1/53. Isovaleric acidemia with promyelocytic myeloproliferative syndrome.Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl-coenzyme a dehydrogenase deficiency and is one of the branched-chain aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to coma and death in the first 2 months of life. This report concerns an infant who presented at 10 days of age because of lethargy, poor feeding, hypothermia, cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. death occurred at 19 days of age. autopsy showed mild fatty change in the liver and extramedullary hematopoiesis, generalized escherichia coli sepsis, and myelodysplasia of the bone marrow with arrest of the myeloid series at the promyelocytic stage. The appearance resembled promyelocytic leukemia, but the diagnostic 15:17 translocation was not present. The maturation arrest in granulopoiesis in isovaleric acidemia appears to be most likely due to a direct metabolic effect on granulocyte precursor cells.- - - - - - - - - - ranking = 1keywords = coma (Clic here for more details about this article) |
2/53. 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 = 5keywords = coma (Clic here for more details about this article) |
3/53. diagnosis of Japanese patients with HHH syndrome by molecular genetic analysis: a common mutation, R179X.patients with mitochondrial ornithine transporter deficiency (or HHH syndrome) present with various neurological symptoms, including mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia, and episodic disturbance of consciousness or coma due to hyperammonemia. We previously described three novel mutations in the ORNT1 gene in Japanese patients with HHH syndrome. In this article, we report a new patient with HHH syndrome, a 52-year-old woman, who had the typical clinical features, except for an absence of mental retardation. When we screened this patient, as well as a previously described Japanese patient, for mutations in the ORNT1 gene, we found that both were homozygous for a nonsense mutation (R179X). Furthermore, reverse transcription (RT)-polymerase chain reaction (PCR) of fibroblast rna from one patient showed exon 4 skipping, as had been observed in a previously reported patient with R179X. These results, together with the findings in our previous report, show that, in three of our five reported Japanese HHH patients (six of ten alleles), R179X is present, suggesting that this is a common mutation in Japanese patients with HHH syndrome.- - - - - - - - - - ranking = 1keywords = coma (Clic here for more details about this article) |
4/53. carbamyl phosphate synthetase-1 deficiency discovered after valproic acid-induced coma.valproic acid induced coma is presented in an adult patient without a history of metabolic disease. liver biopsy revealed a reduction in activity of carbamyl phosphate synthetase-I, an enzyme obligated for transformation of ammonia to urea in the urea cycle. After recovery CT scan follow-up showed marked cerebral atrophy which did not exist prior to the state of coma. risk factors are discussed.- - - - - - - - - - ranking = 6keywords = coma (Clic here for more details about this article) |
5/53. propionic acidemia: unusual course with late onset and fatal outcome.A 4 1/2-year-old girl with a so far unremarkable medical history became comatose during a simple infection. She showed severe metabolic acidosis without elevation of lactate. In blood the branched-chain amino acids were increased. In urine ketone-bodies, increased 3-OH-isovaleric and 3-OH propionic acid excretion were detected, while methylmalonate was not found. The profile of acylcarnitines revealed increased propionylcarnitine. Despite restriction of protein supply, high-caloric nutrition, correction of acidosis, and supplementation of biotin and carnitine, the girl died 2 days after admission due to arrhythmia of the heart. In skin fibroblasts the activity of propionyl-coenzyme a carboxylase (PCC) was markedly decreased. mutation analysis confirmed the diagnosis of propionic acidemia (PA) with compound heterozygosity for 2 new missense mutations L417W/Q293E in the PCCA gene, with the mother carrying the Q293E and the father the L417W mutation. Late-onset PA should be included in the differential diagnosis of unclear coma. Determination of the acylcarnitines using tandem mass spectrometry as well as organic acids in urine is recommended.- - - - - - - - - - ranking = 2keywords = coma (Clic here for more details about this article) |
6/53. Lysinuric protein intolerance presenting deficiency of argininosuccinate synthetase.A 35-yr-old woman, who suffered from relapsing coma with hyperammonemia for 17 yr, was diagnosed to have lysinuric protein intolerance (LPI). Increased urinary dibasic amino acids (lysine, arginine and ornithine) and impaired absorption of orally administered lysine and arginine proved the defects of renal tubular and intestinal transport of dibasic amino acids. These defects are the primary cause of impaired urea cycle metabolism in LPI. Further, the level of argininosuccinate synthetase (ASS), a urea cycle enzyme, was analyzed and it was found to be below the normal level. This is the second reported case of LPI presenting ASS deficiency.- - - - - - - - - - ranking = 1keywords = coma (Clic here for more details about this article) |
