1/24. Sequence variations in the flavin-containing mono-oxygenase 3 gene (FMO3) in fish odour syndrome.Trimethylaminuria is inherited recessively as a defect in hepatic N-oxidation of dietary derived trimethylamine (TMA) which causes excess excretion of TMA so that affected individuals have a body odour resembling rotten fish. Flavin-containing mono-oxygenase 3 (FMO3) catalyses TMA oxidation and mutations in the FMO3 gene have recently been shown to underlie trimethylaminuria/fish odour syndrome. We searched for FMO3 mutations in a previously unreported individual with this disorder using polymerase chain reaction of genomic dna, heteroduplex analysis and direct sequencing of heteroduplex band shifts. We identified a heterozygous missense Pro153-->Leu153 mutation in exon 4. Leu153 has been reported previously as a homozygous mutation in two unrelated siblings with trimethylaminuria and has been shown to result in total loss of FMO3 enzyme activity. In our patient, two further missense mutations were identified on the other FMO3 allele, Val143-->Glu143 and Glu158-->Lys158. Lys158 is known to be a common polymorphism, but has functional significance in reducing enzyme activity by 10%. Glu143 has not been documented previously, but was shown to be a rare polymorphism and may be of further relevance in reducing FMO3 activity. mutagenesis studies and enzyme assays will be necessary to confirm or refute the potential pathogenic significance of Glu143 in this patient, but the mutation Pro153-->Leu153 appears to be a recurrent cause of this distressing metabolic disorder.- - - - - - - - - - ranking = 1keywords = enzyme (Clic here for more details about this article) |
2/24. Persistent hyperlipasemia caused by macrolipase in an adolescent.serum amylase and lipase frequently rise during bouts of acute pancreatitis, and measurement of these enzymes provides important diagnostic information. We report a pediatric patient with persistent elevations of serum lipase resulting from macrolipasemia, a complex of lipase with IgG, rather than pancreatitis.- - - - - - - - - - ranking = 0.33333333333333keywords = enzyme (Clic here for more details about this article) |
3/24. heterozygote ornithine transcarbamylase deficiency presenting as symptomatic hyperammonemia during initiation of valproate therapy.ornithine transcarbamylase is a mitochondrial urea cycle enzyme. women with heterozygous ornithine transcarbamylase deficiency may have no symptoms or have episodic, symptomatic hyperammonemia, which can be fatal. We report a previously undiagnosed heterozygote ornithine transcarbamylase-deficient patient who had symptomatic hyperammonemia during initiation of valproate therapy. This is the second such patient reported. Symptomatic hyperammonemia during valproate therapy may indicate ornithine transcarbamylase deficiency. Since valproate inhibits ureagenesis and can be toxic to mitochondria, it should be used extremely cautiously, or not at all, in ornithine transcarbamylase-deficient patients.- - - - - - - - - - ranking = 0.33333333333333keywords = enzyme (Clic here for more details about this article) |
4/24. fibrinogen storage disease without hypofibrinogenemia associated with estrogen therapy.BACKGROUND: Cytoplasmic inclusion bodies within hepatocytes may have different etiologies, including the endoplasmic reticulum Storage Diseases (ERSDs). ERSD is a pathological condition characterized by abnormal accumulation of proteins destined for secretion in the endoplasmic reticulum of hepatocytes; it may be congenital (primary) or acquired (secondary). fibrinogen storage disease is a form of ERSD. CASE PRESENTATION: We present a case of fibrinogen storage disease secondary to estrogen replacement therapy. Its causal relationship to the drug is shown by histological, immunohistochemical and ultrastructural studies of paired liver biopsies obtained during and after the drug therapy. CONCLUSION: The liver biopsies of patients with idiopathic liver enzyme abnormalities should be carefully evaluated for cytoplasmic inclusion bodies and, although rare, fibrinogen deposits.- - - - - - - - - - ranking = 1262.8577472772keywords = storage disease, storage, enzyme (Clic here for more details about this article) |
5/24. A poor metabolizer for cytochromes P450 2D6 and 2C19: a case report on antidepressant treatment.Scientific literature has never described a poor metabolizer for both the cytochrome P450 (CYP) 2D6 and the CYP 2C19. They are expected to be rare (<1% in different ethnic groups) and prone to adverse drug reactions with many antidepressants. In an ongoing pharmacogenetic study, after genotyping 1,576 subjects in three kentucky state hospitals we have found one poor metabolizer for both CYP 2D6 and CYP 2C19, which corresponds to a prevalence of 0.06% (95% CI 0.01 to 0.36). The naturalistic antidepressant treatment of this poor metabolizer for both enzymes is described in this article. As genotyping reaches clinical practice, it will be interesting to prospectively establish whether mirtazapine is a reasonable choice as an antidepressant for these patients, as the data and this case suggest.- - - - - - - - - - ranking = 0.33333333333333keywords = enzyme (Clic here for more details about this article) |
