Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propionyl-CoA carboxylase (PCC) catalyzes the biotin-dependent carboxylation of propionyl-CoA to d-methylmalonyl-CoA in the mitochondrial matrix. Human PCC is a dodecamer composed of pairs of nonidentical alpha and beta subunits encoded by PCCA and PCCB genes, respectively. Deficiency of PCC results in propionic acidemia (PA), a metabolic disorder characterized by severe metabolic ketoacidosis, vomiting, lethargy, and hypotonia. To date, almost 60 mutations have been reported in both genes. Exon 15 of the beta subunit is one of the two sites where a number of mutations have been identified in PA patients. In the primary betaPCC sequence, these mutations lead to three substitutions (R512C, L519P, and N536D), three truncations (R499X, R514X, and W531X), and one insertion (A51_R514insP). We expressed these mutant proteins in Escherichia coli in which the GroESL complex was overexpressed. The only mutation that does not impact the stability of mutant betaPCC in bacteria is W531X. The remaining mutations lead to either complete (L519P, N536D) or partial (R499X, R512C, A513_R514insP, and R514X) degradation of the mutant subunits. Size-exclusion chromatography revealed that R512C and W531X do not affect the assembly of alphaPCC and betaPCC to active oligomers. Specific activities for these mutant proteins, however, were only 3.9 and 10% of the wild type, respectively. Taken together, the carboxyl-terminal portion of 40 amino acid residues of the beta subunit affects the stability and the assembly of the alpha and beta subunits as well as the carboxylation of propionyl-CoA.
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PMID:Changes in the carboxyl terminus of the beta subunit of human propionyl-CoA carboxylase affect the oligomer assembly and catalysis: expression and characterization of seven patient-derived mutant forms of PCC in Escherichia coli. 1113 55

Hyperammonemia associated with inherited disorders of amino acid and organic acid metabolism is usually manifested by irritability, somnolence, vomiting, seizures, and coma. Although the majority of these patients present in the newborn period, they may also present in childhood, adolescence, and adulthood with failure to thrive, persistent vomiting, developmental delay, or behavioral changes. Persistent hyperammonemia, if not treated rapidly, may cause irreversible neuronal damage. After the diagnosis of hyperammonemia is established in an acutely ill patient, certain diagnostic tests should be performed to differentiate between urea cycle defects and other causes of hyperammonemic encephalopathy. In a patient with a presumed inherited metabolic disorder, the aim of therapy should be to normalize blood ammonia levels. Recent experience has provided treatment guidelines that include minimizing endogenous ammonia production and protein catabolism, restricting nitrogen intake, administering substrates of the urea cycle, administering compounds that facilitate the removal of ammonia through alternative pathways, and, in severe cases, dialysis therapy. Initiation of dialysis in the encephalopathic patient with hyperammonemia is indicated if the ammonia blood level is greater than three to four times the upper limit of normal. Hemodialysis is the most effective treatment for rapidly reducing blood ammonia levels. Continuous hemofiltration and peritoneal dialysis are also effective modalities for reducing blood ammonia levels. An improved understanding of the metabolism of ammonia and neurological consequences of hyperammonemia will assist the nephrologist in providing optimal care for this high-risk patient population.
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PMID:Hyperammonemia in urea cycle disorders: role of the nephrologist. 1132 92

Despite the abundance of reports emerging in the literature on metabolic disorders, some disorders remain undiagnosed or misdiagnosed, not only in clinical pathology but also in forensic pathology. The authors report a patient who had recurrent episodes characterized by nausea, vomiting, and signs of dehydration necessitating admission to the hospital. At each admission, he was found to have lactic acidosis. On the first admission, glycolic acid was detected in his blood and he was diagnosed as having ethylene glycol intoxication. Only at the third admission, 2 years after the first, was the possibility of an underlying metabolic disorder considered. Laboratory investigations showed a deficiency of complex I in the mitochondrial oxidative phosphorylation. Possible medicolegal implications are discussed.
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PMID:An inherited metabolic disorder presenting as ethylene glycol intoxication in a young adult. 1195 4

