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)

Two infants with lethargy, vomiting, convulsions, coma and marked metabolic acidosis were found to have very high concentrations of methylmalonic acid in their serum and urine. In vitro studies of fibroblasts demonstrated that the infants had different variants of methylmalonic acidemia.Vitamin B(12) was given in two different forms at 1 month of age and at 12 months of age. Each trial continued for 4 months but neither infant showed a clinical or biochemical response.In both infants hyperglycinemia, neutropenia and thrombocytopenia developed during acute metabolic crises only. Hypoglycemia was found in patient 2. Hyperammonemia was severe in patient 2 during acute crises but never appeared in patient 1. When clinically well, both infants continued to excrete abnormal amounts of methylmalonic acid in the urine and both had persistent compensated metabolic acidosis.Marked hyperuricemia developed in patient 1 at 18 months of age and led to progressive renal failure. Allopurinol therapy was necessary to keep the uric acid concentration within the normal range. Renal function returned to normal, as indicated by a marked increase in the renal clearance of creatinine and uric acid.Patient 1 is physically and mentally retarded, and has moderate hypotonia, hepatomegaly and persistent vomiting. Patient 2 has developed normally.The urine concentrations of methylmalonic acid in the four parents were normal.
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PMID:Methylmalonic acidemia: 6 years' clinical experience with two variants unresponsive to vitamin B12 therapy. 3 17

Congenital methylmalonic aciduria (MMA) is a metabolic disorder inherited by an autosomal recessive trait. The metabolic block is located in the catabolic pathway of propionyl-CoA to succinyl-CoA. Biochemically, four enzymatic defects have been recognized, i.e.: 1. Methylmalonyl-CoA racemase. 2. Methylmalonyl-CoA mutase apoenzyme. 3. Synthesis of desoxyadenosyl-cobalamine. 4. Disturbance at an earlier level of cobalamine metabolism which causes defective synthesis of both vitamin B12-coenzymes. These four enzymatic defects express themselves in three ways: non-vitamin B12-dependent MMA (defects 1 and 2); vitamin B12-dependent MMA (defect 3); MMA associated with homocystinuria (defect 4). The various forms of MMA cannot be distinguished clinically from one another. The disorder manifests itself during the first few days to weeks of life. Principal symptoms and signs are: anorexia, vomiting, muscular hypotonia and metabolic acidosis. The diagnosis is established by determination of methylmalonic acid in plasma, cerebrospinal fluid and urine, as well as by assay of enzyme activities in leukocytes, liver tissue or cultured fibroblasts (from biopsied skin). A prenatal diagnosis is feasible by the examination of cultured amnion cells, amniotic fluid and maternal urine. Therapy of non vitamin B12-dependent MMA calls for reduction of protein intake, particularly that of precursors of methylmalonic acid, such as methionine, threonine, isoleucine and valine. The treatment of vitamin B12-dependent forms is accomplished by i.m. injection of high doses of vitamin B12. No definite statement can be made as yet with regard to long-term prognosis and normalcy of mental development in treated children.
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PMID:[Methylmalonic aciduria. Classification, diagnosis and therapy (author's transl)]. 31 93

A case of methylmalonic acidemia with intermittend homocystinuria is described. Special attention is given to the early symptoms of this inborn error of metabolism, like lethargy, muscular hypotony, poor feeding, ketoacidosis, and recurrent vomiting. Furthermore, the necessary diagnostic steps, the pertinent differential diagnosis (septicemia, duodenal stenosis, other inborn errors of metabolism), and the possible treatment are discussed.
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PMID:[A case of cobalamin-dependent methylmalonic acidemia. Biochemical aspects, diagnosis and possible treatment (author's transl)]. 65 92

A 3-month-old male infant had two episodes of fever, projectile vomiting, dehydration, generalized fine tremors and gross metabloic ketoacidosis. Methylmalonic acid was found in high concentration in both serum and urine, although the concentration of serum vitamin B12 was normal. A therapeutic trial of vitamin B12, administered parenterally, reduced greatly the methylmalonic aciduria. The patient has since been given vitamin B12 supplements continuously, initially 1 mg intramuscularly every other day, then 15 mg/d orally, and the protein in his diet was subsequently restricted. The most effected control of the methylmalonic aciduria was achieved with the combined regimen of oral vitamin therapy and dietary protein restriction. His physical and intellectual development have progressed normally and he has survived several acute respiratory tract infections without recurrence of metabolic acidosis.
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PMID:Methylmalonic acidemia controlled with oral administration of vitamin B12. 95 84

