1/5. Inherited metabolic disorders in thailand.The study of inborn errors of metabolism (IEM) in thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical genetics Unit, Department of pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn research Institute) and abroad (japan and the united states). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in thailand, research and pilot studies in newborn screening in thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
2/5. 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 = 1keywords = cycle (Clic here for more details about this article) |
3/5. Postpartum "psychosis" in mild argininosuccinate synthetase deficiency.BACKGROUND: urea cycle disorders are relatively rare but well-established causes of postpartum coma and death. Such clinical presentations have been reported previously in ornithine transcarbamylase and carbamyl phosphate synthetase deficiencies. CASE: We describe a woman, without prior symptoms of metabolic disease, who presented with hyperammonemia and psychiatric symptoms in the postpartum period. Initial diagnoses included acute fatty liver of pregnancy and postpartum psychosis. She was later found to have argininosuccinate synthetase deficiency after further metabolic investigations. Rare heterozygous mutations in the argininosuccinate synthetase gene were identified. CONCLUSION: urea cycle disorders may present initially with postpartum psychiatric symptoms and may represent an underrecognized cause of "postpartum psychosis." We recommend obtaining metabolic studies in women with neurologic or severe psychiatric symptoms in the postpartum period.- - - - - - - - - - ranking = 2keywords = cycle (Clic here for more details about this article) |
4/5. argininosuccinic aciduria: clinical and biochemical findings in three children with the late onset form, with special emphasis on cerebrospinal fluid findings of amino acids and pyrimidines.Three children with the late onset form of argininosuccinic aciduria are presented. The first two are sisters. The clinical features are characterized by mild retardation and ataxia, complicated by episodes of hyperammonemia. All patients showed elevated concentrations of argininosuccinic acid and its anhydrides in all body fluids, most pronounced in cerebrospinal fluid (CSF). Moreover, in Cases 1 and 2, we found elevated concentrations of pseudouridine and uridine limited to CSF, which was not reported before. In Case 3, with some residual activity of argininosuccinate lyase (ASL), we found normal values of these compounds. In urine we found elevated concentrations of uracil in Cases 1 and 2, and orotic acid in Case 2. plasma showed an elevated concentration of orotic acid in all three patients, uracil was elevated in Case 2, cytidine was elevated in Cases 2 and 3. The results are being discussed and indicate that CSF values of pyrimidines reveal new biochemical abnormalities of brain tissue in urea cycle disorders.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
5/5. Medium chain 3-ketoacyl-coenzyme a thiolase deficiency: a new disorder of mitochondrial fatty acid beta-oxidation.A Japanese male neonate died at 13 d of age after presenting at 2 d of age with vomiting, dehydration, metabolic acidosis, liver dysfunction, and terminal rhabdomyolysis with myoglobinuria. Multiple urine organic acid analyses consistently revealed a markedly elevated excretion of lactic acid, 3-hydroxybutyric acid, and saturated and unsaturated C6-C16 dicarboxylic acids, with predominant C12-C16 species. Oxidation of [1-14C]octanoic acid in cultured skin fibroblasts was significantly reduced (0.59 nmol/h/mg of protein; controls, 1.93 /- 0.65), [1-14C]palmitic acid oxidation was 1.11 nmol/h/mg of protein (controls, 1.63 /- 0.41). A systematic study of the catalytic activities of nine enzymes of the beta-oxidation cycle using the respective optimal substrate revealed a deficiency of a single enzyme not previously associated with a metabolic disorder, medium chain 3-ketoacyl-CoA thiolase (patient, 3.9 nmol/min/mg protein; controls (n = 6), 10.2 /- 2.3). immunoprecipitation with antibodies raised against medium chain 3-ketoacyl-CoA thiolase revealed a 60% decrease compared with controls.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |