1/7. 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 = fatty (Clic here for more details about this article) |
2/7. Scintigraphic evaluation of cardiac metabolism in multicentric Castleman's disease.A 72-year-old woman had insidious onset of heart failure, and was diagnosed as multicentric Castleman's disease. She underwent myocardial imaging with technetium-99m tetrofosmin, 1-123 beta-methyl-iodophenyl pentadecanoic acid (BMIPP). technetium-99m tetrofosmin studies showed almost normal uptake of the left ventricular myocardium indicating normal myocardial perfusion. 1-123 BMIPP showed reduced uptake in the apical segment of the myocardium, indicating regional fatty acid metabolic abnormalities.- - - - - - - - - - ranking = 1keywords = fatty (Clic here for more details about this article) |
3/7. 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 = 15.391665941161keywords = fatty liver, fatty (Clic here for more details about this article) |
4/7. Systemic triglyceride storage disease with normal carnitine: a putative defect in long-chain fatty acid metabolism.A 45-year-old Japanese man presented with lipid storage myopathy, fatty liver, cardiomyopathy, vacuolated leukocytes (Jordans' anomaly) and perceptive deafness. His parents were consanguineous and his younger sister was also affected. Histopathological and biochemical studies revealed an abnormal accumulation of triglyceride in muscle, liver, leukocytes, gastrointestinal endothelial cells and cultured skin fibroblasts. On electron microscopy, the vacuoles lacked limiting membranes and were adjacent to the mitochondria. Total and free carnitines in muscle were normal levels. Production rate of 14CO2 or acid-soluble [14C]metabolites from [1-14C]palmitate in the patient's cells was decreased to about 50% of that in control cells, whereas that from [1-14C]butyrate was normal. Long-chain fatty acyl esterase activities in the patient's leukocytes were normal at both pH 4.0 and pH 8.0. Despite the strong suggestion of an impaired metabolism of long-chain fatty acids, there were no evidences of abnormalities in carnitine metabolism or uptake of fatty acids into cells. The disorder is clinically different from defects in carnitine metabolism, defects in the carnitine-acylcarnitine translocase system or in mitochondrial beta-oxidation enzymes. Although the underlying metabolic defect has not been elucidated, this disease seems to be an autosomal-recessively inherited disorder of systemic triglyceride storage, probably due to an impaired regulation of lipolysis and triacylglycerol synthesis.- - - - - - - - - - ranking = 22.391665941161keywords = fatty liver, fatty (Clic here for more details about this article) |
5/7. The prenatal diagnosis of adrenoleukodystrophy. Demonstration of increased hexacosanoic acid levels in cultured amniocytes and fetal adrenal gland.amniocentesis was performed in two women heterozygous for adrenoleukodystrophy (ALD). One fetus was male, and the hexacosanoic acid (C26) level in the cultured amniotic cells was 0.808 microgram per mg of protein, compared to 0.104 /- 0.069 (S.D.) in controls. pregnancy was interrupted at 22 wk gestation. The fetal adrenal cortex showed the ultrastructural inclusions characteristic of ALD and C26 accounted for 35% of the fatty acids in the cholesterol esters extracted from this tissue, more than one thousand times control. The second amniocentesis was performed in a woman who was also heterozygous for an electrophoretic variant of glucose 6- phosphate dehydrogenase (G6PD), and a member of a kindred showing genetic linkage of loci for ALD and G6PD. The fetus was female and the C26 level in cultured amniotic cells was 0.577. pregnancy was interrupted at 11 wk for reasons unrelated to ALD. Study of C26 level and G6PD type in cultured fetal tissues confirmed heterozygosity for ALD.- - - - - - - - - - ranking = 1keywords = fatty (Clic here for more details about this article) |
6/7. Multisystem triglyceride storage disorder with impaired long-chain fatty acid oxidation.A five-year-old girl presented with congenital ichthyosis, hepatosplenomegaly, vacuolized granulocytes (Jordans' anomaly), and myopathy. Pathological, ultrastructural, and biochemical studies revealed nonlysosomal, multisystemic triglyceride storage. The cultured fibroblasts had increased uptake but decreased oxidation of labeled oleate. The patient failed to produce ketone bodies on fasting. A medium-chain triglyceride diet reversed the hepatomegaly. These studies are all consistent with a partial defect in the catabolism of long-chain fatty acids. This newly identified syndrome is presumably transmitted as an autosomal recessive trait.- - - - - - - - - - ranking = 5keywords = fatty (Clic here for more details about this article) |
7/7. 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 = 4keywords = fatty (Clic here for more details about this article) |