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)

We previously verified the effectiveness of tetrahydrobiopterin (BH4) on the ataxia in Machado-Joseph disease (MJD; SCA3 [spinocerebellar ataxia type 3]) as one of the most common types of dominantly inherited spinocerebellar ataxias. We hypothesized as to the pharmacological mechanism of BH4 that on the basis of 'cerebellar long-term depression' theory, BH4 may exert its actions at the levels of soluble guanylate cyclase in the Purkinje cells and of nitric oxide synthase in the granule cells. If cerebellar long-term depression is the case as the theoretical basis of BH4, it will open a new page of therapeutic strategy for spinocerebellar ataxias.
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PMID:Effects of tetrahydrobiopterin on ataxia in Machado-Joseph disease may be based upon the theory of 'cerebellar long-term depression'. 1146 Nov 69

DHPR deficiency is a rare autosomal recessively inherited metabolic disorder of tetrahydrobiopterin (BH4) regeneration. Clinical symptoms may comprise microcephaly, developmental delay, ataxia and seizures. BH4 is the cofactor for the enzyme phenylalanine (Phe)hydroxylase (PAH), and for tryptophan and tyrosine hydroxylases, both of which are essential for serotonin and dopamine biosynthesis. We present four patients in two families who are being treated at the National Centre for Inherited Metabolic Disorders (NCIMD). All are members of the Irish Traveller population. We have identified a homozygous mutation, c.353C>T, in the DHPR (QDPR) gene which, to the best of our knowledge, has not been previously described. The mainstay of treatment is a life-long Phe-restricted diet together with supplementation of L-dopa and 5-hydroxy tryptophan (5-HT) and folinic acid. In Ireland, there is neurological comorbidity in our adult DHPR patients, although the overall outcome is satisfactory and one affected female has three healthy children.
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PMID:'Malignant Phenylketonuria' (PKU) Due to Dihydropteridine Reductase (DHPR) Deficiency. 2681 92

Dopa-responsive dystonia due to sepiapterin reductase deficiency (OMIM#612716) is caused by recessive mutations in the gene encoding sepiapterin reductase (SPR), which plays an important role in the biosynthesis of tetrahydrobiopterin (BH4). One Jordanian patient to first cousin parents is reported in this study. The parents of the proband have recognized the symptoms of their daughter at six months old with motor developmental delay. The symptoms were progressed after-then to include speech delay, seizure, ataxia, oculomotor apraxia, dysarthia and choreoathetosis. Despite of these symptoms, the clinicians in Jordan were unable to diagnose the case. In August 2018, the proband (8 years old) was presented to the department of biotechnology and genetic engineering at Philadelphia University in Jordan for the purposes of performing whole exome sequencing (WES). Analysis of WES data has revealed novel homozygous frameshift variant in the gene SPR (NM_003124.4:c.40delG,p.Ala15Profs*100). The variant is heterozygous in the parents and in the healthy male siblings. Therefore, the studied case was diagnosed with sepiapterin reductase deficiency. Because this disease is likely to be treated recommendations were given to the family immediately to start treatments trials. The case in this study illustrates the difficulties of diagnosing sepiapterin reductase deficiency based on clinical symptoms only and thus renders the possibilities of early management. Also, this study reinforces the importance of running WES to undiagnosed neurodevelopmental cases.
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PMID:Genetic study in a family with dopa-responsive dystonia revealed a novel mutation in sepiapterin reductase gene. 3177 25