7/53. A patient with propionic acidemia managed with continuous insulin infusion and total parenteral nutrition.An infant newly diagnosed with propionic acidemic coma was managed successfully with total parenteral nutrition (TPN) and continuous infusion of insulin. The urinary excretion of 3-hydroxypropionic acid was reduced to 3% of the admission value in 4 days, gradually decreasing to 1.5% in 16 days. The treatment did not prevent a prolonged episode of thrombocytopenia. The infant tolerated TPN well, except for continued hyper-lactic acidemia (2 to 4 times normal). Metabolic acidosis and mild hyperammonemia recurred only when the patient had sepsis secondary to candida albicans and staphylococcus aureus infection.- - - - - - - - - - ranking = 1keywords = coma (Clic here for more details about this article) |
8/53. A homozygous nonsense mutation in the methylmalonyl-CoA epimerase gene (MCEE) results in mild methylmalonic aciduria.Methylmalonic aciduria (MMA-uria) is an autosomal recessive inborn error of amino acid metabolism, involving valine, threonine, isoleucine, and methionine. This organic aciduria may present in the neonatal period with life-threatening metabolic acidosis, hyperammonemia, feeding difficulties, pancytopenia, and coma. Most affected patients have mutations in the methylmalonyl-coenzyme a (methylmalonyl-CoA) mutase gene. Mildly affected patients may present in childhood with failure to thrive and recurrent attacks of metabolic acidosis. Both a higher residual activity of methylmalonyl-coa mutase as well as the vitamin B12-responsive defects (cblA and cblB) may form the basis of the mild disorder. A few patients with moderate MMA-uria are known in whom no defect could be identified. Here we present a 16-year-old female patient with persisting moderate MMA-uria (approximately 50 mmol/mol creatinine). She was born to consanguineous Caucasian parents. Her fibroblast mutase activity was normal and no effect of vitamin B12 supplementation could be established. Reduced incorporation of 14C-propionate into macromolecules suggested a defect in the propionate-to-succinate pathway. We found a homozygous nonsense mutation (c.139C>T) in the methylmalonyl-CoA epimerase gene (MCEE), resulting in an early terminating signal (p.R47X). Both parents were heterozygous for this mutation; they were found to excrete normal amounts of methylmalonic acid (MMA). This is the first report of methylmalonyl-CoA epimerase deficiency, thereby unequivocally demonstrating the biochemical role of this enzyme in human metabolism.- - - - - - - - - - ranking = 1keywords = coma (Clic here for more details about this article) |
9/53. Fatal hyperammonemia resulting from a C-to-T mutation at a MspI site of the ornithine transcarbamylase gene.ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle in humans and is responsible for lethal neonatal hyperammonemia in males. Partial OTC deficiency also occurs in females and can be responsible for life-threatening hyperammonemic comas in heterozygotes. The cosegregation of the trait with a 5.8-kb abnormal MspI fragment in an affected family led us to hypothesize that this unexpected migration pattern was related to the mutation event in this particular family. Using polymerase chain reaction amplification of the specific mRNA derived from a post-mortem biopsy of the liver, we found that the MspI site located in the seventh exon of the gene was abolished and we finally identified a C-to-T transition at codon 225 of the cDNA, changing a proline to a leucine in the protein. Subsequent digestion of amplified exon 7 using the restriction enzyme MspI allowed direct screening for the mutant genotype during the next pregnancy. The present study supports the view that direct detection of the mutant genotype using either Southern blotting or digestion of amplified exons of the gene can contribute to genetic counselling in noninformative families. Finally, since MspI digestions are routinely performed for restriction fragment length polymorphism-based family studies in OTC deficiency, we suggest that the possible presence of the 5.8-kb abnormal fragment should be investigated on Southern blots of affected individuals.- - - - - - - - - - ranking = 1keywords = coma (Clic here for more details about this article) |
10/53. A case of citrullinemia with abnormal messenger rna for argininosuccinate synthetase.A male neonate, thus far healthy and fed with breast milk, developed rapidly increasing apathy on the third day of life. Sucking became poor and hyperhidrosis was present. hyperammonemia (3,305 micrograms/dl) was noted. He became comatose and died on the fourth day. There was a profound derangement of amino acid concentration in the body fluids, with highly elevated citrulline levels (4.70 mumols/ml in serum and 8.47 mumols/ml in urine). autopsy showed diffuse pulmonary bleeding, as the only noteworthy pathological finding. The liver contained no detectable argininosuccinate synthetase (ASS) activity. The defect of ASS in the present case was not due to a reduced amount of ASSmRNA, but its structure was found to be abnormal; it was approximately 1.57 kb in length due to a defect of about 0.1 kb near the 3' end of the coding region.- - - - - - - - - - ranking = 1keywords = coma (Clic here for more details about this article) |
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