1/171. Molecular characterization of 6-pyruvoyl-tetrahydropterin synthase deficiency in Japanese patients.We identified three mutations in four Japanese patients with central type 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. One missense mutation was a C-to-T transition, resulting in the substitution of Pro by Ser at codon 87 (P87S) in exon 5. Another missense mutation was a G-to-A transition, resulting in the substitution of Asp by Asn at codon 96 (D96N) in exon 5. A splicing mutation was found by skipping of exon 4 on PTPS mRNA analysis, and a G-to-A transition at the third base of codon 81 (E81E) and at the terminal base in exon 4 were detected on genomic PTPS dna analysis. The E81E mutation affected the splice donor site of exon 4 and caused the splicing error. In COS cell expression analysis, the P87S and D96N mutant constructs revealed, respectively, 52% and 10% of wild-type activity. patients with P87S/P87S (52%/52% in-vitro PTPS activity) exhibited 0.11 and 0 microU/g hemoglobin [Hb] in erythrocyte PTPS activity (wild-type control: 11-29 microU/gHb) erythrocyte PTPS activity, and the patient with P87S/D96N mutations (52%/10%) had 0.97 microU/gHb in PTPS erythrocyte activity. The PTPS erythrocyte activity did not coincide with the in-vitro PTPS activity based on patient genotype.- - - - - - - - - - ranking = 1keywords = error (Clic here for more details about this article) |
2/171. Long-term follow up of a new case of hawkinsinuria.Hawkinsinuria is a rarely diagnosed autosomal dominantly transmitted inborn error of tyrosine metabolism with impaired conversion of 4-hydroxyphenylpyruvate to homogentisate. As a consequence of the defective 4-hydroxyphenylpyruvate dioxigenase activity, large amounts of the unusual, ninhydrin-positive amino acid hawkinsin and later on in life 4-hydroxycyclohexylacetic acid are formed and excreted. Clinically the disease is characterised mainly by chronic metabolic acidosis and severe growth retardation as a result of protein overload. As the ability to form 4-hydroxycyclohexylacetic acid and thereby to cope with the still not very well defined reactive and toxic intermediates increases, clinical symptoms vanish. We report here a new patient with hawkinsinuria having experienced a series of admissions because of unclear hepatopathy, growth retardation, and renal tubular acidosis. CONCLUSION: Prolonged tyrosyluria in the newborn and young baby should cause the clinical chemist not only to exclude tyrosinaemia, galactosaemia, and fructose intolerance but also to look carefully for hawkinsin in the aminoacid chromatogram.- - - - - - - - - - ranking = 82.153845908508keywords = inborn error, metabolism, error (Clic here for more details about this article) |
3/171. Hypoketotic hypoglycemic coma in a 21-month-old child.We present the case of a 21-month-old child with hypoketotic hypoglycemic coma. The differential diagnosis initially included metabolic causes versus a toxicologic emergency (unripe ackee fruit poisoning). Using information obtained from the emergency department, the diagnosis was confirmed as the late-onset form of glutaric acidemia type II. This case illustrates the importance of emergency physicians in the diagnosis and management of children with inborn errors of metabolism.- - - - - - - - - - ranking = 82.153845908508keywords = inborn error, metabolism, error (Clic here for more details about this article) |
4/171. [13C]valine metabolism in methylmalonicacidemia using nuclear magnetic resonance: propinonate as an obligate intermediate.[Alpha-13C]- and [alpha,beta-13C]valine were administered sequentially to a patient with methylmalonicacidemia to clarify the metabolic pathway of valine from methylmalonic acid semialdehyde to methylmalonyl-CoA. methylmalonic acid was isolated from multiple urine samples, purified, and analyzed by 13C nuclear magnetic resonance spectroscopy. Contrary to the widely accepted view, the results show unequivocally that methylmalonic acid semialdehyde is decarboxylated to propionate before conversion to methylmalonyl CoA.- - - - - - - - - - ranking = 12.068582857505keywords = metabolism (Clic here for more details about this article) |
5/171. Effect of oral antibiotics on intestinal production of propionic acid.BACKGROUND: Propionic acid derived from colonic bacterial fermentation contributes substantially to overall propionate load in children with disorders of propionate metabolism, and its reduction is important for adequate metabolic control. AIMS: To evaluate the in vitro and in vivo effects of antibiotic treatment on propionate production by colonic bacteria, and plasma propionate concentrations in a child with propionic acidaemia. methods: in vitro fermentation techniques were used to study the effects of addition of antibiotics (metronidazole, clindamycin, erythromycin, and vancomycin) on net faecal production of short chain fatty acids including propionic acid. Courses of oral antibiotics of 7 days duration were used to assess the in vivo effects on faecal propionate production and metabolic control including plasma propionate concentrations. RESULTS: metronidazole produced the largest and most consistent reduction (77-84%) in the production in vitro of propionate from faecal homogenates. Oral administration of metronidazole reduced faecal propionate production by 43% within 24 hours of treatment; a 7 day course virtually eliminated it for the next 3 weeks. These reductions were accompanied by substantially lowered plasma propionate concentrations during the same period. CONCLUSIONS: Intermittent courses of oral metronidazole might be as effective as continuous treatment in reducing gut propionate production in children with disorders of propionate metabolism.- - - - - - - - - - ranking = 6.0342914287525keywords = metabolism (Clic here for more details about this article) |
