Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Loss-of-function and hypomorphic ECHS1 variants are associated with mitochondrial short-chain enoyl-CoA hydratase deficiency, an inborn error of valine metabolism. We report an 8-year-old boy with developmental delay, ataxia, hemiplegia, and hearing loss with abnormalities in the basal ganglia. Biochemical studies were essentially normal except for a persistent mildly elevated CSF alanine. This patient demonstrates an intermediate phenotype between a Leigh-like, early-onset presentation and paroxysmal exercise-induced dyskinesia. Two novel ECHS1 variants (c.79T>G; p.Phe27Val and c.789_790del; p.Phe263fs) were identified via exome sequencing in the proband, and pathogenicity was confirmed by enzyme assay performed on patient fibroblasts. Neither of the ECHS1 variants detected in the child were present in the mother. However, due to nearby polymorphisms, it was possible to determine that p.Phe263fs occurred de novo on the maternal chromosome and that p.Phe27Val likely derived from the paternal chromosome. Nearby polymorphisms can help set phase of variants when only a single parent is available for testing or when an identified variant occurs de novo.
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PMID:Extrapolation of Variant Phase in Mitochondrial Short-Chain Enoyl-CoA Hydratase (ECHS1) Deficiency. 2992 89

Mitochondrial disorders (MDs) are inherited multi-organ diseases with variable phenotypes. Inclusion body myositis (IBM), a sporadic inflammatory muscle disease, also shows mitochondrial dysfunction. We investigated whether primary and secondary MDs modify metabolism to reveal pathogenic pathways and biomarkers. We investigated metabolomes of 25 mitochondrial myopathy or ataxias patients, 16 unaffected carriers, six IBM and 15 non-mitochondrial neuromuscular disease (NMD) patients and 30 matched controls. MD and IBM metabolomes clustered separately from controls and NMDs. MDs and IBM showed transsulfuration pathway changes; creatine and niacinamide depletion marked NMDs, IBM and infantile-onset spinocerebellar ataxia (IOSCA). Low blood and muscle arginine was specific for patients with m.3243A>G mutation. A four-metabolite blood multi-biomarker (sorbitol, alanine, myoinositol, cystathionine) distinguished primary MDs from others (76% sensitivity, 95% specificity). Our omics approach identified pathways currently used to treat NMDs and mitochondrial stroke-like episodes and proposes nicotinamide riboside in MDs and IBM, and creatine in IOSCA and IBM as novel treatment targets. The disease-specific metabolic fingerprints are valuable "multi-biomarkers" for diagnosis and promising tools for follow-up of disease progression and treatment effect.
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PMID:Metabolomes of mitochondrial diseases and inclusion body myositis patients: treatment targets and biomarkers. 3037 90

In some inherited metabolic diseases, in particular in urea cycle disorders, which are usually diagnosed in neonatal period or in childhood, vomiting is often the first symptom. We report a case of late revelation of urea cycle disorder in a 13 years old female patient hospitalized for convulsions and failure to thrive. The patient underwent an interview revealing chronic vomiting associated with behavioral disorders, ideomotor slowdown and headaches. Clinical examination showed ataxia. Lumbar puncture and head CT scan were normal. The patient had substantially elevated blood ammonia level at 75 micromoles/L (11-50). Chromatography of amino acids in the blood showed increased glutamine and alanine. Chromatography of amino acids in the urine showed increased basic amino acids evoking a deficit of the urea cycle due to deficit of the enzyme argininosuccinate lyase. The patient was treated as an emergency, exclusively with glycolipid-diet and sodium benzoate, allowing improvement of patient's clinical condition and weight resumption. The seizures were controlled by phenobarbital. Family interview revealed that patient's sister, aged 20 years, had a 3-year history of seizures treated with phenobarbital. She underwent metabolic assessment in our department, which showed the same urea cycle abnormality as hes sister. Urea cycle deficiency should be suspected in patients of any age with encephalopathy associated with epilepsy, vomiting, weight stagnation and hyperammonemia. The diagnosis is very often made during severe neurodigestive attack involving vomiting, attack and/or seizures.
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PMID:[Vomiting associated with weight stagnation and convulsions: urea cycle disorder should be suspected]. 3103 64


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