The reported case was a female infant aged 7 months with severe ketoacidosis associated with vomiting, dehydration and cardiorespiratory disturbances at the time of exacerbation of the disease. The analysis of urinary organic acids by the GC-MS method revealed methylmalonic aciduria. After placing the infant on a low-protein diet (1.5 g of protein per 1 kg of body weight) and initially vitamin B12 parenterally a striking clinical improvement with evident progress in psychomotor development of the child was achieved.
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PMID:A case of vitamin B12--independent methylmalonic aciduria. 184 19

Although propionic acidemia and methylmalonic acidemia, two disorders of branched-chain amino acid metabolism often complicated by chronic anorexia and vomiting, are not usually treated with parenteral nutrition for fear of amino acid overload and exacerbation of biochemical derangements, we gave long-term parenteral nutrition to two critically ill patients with these disorders. Health and growth were restored, and there was minimal production of abnormal metabolites. The dramatic clinical and biochemical improvement of these patients bolsters the concept that most of the toxic metabolites produced in these diseases are not related to the administered load of nutrient precursors, but rather to endogenous turnover of amino acids, particularly during a chronic catabolic state. Suppression of catabolism can produce striking biochemical and clinical improvement. With appropriate monitoring, parenteral nutrition can be used safely in the management of patients with these disorders.
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PMID:Parenteral nutrition in propionic and methylmalonic acidemia. 211 11

A male infant with methyl-B12 deficiency (cblE) presented at age 6 weeks with lethargy, staring spells, and vomiting. He later became hypotonic and unresponsive to stimuli and required intubation and ventilation. He had homocystinuria and hypomethioninemia with megaloblastic anemia but normal serum folate and vitamin B12 concentrations. No methylmalonic aciduria was detected. Fibroblasts, cultured from the patient, were unable to grow in medium in which homocysteine replaced methionine and incorporated abnormally small amounts of [14C]-methyl-tetrahydrofolate but normal amounts of [14C]-propionate into protein. Methyl-B12 content of fibroblasts was low, while the adenosyl-B12 content was normal. Methionine synthase activity was decreased when the assay was performed under both optimal and suboptimal reducing conditions, suggesting heterogeneity in the cblE disease. The patient responded dramatically to hydroxocobalamin treatment. Homocystinuria disappeared after 10 days of therapy, and methionine was normalized after 3 weeks. Psychometric testing at age 15 months showed a developmental age of 9 months.
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PMID:Vitamin B12 responsive homocystinuria and megaloblastic anemia: heterogeneity in methylcobalamin deficiency. 381 89

A 7-month-old boy presented with vomiting and failure to thrive associated with proteinuria, methylmalonic aciduria and macrocytosis, but without anaemia. Plasma vitamin B12 levels were normal by a radio-dilution method. He was treated as an inborn error of metabolism with intramuscular cyanocobalamin and a low protein diet. However when treatment was withdrawn he remained well for 11 months before relapsing with vomiting and weight loss. Re-investigation again showed methylmalonic aciduria, but the haemoglobin was low and plasma vitamin B12 levels by a specific method showed them to be reduced. Studies of vitamin B12 absorption showed the picture of selective malabsorption. He was started on regular cyanocobalamin injections.
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PMID:Selective vitamin B12 malabsorption without anaemia but with profound failure to thrive. 400 74

Methylmalonic acidemia is an inherited metabolic disorder thus far found in children and characterized by the excessive excretion of methylmalonate in the urine. Typically these children exhibit vomiting, lethargy, ketoacidosis, and failure to grow. Many of the patients are mentally retarded and die early in life. Two variants of this disease are known. In one, the administration of vitamin B(12) will reverse or prevent these clinical findings, whereas in a second variant vitamin B(12) therapy is of no value. This paper presents the first enzymatic evidence (obtained with cell-free liver extracts) that bears on two important aspects of the disease. It has been found that methylmalonylCoA carbonylmutase activity is essentially absent in the livers of patients suffering from one variant (vitamin B(12)-unresponsive) of the disease. Secondly, it has been found that the livers of patients with the second variant (vitamin B(12)-responsive) of the disease show normal enzymatic behavior in the presence of the coenzyme form of vitamin B(12), but are identical to the vitamin B(12)-unresponsive variant in the absence of the added coenzyme. Thus the enzyme studies fully support the clinical observations that two types of this disease exist.
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PMID:Congenital methylmalonic acidemia: enzymatic evidence for two forms of the disease. 525 62

Methylmalonic acidemia is a recessively inherited inborn error of metabolism presenting with metabolic acidosis, vomiting, lethargy, anorexia, and hypotonia. The disease may either begin in the neonatal period with acute, life-threatening episodes, or manifest itself with a milder clinical course and a more favorable outcome depending on the location and the severity of enzyme block. Enzymatic abnormalities, clinical features, diagnostic approach with regard to differential diagnosis and the possible treatment are discussed. Genetic counseling and prenatal diagnosis are also stressed.
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PMID:[Methylmalonic acidemia: classification, diagnosis and therapy]. 636 67


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