6/171. 2-Methylbutyryl-coenzyme a dehydrogenase deficiency: a new inborn error of L-isoleucine metabolism.An 4-mo-old male was found to have an isolated increase in 2-methylbutyrylglycine (2-MBG) and 2-methylbutyrylcamitine (2-MBC) in physiologic fluids. in vitro oxidation studies in cultured fibroblasts using 13C- and 14C-labeled branched chain amino acids indicated an isolated block in 2-methylbutyryl-CoA dehydrogenase (2-MBCDase). Western blotting revealed absence of 2-MBCDase protein in fibroblast extracts; dna sequencing identified a single 778 C>T substitution in the 2-MBCDase coding region (778 C>T), substituting phenylalanine for leucine at amino acid 222 (L222F) and absence of enzyme activity for the 2-MBCDase protein expressed in escherichia coli. prenatal diagnosis in a subsequent pregnancy suggested an affected female fetus, supporting an autosomal recessive mode of inheritance. These data confirm the first documented case of isolated 2-MBCDase deficiency in humans.- - - - - - - - - - ranking = 328.61538363403keywords = inborn error, metabolism, error (Clic here for more details about this article) |
7/171. Molecular characterization of methylmalonate semialdehyde dehydrogenase deficiency.Three patients have been reported with (putative) methylmalonic semialdehyde dehydrogenase (MMSDH) deficiency. The urine metabolic pattern was strikingly different in all, including beta-alanine, 3-hydroxypropionic acid, both isomers of 3-amino- and 3-hydroxyisobutyric acids in one and 3-hydroxyisobutyric and lactic acids in a second, and mild methylmalonic aciduria in a third patient. In an effort to clarify these disparate metabolite patterns, we completed the cDNA structure, and characterized the genomic structure of human MMSDH gene in order to undertake molecular analysis. Only the first patient had alterations in the MMSDH coding region, revealing homozygosity for a 1336G > A transversion, which leads to substitution of arginine for highly conserved glycine at amino acid 446. No abnormalities of the MMSDH cDNA were detected in the other patients. These data provide the first molecular characterization of an inborn error of metabolism specific to the L-valine catabolic pathway.- - - - - - - - - - ranking = 82.153845908508keywords = inborn error, metabolism, error (Clic here for more details about this article) |
8/171. Progressive infantile neurodegeneration caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: a novel inborn error of branched-chain fatty acid and isoleucine metabolism.We report a novel inborn error of metabolism identified in a child with an unusual neurodegenerative disease. The male patient was born at term and recovered well from a postnatal episode of metabolic decompensation and lactic acidosis. Psychomotor development in the first year of life was only moderately delayed. After 14 mo of age, there was progressive loss of mental and motor skills; at 2 years of age, he was severely retarded with marked restlessness, choreoathetoid movements, absence of directed hand movements, marked hypotonia and little reaction to external stimuli. Notable laboratory findings included marked elevations of urinary 2-methyl-3-hydroxybutyrate and tiglylglycine without elevation of 2-methylacetoacetate, mild elevations of lactate in CSF and blood, and a slightly abnormal acylcarnitine profile. These abnormalities became more apparent after isoleucine challenge. Enzyme studies showed absent activity of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) in the mitochondrial oxidation of 2-methyl branched-chain fatty acids and isoleucine. Under dietary isoleucine restriction, neurologic symptoms stabilized over the next 7 months.- - - - - - - - - - ranking = 410.76922954254keywords = inborn error, metabolism, error (Clic here for more details about this article) |
9/171. Localized proton MR spectroscopy in infants with urea cycle defect.SUMMARY: urea cycle defect is an inborn error of ammonium metabolism caused by a deficient activity of the enzymes involved in urea synthesis. Localized short-TE proton MR spectroscopy, performed in two infants who had citrullinemia and ornithine transcarbamylase deficiency, respectively, showed a prominent increase of glutamine/glutamate and lipid/lactate complex in both cases. N-acetylaspartate, total creatine, and myo-inositol were decreased in the infant with citrullinemia. Proton MR spectroscopy provided useful information for the diagnosis and understanding of the pathophysiology of urea cycle enzyme defect.- - - - - - - - - - ranking = 82.153845908508keywords = inborn error, metabolism, error (Clic here for more details about this article) |
10/171. plasma amino acid and urine organic acid analyses of methylmalonic acidemia in a Thai infant.Methylmalonic acidemia is an inborn error of organic acid metabolism resulting from defects in methylmalonyl CoA mutase. Analysis of plasma free amino acids in a 15-month-old Thai infant by HPLC showed marked elevation of glycine. HPLC analysis of urinary organic acids showed high levels of methylmalonic acid.- - - - - - - - - - ranking = 82.153845908508keywords = inborn error, metabolism, error (Clic here for more details about this article) |
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