Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02079 (lysine)
 58,762 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A mentally retarded, 10-year-old female with obesity, hypotonia, clumsiness and mild ocular abnormalities excreted in her urine large amounts of alpha-aminoadipic acid. Amino acid analyser studies and gas-liquid chromatography--mass spectrometry (GC--MS) confirmed the presence of alpha-aminoadipic acid in both urine and plasma but, in contrast to most other patients with this disorder, failed to demonstrate significant levels of alpha-ketoadipic acid in urine. Other known causes of alpha-aminoadipic aciduria were eliminated by showing that levels of lysine, saccharopine and pipecolic acid in plasma and urine were normal and that the activity of glutaryl-CoA dehydrogenase was also normal. Loading with L-lysine and L-tryptophan both increased the concentration of alpha-aminoadipic acid in blood and urine compatible with the primary deficiency of alpha-ketoadipate dehydrogenase, in spite of the absence of alpha-ketoadipic aciduria. Dietary restriction of lysine and administration of vitamins B1 and B6 were unsuccessful in correcting the biochemical abnormality.
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PMID:Biochemical and clinical studies of a new case of alpha-aminoadipic aciduria. 11 47

We report cystinuria and symptoms of cerebellar atrophy in a 45-year-old man. His parents were first cousins, and many members of his family had stones of urinary tract or gait impairment. Neurological examination disclosed cerebellar signs resembling those of spinocerebellar degeneration. Urinalysis disclosed high cystine, lysine, ornitine and arginine output. Cystine was 1153.8 micro mol/day (normal range, 22-170); lysine, 3443.9 (normal range, 44-1000); ornitine, 283.8 (normal range, 7-40); and arginine, 154.0 (normal range, 9-50). Neurological complications reported to be associated with cystinuria include mental retardation, muscular dystrophy, hypotonia and dwarfism, mongolism, paroxysmal dyskinesia, myopathy, migraine, spastic paraplegia, multiple sclerosis, subacute combined degeneration and cranial polyneuropathy. Cerebellar signs have been reported in only two cases, and to our knowledge, this is the first case of cystinuria with cerebellar atrophy ever reported. Some common metabolic errors may have caused both disorders, although they also may have developed independently.
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PMID:[Cystinuria with symptoms of cerebellar atrophy--a case report]. 189 74

The plasma pipecolic acid concentration in two newborn infants with Zellweger syndrome at ages 4 and 10 days were 7.8 and 7.7 microM. Reported concentrations from this laboratory for normal newborn infants averaged 12 microM +/- 5.6 (SD). Both patients had the facies and severe hypotonia characteristic of the disease. Autopsy examination at age 6 days in one of these patients revealed the developmental microscopic abnormalities in brain, liver, and kidney that are associated with Zellweger syndrome. In three additional patients ages 3 1/2 weeks, 2 months, and 2 months, the pipecolic acid concentrations were 15, 17, and 25 microM. The concentrations increased to distinctly pathological levels on subsequent assays at a later age. It is concluded that the hyperpipecolatemia in Zellweger syndrome occurs postpartum and that the plasma concentrations may not be diagnostic early in life. The major manifestations of the disease, already evident at birth, cannot be attributed to pipecolatemia. Currently available data do not exclude the possibility of pipecolic acid accumulation in the brain where it has been reported to be a major metabolite of lysine. Hyperpipecolatemia of considerable degree is also consistently found in familial hyperlysinemia where it appears to be benign.
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PMID:The significance of hyperpipecolatemia in Zellweger syndrome. 308 61

The case of a mentally retarded girl with a number of dysmorphic features, Raynaud's phenomenon, hypotonia and petit mal seizures is presented. Laboratory investigations showed alpha-aminoadipic aciduria and a high level of fetal haemoglobin. Oral L-lysine loading resulted in a marked increase of alpha-aminoadipic acid in blood and urine. After 3 months of pyridoxine medication the increase of alpha-aminoadipic acid in blood and urine during the oral L-lysine loading test was less than in the test before treatment. A normal degradation rate of DL-alpha-amino [1-14C] adipic acid in fibroblasts of the patient, as measured by 14CO2 production, did not indicate a primary enzyme defect in the alpha-aminoadipic acid transamination or decarboxylation steps. The persistent HbF could be the result of stress on the erythropoiesis by a secondary induced defect in an early stage of haemoglobin synthesis in which alpha-amino-beta-ketoadipic acid, a structural analogue of alpha-amino-adipic acid, is an intermediate.
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PMID:alpha-Aminoadipic aciduria and persistence of fetal haemoglobin in an oligophrenic child. 616 32

