Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenylketonuria, an autosomal recessively transmitted disorder of amino acid metabolism, is caused by a deficiency of hepatic phenylalanine hydroxylase converting phenylalanine to tyrosine. Thus, phenylalanine accumulates to plasma levels exceeding 1200 mumol/l. Untreated phenylketonuria is characterized by microcephaly, epilepsy, severe mental retardation and, in some cases, progressive supranuclear motor disturbances. These symptoms can largely be prevented by the early start of a phenylalanine-restricted diet. Neurological investigations of treated patients reveal only minor neurological signs, such as tremor or brisk deep tendon reflexes. Magnetic resonance imaging shows white matter abnormalities. However, in single patients, progressive neurological symptoms occurred. Thus, the long-term prognosis of treated phenylketonuria is still under discussion.
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PMID:Neurological aspects of adult phenylketonuria. 987 Jan 37

An elderly man with mental retardation who had never received dietary treatment for his phenylketonuria was placed on a phenylalanine-restricted diet. Social skills and walking gait improved and a new interest in the objects in his environment developed spontaneously. A 2-year analysis of diet, blood plasma phenylalanine levels and behavioural state indicated that small differences in phenylalanine intake impacted his well-being. Of significant note, leg tremor and spasm that precipitated severe self-injury were only reversible when plasma blood phenylalanine concentrations were titrated to near normal ranges and daily phenylalanine intake was strictly controlled. This case may offer a potential explanation for some of the late treatment failures that have been reported and suggest new avenues to explore in the late treatment of PKU.
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PMID:Benefits of normalizing plasma phenylalanine: impact on behaviour and health. A case report. 987 Feb 3

Phenylketonuria (PKU) is an autosomal recessive disorder resulting in neurological and intellectual disability when untreated. However, even in treated patients there may be residual neurological impairment such as tremor. It has been suggested that the hyperphenylalaninaemia in patients with PKU reduces complex I (NADH:ubiquinone reductase) activity of the mitochondrial respiratory chain (MRC) and/or biosynthesis of coenzyme Q(10) (CoQ(10)), which acts as an electron carrier in the MRC, leading to impaired energy metabolism in the brain of patients with PKU and hence the neurological pathology. The aim of this study was to elucidate the mechanism of phenylalanine (Phe) toxicity on the MRC. We compared mean plasma and blood-spot Phe and mononuclear CoQ(10) levels in 17 patients with PKU and a tremor compared to 22 patients without tremor. Human 1321N1 astrocytoma cells were exposed to hyperphenylalaninaemia by the addition of 300 or 900 micromol/L of Phe to the cell culture medium. Following 96 h of culture we measured complex I and citrate synthase activities and CoQ(10) level. Results showed no significant difference in Phe or CoQ(10) levels in patients with tremor compared to those without tremor. Further, hyperphenylalaninaemia did not cause a significant reduction in complex I activity or CoQ(10) biosynthesis, even when taking into account the mitochondrial enrichment of the cell samples by expressing complex I and CoQ(10) as a ratio to citrate synthase. In conclusion, the results of this study suggest that hyperphenylalaninaemia does not contribute to the pathophysiology of PKU by causing a decrease in MRC complex I activity and/or CoQ(10) biosynthesis.
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PMID:Assessment of mitochondrial respiratory chain function in hyperphenylalaninaemia. 1927 93

Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene or by defects in the tetrahydrobiopterin (BH4) synthesis pathway. Here, by positional cloning, we report that the 6-pyruvoyl-tetrahydropterin synthase (PTPS) gene, encoding a key enzyme of BH4 biosynthesis, is responsible for the alc (albino C) mutation that displays pale body color, head shaking, and eventually lethality after the first molting in silkworm. Compared to wild type, the alc mutant produced more substrates (phenylalanine (Phe) and tyrosine (Tyr)) and generated less DOPA and dopamine. Application of 2,4-diamino-6-hydroxypyrimidine (DAHP) to block BH4 synthesis in the wild type effectively produced the alc-like phenotype, while BH4 supplementation rescued the defective body color and lethal phenotype in both alc and DAHP-treated individuals. The detection of gene expressions and metabolic substances after drugs treatments in alc and normal individuals imply that silkworms and humans have a high similarity in the drugs metabolic features and the gene pathway related to BH4 and the dopamine biosynthesis. We propose that the alc mutant could be used as an animal model for drug evaluation for BH4-deficient PKU.
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PMID:Disruption of PTPS Gene Causing Pale Body Color and Lethal Phenotype in the Silkworm, Bombyx mori. 2959 27