1/176. Defect in dimethylglycine dehydrogenase, a new inborn error of metabolism: NMR spectroscopy study.BACKGROUND: A38-year-old man presented with a history of fish odor (since age 5) and unusual muscle fatigue with increased serum creatine kinase. Our aim was to identify the metabolic error in this new condition. methods: We used 1H NMR spectroscopy to study serum and urine from the patient. RESULTS: The concentration of N, N-dimethylglycine (DMG) was increased approximately 100-fold in the serum and approximately 20-fold in the urine. The presence of DMG as a storage product was confirmed by use of 13C NMR spectroscopy and gas chromatography-mass spectrometry. The high concentration of DMG was caused by a deficiency of the enzyme dimethylglycine dehydrogenase (DMGDH). A homozygous missense mutation was found in the DMGDH gene of the patient. CONCLUSIONS: DMGDH deficiency must be added to the differential diagnosis of patients complaining of a fish odor. This deficiency is the first inborn error of metabolism discovered by use of in vitro 1H NMR spectroscopy of body fluids.- - - - - - - - - - ranking = 1keywords = storage, enzyme (Clic here for more details about this article) |
2/176. Pancreatic cancer and fibrinogen storage disease.BACKGROUND: Ductal adenocarcinoma is the most common type of pancreatic carcinoma while squamous, carcinosarcoma, sarcoma, giant cell carcinoma, and clear cell types are all rare. Hepatocellular fibrinogen storage disease is also an uncommon disorder which may be associated with hepatocellular carcinoma. Two cases of pancreatic carcinoma were encountered in a family with fibrinogen storage disease, further raising the possibility of a predilection to malignancy in this unusual disorder. The tumour in one case was of the rare clear cell type. These two cases are the basis for this report. methods: Sections were cut from retrieved paraffin embedded tissue and stained for routine histology. immunohistochemistry using the avidin-biotin technique was applied for the expression of the markers p53 (D07), carcinoembryonic antigen (CEA), c-erbB-2, epithelial membrane antigen (EMA), and alpha-fetoprotein (AFP). RESULTS: Both cases were adenocarcinoma of pancreatic ductal origin. The tumour in one case showed features of a clear cell carcinoma. The tumour cells expressed p53, CEA, and EMA immunoreactivity and were negative for c-erbB-2 and AFP. CONCLUSIONS: Hepatocellular fibrinogen storage disease is rare and has been described in association with chronic hepatitis, cirrhosis, and rarely with hepatocellular carcinoma. This represents the first report of its association with carcinoma outside of the liver.- - - - - - - - - - ranking = 33.445607036491keywords = storage disease, storage (Clic here for more details about this article) |
3/176. An inborn error of bile acid synthesis (3beta-hydroxy-delta5-C27-steroid dehydrogenase deficiency) presenting as malabsorption leading to rickets.Deficiency of 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta-HSDH), the enzyme that catalyses the second reaction in the principal pathway for the synthesis of bile acids, has been reported to present with prolonged neonatal jaundice with the biopsy features of neonatal hepatitis. It has also been shown to present between the ages of 4 and 46 months with jaundice, hepatosplenomegaly, and steatorrhoea (a clinical picture resembling progressive familial intrahepatic cholestasis). This paper reports two children with 3beta-HSDH deficiency who developed rickets during infancy and did not develop clinically evident liver disease until the age of 3 years. bile acid replacement resulted in considerable clinical and biochemical improvement. The importance of thorough investigation of fat soluble vitamin deficiencies in infancy is emphasised.- - - - - - - - - - ranking = 0.25678445424863keywords = enzyme (Clic here for more details about this article) |
4/176. A severely affected infant with absence of cysteinyl leukotrienes in cerebrospinal fluid: further evidence that leukotriene c4-synthesis deficiency is a new neurometabolic disorder.leukotrienes are potent oxygenated metabolites derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. They comprise the cysteinyl leukotrienes (LTC4, LTD4, LTE4) and LTB4. The rate limiting step in the formation of cysteinyl leukotrienes is the conversion of LTA4 to LTC4 catalyzed by the enzyme LTC4 synthase. Recently, the first inborn error of leukotriene synthesis, LTC4-synthesis deficiency, has been identified in a patient with a fatal developmental syndrome. We report on an additional infant presenting with severe muscular hypotonia, symmetrical extension in the lower extremities and psychomotor retardation who died at the age of 6 months. Despite intensive investigations no specific diagnosis could be made. leukotrienes were subsequently analyzed in the cerebrospinal fluid. Concentrations of LTC4, LTD4 and LTE4 were below the detection limit (< 5 pg/ml) whereas LTB4 was found to be in the upper normal range. The absence of cysteinyl leukotrienes with normal LTB4 concentration in cerebrospinal fluid is unique and seems to be pathognomonic for LTC4-synthesis deficiency. Our patient most likely represents the second case described so far with this condition. This report provides further evidence that LTC4-synthesis deficiency represents a new neurometabolic disorder.- - - - - - - - - - ranking = 0.25678445424863keywords = enzyme (Clic here for more details about this article) |