Pipecolic acid (PA) is an intermediate of lysine metabolism in the mammalian brain. Recent findings suggest a functional connection of PA as neuromodulator in GABAergic transmission. Since many drugs are postulated to produce their effects by interaction with the central GABA system, the influence of PA on the anticonvulsant activity of phenobarbital was examined. Pretreatment of mice with 50 mg . kg-1 of PA potentiated the suppressing effects of the barbiturate on electrically and chemically induced convulsions. However, there was no potentiation of the behavioral effects and hypothermia induced by phenobarbital. PA itself had no or only little effect on the convulsions, motor function and rectal temperature when given in i.p. doses up to 500 mg . kg-1. Intraventricular administration of 500 microgram of PA also did not suppress either type of convulsion, although it produced ptosis, hypotonia, sedation and hypothermia. The results are discussed in relation to GABA system.
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PMID:Potentiation of phenobarbital-induced anticonvulsant activity by pipecolic acid. 628 9

Bejar et al. described increased concentrations of valine, leucine and isoleucine in the plasma of 2 patients with cerebral gigantism (Sotos-syndrome). We have recently investigated a group of 14 children with Sotos-syndrome. The data of the plasma amino-acid determinations were compared with those of aged-matched healthy controls, 9 children with benign muscular hypotonia, 10 children with Down's syndrome and finally with those of 13 children with familial tall stature. The mean concentration of serine, glutamic acid, valine, isoleucine, leucine and phenylalanine was lower in the patients with Sotos-syndrome when compared to the healthy control group. However, all patients with benign muscular hypotonia and Down's syndrome showed increased concentrations of proline, glycine, alanine, ornithine and lysine in the plasma whereas the mean values of the children with familial tall stature differed only slightly from those of the controls. The levels of the plasma-aminoacids in patients with Sotos-syndrome were only slightly different from those in patients with muscular hypotonia, but generally lower than in tall children. We conclude that the determination of plasma-aminoacids is of no value in the diagnosis of Sotos-syndrome.
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PMID:[Amino acids in plasma of patients with cerebral gigantism (Sotos syndrome) (author's transl)]. 645 99

A boy, aged 7 months, of consanguineous parents presented with an acute onset of vomiting, fever, nonketotic hypoglycemia and acidosis and died from cardiac arrest after ventricular fibrillation. He had hepatomegaly and echocardiographically a non-obstructive cardiomyopathy. Autopsy was not allowed. After birth the child had suffered from a severe respiratory distress syndrome, transient metabolic acidosis and had a sweaty feet odour. Later on, development was retarded with a severe muscular hypotonia. Post mortem, numerous unusual organic acids were found in high concentrations in urine, e.g. dicarbonic acids, 2-hydroxyisobutyric, isovaleric, 3-hydroxyisovaleric acid, N-acyl glycines, isovalerylglutamic acid and sarcosine. This pattern indicated deficiencies of several acyl-Co A dehydrogenases in the metabolism of leucine, isoleucine, valine, lysine, short-chain fatty acids and sarcosine. This could be confirmed using cultured skin fibroblasts which were shown to degrade the corresponding labeled substrates insufficiently to 14CO2. It is assumed that the functional multiple acyl-Co A dehydrogenation deficiency is caused by a deficiency of a common link in the electron transfer system of these dehydrogenases which is inherited autosomal recessively in this family. Among the 12 patients reported, 7 died within the first 5 days of age.
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PMID:Multiple acyl-Co A dehydrogenation deficiency (MADD) in a boy with nonketotic hypoglycemia, hepatomegaly, muscle hypotonia and cardiomyopathy. Detection of N-isovalerylglutamic acid and its monoamide. 686 97

