendants.
Assuntos
3-Hidroxiacil-CoA Desidrogenases/genética , Atetose/complicações , Coreia/complicações , Epilepsia/complicações , Epilepsia/genética , Deficiências da Aprendizagem/complicações , Mutação/genética , 3-Hidroxiacil-CoA Desidrogenases/química , Adulto , Sequência de Aminoácidos , Atetose/enzimologia , Atetose/genética , Atetose/urina , Sequência de Bases , Ácidos Carboxílicos/urina , Criança , Pré-Escolar , Coreia/enzimologia , Coreia/genética , Coreia/urina , Análise Mutacional de DNA , Eletroencefalografia , Transporte de Elétrons , Epilepsia/enzimologia , Epilepsia/urina , Feminino , Fibroblastos/enzimologia , Humanos , Recém-Nascido , Deficiências da Aprendizagem/enzimologia , Deficiências da Aprendizagem/genética , Deficiências da Aprendizagem/urina , Masculino , Redes e Vias Metabólicas , Mitocôndrias/enzimologia , Dados de Sequência Molecular , Polimorfismo de Fragmento de Restrição , GravidezAssuntos
Atetose , Coreia , Glutaratos/urina , Atetose/enzimologia , Atetose/urina , Coreia/enzimologia , Coreia/urina , Humanos , Lactente , Oxirredutases/deficiênciaRESUMO
The clinical symptoms in a 10-year-old girl with progressive dystonic cerebral palsy are described. The biochemical findings were dominated by large amounts of glutaric acid in the urine. The disorder is caused by impairment of the degradation of glutaryl-CoA. A survey is given of the clinical and biochemical symptoms, based on the five cases reported so far. It is concluded that patients with progressive dystonic palsy should be examined for disorders in the metabolism of organic acids.