5/176. A unique case of derangement of vitamin B12 metabolism.The case is described of a child, age 6 1/2 years, with retarded mental development, mild neurological signs and abnormal metabolism of sulphur-containing amino acids and methylmalonate, due to an inborn error in the formation of vitamin B12 coenzymes. The patient was treated for almost three years with hydroxycobalamin, folic acid, pyridoxine and choline. Though physical growth was normal, she continued to demonstrate a moderate degree of mental retardation. A brother of the patient died at the age of 5 years, probably of a similar, but undiagnosed, disorder. As far as we are aware there are only four other reported cases similar to the case described here. Two of these patients died and in other other two the defect was so mild that no treatment was necessary and who, in fact, showed appreciable improvement during the follow-up period, which to date amounts to 3 years and 3 months. For reasons detailed in the discussion, it is suggested that the diagnosis of homocystinuria is not complete until studies of folate and vitamin B12 metabolism are undertaken at the same time, so as to identify the metabolic defect(s) responsible for the condition.- - - - - - - - - - ranking = 0.25678445424863keywords = enzyme (Clic here for more details about this article) |
6/176. Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme.Sialuria is a rare inborn error of metabolism characterized by cytoplasmic accumulation and increased urinary excretion of free n-acetylneuraminic acid (NeuAc, sialic acid). Overproduction of NeuAc is believed to result from loss of feedback inhibition of uridinediphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc 2-epimerase) by cytidine monophosphate-n-acetylneuraminic acid (CMP-Neu5Ac). We report the cloning and characterization of human UDP-GlcNAc 2-epimerase cDNA, with mutation analysis of three patients with sialuria. Their heterozygote mutations, R266W, R266Q, and R263L, indicate that the allosteric site of the epimerase resides in the region of codons 263-266. The heterozygous nature of the mutant allele in all three patients reveals a dominant mechanism of inheritance for sialuria.- - - - - - - - - - ranking = 1.0271378169945keywords = enzyme (Clic here for more details about this article) |
7/176. Multiple acyl-coenzyme a dehydrogenase deficiency: diagnosis by acyl-carnitine analysis of a 12-year-old newborn screening card.We report a family who experienced an unexplained neonatal death. Twelve years after the death, we retrospectively diagnosed multiple acyl-coenzyme a dehydrogenase deficiency by demonstrating an abnormal acyl-carnitine profile in the child's archived newborn screening card, using tandem mass spectrometry.- - - - - - - - - - ranking = 1.2839222712431keywords = enzyme (Clic here for more details about this article) |
8/176. hyperinsulinism-hyperammonemia syndrome caused by mutant glutamate dehydrogenase accompanied by novel enzyme kinetics.hyperinsulinism-hyperammonemia syndrome (HHS) is a recently identified genetic disorder characterized by hyperinsulinemic hypoglycemia with concomitant hyperammonemia. In patients with HHS, activating mutations in the glutamate dehydrogenase (GDH) gene have been identified. GDH is a key enzyme linking glutamate metabolism with the Krebs cycle and catalyzes the conversion of glutamate to alpha-ketoglutarate. The activity of GDH is controlled by allosteric inhibition by GTP and, so far, all the mutations of HHS patients have been located within the GTP-binding site. Characteristically, GDH from these individuals have therefore normal basal activity in conjunction with a loss of GTP inhibition. In this study, however, we have identified a novel variant GDH in a patient with a more severe form of HHS. The mutation is located outside the GTP-binding site and the patient's GDH shows consistently higher activity, even in the absence of allosteric effectors. These results further support the hypothesis that the activating mutation of GDH is the cause of HHS. The mechanism leading to the activation of GDH, however, is not always related to the loss of GTP inhibition as was originally suggested.- - - - - - - - - - ranking = 1.2839222712431keywords = enzyme (Clic here for more details about this article) |
9/176. Recurrent nonimmune hydrops fetalis: a rare presentation of sialic acid storage disease.A case of recurrent hydrops fetalis, diagnosed on second trimester's ultrasonography, has led to the diagnosis of sialic acid storage disease. No classic etiology was found after the first accident. The recurrence in subsequent pregnancy raised the possibility of a storage disease that was confirmed by amniocentesis. The diagnosis of Salla's disease was based on high levels of free sialic acid in amniotic fluid and fetal cells culture and by specific histologic features on fetopathologic examination. diagnosis of inherited diseases is important because it implies a high risk of recurrence which makes mandatory genetic counseling and prenatal care in subsequent pregnancies.- - - - - - - - - - ranking = 28.667663174135keywords = storage disease, storage (Clic here for more details about this article) |
10/176. Atypical refsum disease with pipecolic acidemia and abnormal catalase distribution.We describe an 18-year-old patient with psychomotor retardation and abnormally short metatarsi and metacarpals but no other signs of classic refsum disease. Molecular analysis of the phytanoyl-coenzyme a hydroxylase gene revealed a homozygous deletion causing a frameshift. Surprisingly, L-pipecolic acid was elevated in plasma, and microscopy of the liver showed a reduced number of peroxisomes per cell and a larger average peroxisome size. These abnormal peroxisomes lacked catalase as did peroxisomes in fibroblasts of this patient. Such generalized peroxisomal abnormalities are not present in classic refsum disease.- - - - - - - - - - ranking = 0.25678445424863keywords = enzyme (Clic here for more details about this article) |
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