Hypercalcemia is a common, life-threatening metabolic disorder that can be associated with cancer. Its pathophysiology includes enhanced osteoclastic bone resorption and decreased renal excretion of extracellular calcium. Symptoms of hypercalcemia include nausea, vomiting, bone pain, polyuria, renal insufficiency, bradycardia, and arrhythmia. The goals of medical therapy are to inhibit bone resorption and promote renal calcium excretion. Hydration is the first step in management. Treatments for hypercalcemia include phosphates, calcitonin, bisphosphonates, and gallium nitrate. Although intravenous phosphates prevent intestinal calcium absorption and inhibit mineral and bone matrix resorption, serious adverse events include renal failure, hypotension, extraskeletal calcification, and severe hypocalcemia. Calcitonin has a rapid onset of action and can lower serum calcium concentrations within hours, but its usefulness is limited by its short duration of effect and the development of tachyphylaxis. Bisphosphonates are effective inhibitors of bone resorption but appear to have decreased response rates in hypercalcemic patients with high levels of parathyroid-related protein. Gallium nitrate, an antitumor agent noncytotoxic to osteoclasts and bone cells, appears to be more effective than pamidronate, etidronate, and calcitonin in the treatment of cancer-related hypercalcemia. Importantly, unlike bisphosphonates, gallium nitrate is effective in both parathyroid-related protein-mediated and non-parathyroid-related protein-mediated hypercalcemia.
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PMID:Treatment of cancer-related hypercalcemia: the role of gallium nitrate. 1277 55

A previously healthy 5 1/2-year-old male had Reye syndrome. He presented in coma with apnea 1 week after a viral infection and following 2 days of vomiting and progressive obtundation. He was in coma with dystonic posturing and intact brainstem function. Laboratory evaluation revealed initial hypoglycemia, and markedly elevated liver enzymes, prolonged clotting times, and elevated ammonia levels. No underlying metabolic disorder was present, and the patient completely recovered. On a modified diffusion-weighted image magnetic resonance imaging scan, restriction of diffusion in the thalamus and midbrain was observed. While abnormalities of the thalamus and midbrain have previously been reported, this is the first report of diffusion-weighted imaging indicating early impairment of water diffusion, a finding more commonly observed with stroke.
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PMID:The thalamus and midbrain in Reye syndrome. 1664 4

Mitochondrial acetoacetyl-CoA thiolase deficiency (or beta-ketothiolase deficiency) is a rare metabolic disorder characterized by acute episodes of severe acidosis and ketosis. A case is presented of an 18-month-old boy who presented with vomiting and diarrhoea and was found to be markedly acidotic. When the acidosis persisted despite saline fluid boluses and bicarbonate correction, further investigations were undertaken. Routine biochemical investigation revealed detectable salicylate concentrations despite the parents denying its administration, which initially caused some diagnostic confusion. The results of urine organic acid analysis, however, confirmed that the diagnosis of mitochondrial acetoacetyl-CoA thiolase deficiency. The high concentrations of acetoacetate present in the patient's sample resulted in a false-positive reaction in the Trinder assay for salicylate.
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PMID:An unusual cause of interference in a salicylate assay caused by mitochondrial acetoacetyl-CoA thiolase deficiency. 1875 30

Propionic acidemia is a metabolic disorder (OMIM 606054) caused by deficiency of the propionyl-coenzyme A (CoA) carboxylase, which subsequently results in accumulation of propionic acid. Patients may initially present with poor feeding, vomiting, loss of appetite, hypotonia, and lethargy. Later, most children will show different degrees of motor, social and language delay even more serious medical problems, including heart abnormalities, seizures, coma, and possibly death. Two siblings affected with propionic acidemia were screened for putative mutations in PCCA and PCCB genes coding alpha and beta subunits of propionyl-coenzyme A (CoA) carboxylase, respectively. Both patients had a mild-severe form of propionic acidemia. The investigations using PCR, long-PCR, array comparative genomic hybridization (aCGH), and sequencing techniques showed a approximately 73kb deletion extending from intron 16 to intron 19 and an 18bp insertion at the distal end of the deletion in PCCA gene. The deletion so far is the largest gross change reported in the literature for the PCCA gene.
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PMID:Array comparative genomic hybridization (aCGH) reveals the largest novel deletion in PCCA found in a Saudi family with propionic acidemia. 1879 Jul 21