Lysinuric protein intolerance (LPI) is an autosomal recessive disease caused by defective transport of the cationic amino acids lysine, arginine, and ornithine at the cell membrane. About 80 patients with LPI have been described worldwide, almost half of them in Finland. The symptoms appear in early childhood as a failure to thrive, growth retardation, muscular hypotonia, and episodes of stupor after protein-rich meals. Twenty-nine Finnish patients (current median age 24.8 years, range 3.7-47.9 years) over a mean follow-up time of 18.1 years (range 1.2-27.2 years) had 57 fractures after minor trauma, mostly in childhood. Their 440 skeletal radiographs showed severe osteoporosis (13/29), controversially abnormal thickening of cortex of the metacarpals (7/29), or thin cortices of the long bones (5/29), endplate impression of vertebrae (8/29), rickets-like metaphyses (2/29), or early destruction of cartilage (3/29). Skeletal maturation was delayed by 1-5 years in 23 of 24 patients. There was no correlation between fracture incidence, radiological bone structure, and delayed skeletal maturation.
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PMID:Skeletal manifestations of lysinuric protein intolerance. A follow-up study of 29 patients. 843 Mar 40

Infants with macrocephaly, young children with acute disease resembling encephalitis, and children with truncal hypotonia, ataxia, or dystonia may be affected by glutaric aciduria type I (GA 1, glutaryl-CoA-dehydrogenase deficiency), a not-so-rare autosomal recessive neurometabolic disease. Well-known features of GA1 are fronto-temporal brain atrophy with macrocephaly and acute encephalopathic episodes with striatal necrosis followed by dystonia, but some patients develop motor disease without overt crises and other biochemically affected individuals remain asymptomatic. Biochemical and molecular characterization is available and allows post- and prenatal diagnosis. The pathogenesis of fronto-temporal atrophy, macrocephaly, and basal ganglia necrosis is still not understood, and there is no close correlation between biochemical parameters and clinical outcome. There is, however, evidence suggesting that carnitine supplementation and anticatabolic treatment of intercurrent illness may arrest or prevent neurological deterioration, while the role of limitation of dietary lysine and tryptophane is not yet clear. Although pathogenetic aspects are poorly understood, the natural course of glutaric aciduria type 1 can be changed by early diagnosis and treatment. Coordinated research is needed to understand the pathogenesis of brain toxicity, to define the role of dietary therapy, and to explore the possibility of neonatal screening.
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PMID:Glutaric aciduria type 1 (glutaryl-CoA-dehydrogenase deficiency): advances and unanswered questions. Report from an international meeting. 939 91

4-Aminobutyrate aminotransferase (GABA-transaminase, GABA-T, EC 2.6.1.19) deficiency (McKusick 137150), an inborn error of GABA degradation, has until now been documented in only a single Flemish child. Compared to the other defects of GABA degradation, succinic semialdehyde dehydrogenase (SSADH, EC 1.2.1.24) deficiency with > 150 patients (McKusick 271980) and pyridoxine-dependent seizures with > 100 patients ('putative' glutamic acid decarboxylase (GAD, EC 4.1.1.15) deficiency; McKusick 266100), GABA-T deficiency is very rare. We present a summary of the clinical, biochemical, enzymatic and molecular findings on the index proband, and a recently identified second patient, with GABA-T deficiency. The phenotype in both included psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures and electroencephalographic abnormalities. In an effort to elucidate the molecular basis of GABA-T deficiency, we isolated and characterized a 1.5 kb cDNA encoding human GABA-T, in addition to a 41 kb genomic clone which encompassed the GABA-T coding region. Standard methods of cloning and sequencing revealed an A-to-G transition at nucleotide 754 of the coding region in lymphoblast cDNAs derived from the index proband. This mutation resulted in substitution of an invariant arginine at amino acid 220 by lysine. Expression of the mutant in E. coli, followed by isolation and enzymatic characterization of the recombinant protein, revealed an enzyme whose Vmax was reduced to 25% of wild-type activity. The patient and father were heterozygous for this allele; the second allele in the patient remains unidentified. Genomic Southern analysis revealed that the second proband most likely harbours a deletion in the 3' region of the GABA-T gene.
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PMID:4-Aminobutyrate aminotransferase (GABA-transaminase) deficiency. 1040 78


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