6/24. 3-Methylcrotonyl-CoA carboxylase deficiency: metabolic decompensation in a noncompliant child detected through newborn screening.We report a 19-month-old girl with a 3-methylcrotonyl-coenzyme a carboxylase deficiency that was detected through newborn screening. She was treated for the first 12 months but was lost to follow-up after the initial year. Her parents did not comply with the recommendations for management during periods of illness or for regular medical evaluations. During an acute illness, she presented with severe acidosis, hypoglycemia, and a low plasma carnitine level at 19 months of age. This report highlights the importance of more extensive follow-up plans to improve parental compliance.- - - - - - - - - - ranking = 0.33333333333333keywords = enzyme (Clic here for more details about this article) |
7/24. Normalization of short-chain acylcoenzyme A dehydrogenase after riboflavin treatment in a girl with multiple acylcoenzyme A dehydrogenase-deficient myopathy.A 12-year-old girl was shown to have carnitine-deficient lipid storage myopathy and organic aciduria compatible with multiple acylcoenzyme A (acyl-CoA) dehydrogenase deficiency. In muscle mitochondria, activities of both short-chain acyl-coa dehydrogenase (SCAD) and medium-chain acyl-coa dehydrogenase (MCAD) were 35% of normal. antibodies against purified SCAD, MCAD, and electron-transfer flavoprotein were used for detection of cross-reacting material (CRM) in the patient's mitochondria. Western blot analysis showed absence of SCAD-CRM, reduced amounts of MCAD-CRM, and normal amounts of electron-transfer flavoprotein-CRM. The patient, who was unresponsive to treatment with oral carnitine, improved dramatically with daily administration of 100 mg oral riboflavin. Increase in muscle bulk and strength and resolution of the organic aciduria were associated with normalization of SCAD activity and "reappearance" of SCAD-CRM. In contrast, both MCAD activity and MCAD-CRM remained lower than normal. These results suggest that in some patients with multiple acyl-coa dehydrogenase deficiency riboflavin supplementation may be effective in restoring the activity of SCAD, and possibly of other mitochondrial flavin-dependent enzymes.- - - - - - - - - - ranking = 31.138859727303keywords = storage, enzyme (Clic here for more details about this article) |
8/24. Infantile sialic acid storage disease associated with renal disease.A child with infantile sialic acid storage disease is reported. ultrasonography demonstrated fetal ascites. At birth, the infant appeared hydropic and presented with numerous dysmorphic features, including sparse white hair, coarse facies, hypertelorism, epicanthal folds, anteverted nostrils, and a long philtrum. In addition, he had visceromegaly, bilateral inguinal hernias, and a slight gibbus deformity. lymphocytes were vacuolated and bone marrow contained large numbers of foam cells. There were generalized vacuolations of both reticuloendothelial and parenchymal cells in the examined tissues. Neuropathologic studies revealed wide-spread neuronal storage, myelin loss, axonal spheroids, and gliosis. neurons, endothelial cells, and kupffer cells stained with wheat germ agglutinin indicated an accumulation of sialic acid. Free sialic acid was significantly increased in urine and serum, as well as in liver, heart, and brain tissues. The alpha-neuraminidase activity was normal. It is assumed that the basic defect of infantile sialic acid storage disease lies in impaired transport of sialic acid across the lysosomal membrane.- - - - - - - - - - ranking = 1290.3299403378keywords = storage disease, storage (Clic here for more details about this article) |
9/24. Fatal copper storage disease of the liver in a German infant resembling Indian childhood cirrhosis.A female child of non-consanguineous, healthy German parents fell ill at the age of 7 months with a progressive liver disease leading to irreversible hepatic failure 3 months later. Histological examination revealed severe liver cell necrosis, excessive Mallory body formation and veno-occlusive-like changes associated with massive storage of copper, similar to Indian childhood cirrhosis (ICC). Chronic copper contamination of drinking water was the only detectable aetiological factor. The study illustrates that ICC most probably is an environmental disease, also occurring outside the Indian subcontinent, and is likely to be underdiagnosed in the western world.- - - - - - - - - - ranking = 869.48846902319keywords = storage disease, storage (Clic here for more details about this article) |
10/24. Lipid storage myopathy due to glutaric aciduria type II: treatment of a potentially fatal myopathy.Several patients with lipid storage myopathies have been described, although in most cases the biochemical defect is unclear. A child is reported who presented with severe muscle weakness at age six months. She had lipid storage myopathy due to glutaric aciduria type II. It is probable that her brother died from the same disorder at the age of three months. She has responded well to treatment with a low-fat diet, riboflavin, carnitine and glycine.- - - - - - - - - - ranking = 166.83315836382keywords = storage (Clic here for more details about this article) |
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