Maple syrup urine disease (MSUD) is a rare inborn error of metabolism, caused by a deficiency in activity of the branched chain alpha-keto acid dehydrogenase impairing the degradation of the branched-chain amino acids (leucine, isoleucine and valine). Classic MSUD usually manifests in the neonatal period with poor feeding, vomiting, lethargy, muscular hypertonicity, seizure, coma and death. Thirteen cases of classic MSUD were diagnosed from 1997-2007 at the Queen Sirikit National Institute of Child Health. All cases presented in the neonatal period. The onset of symptoms ranged from 3 to 20 days (median 8 days). The time taken to make the diagnosis ranged from 18 to 356 days (median 55 days). The diagnosis was accomplished by clinical diagnosis and confirmed by detecting abnormal levels of amino acids in the blood and organic acids in the urine. Clinical manifestations were non-specific such as poor suck, weak cry, drowsiness and seizures. Majority of cases were initially diagnosed as sepsis and/or meningitis. All patients had neurological sequelae and psychomotor retardation. This results show the need for increase awareness of metabolic disorder such as MSUD and the requirement for early detection and treatment to ensure a better outcome.
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PMID:Maple syrup urine disease in Thai infants. 1925 91

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder caused by a defect in glyoxylate metabolism attributable to low or absent activity of the liver-specific peroxisomal enzyme alanine/glyoxylate aminotransferase. This defect leads to enhanced conversion of glyoxylate to poorly soluble oxalate, which is then excreted into the urine. This process may lead to deposition of calcium oxalate crystals in many tissues as well as in the kidneys, resulting in nephrolithiasis, nephrocalcinosis, and/or renal failure. We present a 39-year-old patient with end-stage renal failure due to PH1, who was admitted with symptoms of feeling bloated, vomiting, diarrhea, and abdominal pain related to encapsulating peritoneal sclerosis (EPS). He had been treated with peritoneal dialysis for a total period of 5 years. EPS is a rare condition characterized by fibrosis and adhesions of the peritoneum to loops of the small intestine and has been described secondary to treatment with peritoneal dialysis. It also occurs in a variety of other clinical conditions such as autoimmune diseases and peritoneal and intra-abdominal malignancies. The calcium oxalate crystals found in the peritoneal fascia of this particular patient may suggest a causative relationship between crystal deposits and evolution to fibrosis and sclerosis of the peritoneum. The degree of impact of the peritoneal dialysis treatment itself on the development of EPS, however, is uncertain.
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PMID:Encapsulating peritoneal sclerosis in a patient with primary hyperoxaluria type 1: a case report. 2005 90

Glutaric aciduria type II, or multiple acyl-CoA dehydrogenase deficiency, is a rare metabolic disorder inherited in an autosomal recessive manner. The condition can be caused by mutations in at least 3 genes, including ETFA, ETFB, and ETFDH. When this potentially lethal disorder is known for its clinical and biochemical heterogeneity, mutation analysis will be an invaluable part of diagnosis. We here described a Chinese adolescent boy who enjoyed good health earlier and presented at the age of 14 years with severe vomiting. His condition deteriorated rapidly and he succumbed shortly after. With a travel history before presentation and the late age of onset, diagnosis was particularly difficult. Findings in perimortem biochemical investigations and postmortem autopsy were guiding but not diagnostic. The diagnosis of glutaric aciduria type II was finally confirmed by mutation analysis performed by direct sequencing on genomic DNA from peripheral blood, which identified 2 different unreported missense mutations, c.502G>T (p.V168F) and c.786A>G (p.Q262R), in ETFA. The father and the mother were found to be heterozygous for the 2 mutations in ETFA respectively. Subsequent molecular family screening also ruled out the disease in his elder sister, who had a history of convulsion and a suspicious plasma acylcarnitine profile, and freed her from life-long supplementation. The case showed that molecular autopsies should be part of routine postmortem examination of unexplained sudden death in all age groups and DNA-friendly samples should be routinely collected and archived. In the era of personalized medicine with the power of modern genetics, molecular diagnosis should be obtained for heterogeneous diseases with different genetic defects but sharing similar clinical and/or biochemical phenotypes.
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PMID:Role of postmortem genetic testing demonstrated in a case of glutaric aciduria type II. 2073 50


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