Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The clinical and morphologic findings of three patients with metabolic acidosis, methylmalonic aciduria, and homocystinuria are presented. The clinical evolution of the patients was similar and was characterized in the first weeks of life by failure to thrive, hypotonia, and lethargy associated with pancytopenia and hepatic dysfunction, eventually progressing to severe respiratory insufficiency and renal failure consistent with a hemolytic-uremic syndrome. The patients died at 40, 45, and 75 days of age. Biochemical analyses and complementation studies revealed a congenital anomaly of vitamin B12 metabolism (cobalamin C disease). Postmortem morphologic findings in all three cases were dominated by a thrombotic microangiopathy of the kidneys and lungs, diffuse hepatic steatosis, and megaloblastic changes in the bone marrow. A severe gastritis with striking cystic dysplastic mucosal changes and total absence of parietal and chief cells was a consistent finding in all three cases, the rest of the gastrointestinal tract appearing essentially normal. Cobalamin C disease is an intracellular defect of cobalamin metabolism with possible recessive inheritance that can result in multiorgan failure early in life, with a thrombotic microangiopathy and unusual changes in the gastric mucosa.
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PMID:A congenital anomaly of vitamin B12 metabolism: a study of three cases. 156 46

The case of a 15-month-old, strictly breast-fed infant whose mother had been following a vegetarian diet for ten years is reported. The infant had severe megaloblastic anemia with an arrest in growth, hypotonia, and failure of psychomotor development. The very low levels of vitamin B12 in the infant's serum and mother's milk confirmed the diagnosis. Management of such cases consists in administration of vitamin B12 supplements, with a blood transfusion if needed. Other concomitant deficiencies should be looked for. The outcome is rapidly favorable. The patient reported here is now four years of age and has normal statural growth and psychomotor development.
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PMID:[Severe megaloblastic anemia in child breast fed by a vegetarian mother]. 844 42

The cases of three infants, two Saudi and one Bahraini, with methylenetetrahydrofolate reductase (MTHFR) deficiency are reported. They presented in the neonatal period with lethargy, poor feeding, hypotonia, and frequent apneas. Tandem mass spectrometry (MS/MS) of a blood spot indicated very low methionine level and of urine revealed high homocysteine. The diagnosis was confirmed by demonstrating severe deficiency of MTHFR in the cultured skin fibroblast. All patients were treated with folinic acid, vitamin B12, betaine, and methionine, with good initial response to the therapy. In two patients, the diagnosis was late and their disease was severe, resulting in neurological crippling. However, in the third patient, who was diagnosed and treated early, the current neurological status is normal. In her case, at 1 month of age, the brain FDG PET scan documented very faint cerebral and cerebellar cortical activities. After 5 months of intensive therapy, that included 200-600 mg/kg per day methionine, she had a dramatic clinical and biochemical recovery as well as a parallel improvement in FDG PET. Brain MR spectroscopy indicated normal neuronal glial and myelin markers for her age. We conclude that the functional changes confirmed by the FDG PET study were better correlated with the clinical course of the patient and adequately monitored the response to therapy. This disease warrants early detection through neonatal screening program, since the beneficial effect of early administration of adequate therapy with combined use of betaine and a high dose of methionine is rewarding and may be the treatment of choice for MTHFR deficiency.
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PMID:Clinical, fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography of the brain, MR spectroscopy, and therapeutic attempts in methylenetetrahydrofolate reductase deficiency. 1041 24

Methylmalonic acidemia (MMA) is an inborn error of organic acid metabolism that occurs in infancy with hypotonia, vomiting, dehydration, lethargy and failure to thrive and is biochemically characterized by metabolic ketoacidosis, hyperammonemia and sometimes hyperglycinemia. It results from deficiency of methylmalonyl-CoA mutase activity due to a defect in the mutase apoenzyme or to deficient function of one of the enzymes required for metabolism of its cofactor vitamin B12. Tubulointerstitial nephritis with progressive impairment of renal function is one of the most frequent long-term complications. We describe a case of a 17-year-old girl with methylmalonic acidemia unresponsive to vitamin B12 therapy. The clinical symptoms appeared at 4 months of life. She progressed into end stage renal disease and in January 1996 she started on hemodialytic treatment. In November 1996 we performed a kidney transplant. At present, urinary excretion of methylmalonic acid is normal and the renal function of the transplanted kidney is normal without any rejection episodes. We think that a kidney transplant could be a good therapeutic choice for the metabolic alterations in MMA with end stage renal disease. Indeed it would seem that the small methylmalonyl-CoA mutase activity present in the transplanted kidney could be sufficient to ensure normal metabolism of organic acids. Otherwise, the therapeutic goal can be achieved with a protein-restricted diet.
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PMID:Kidney transplantation in a girl with methylmalonic acidemia and end stage renal failure. 1168 86

Anew case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. A 28-day-old boy presented with failure to thrive, hypotonia, pancytopenia, and features of HUS (microangiopathic hemolytic anemia, thrombocytopenia, and renal failure). The possibility of the diagnosis of an underlying vitamin B12 disorder was prompted by evidence of megaloblastic changes on the peripheral smear and by finding in the literature a suggested association of neonatal HUS with this cobalamin-related metabolic disorder. Amino acid analysis showed elevated homocysteine levels in the plasma and increased levels of both homocysteine and methyl malonic acid in the urine. Diagnosis of cobalamin C disease was confirmed by complementation studies using skin fibroblasts. Therapy included parenteral hydroxocobalamin, carnitine, and leucovorin calcium (folinic acid). Cobalamin C disease should be considered in the diagnosis of patients presenting with HUS in infancy who have unexplained megaloblastosis, pancytopenia, neurologic impairment, and failure to thrive. Early diagnosis and institution of therapy may be effective in improving survival and quality of life.
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PMID:Cobalamin C disease presenting as hemolytic-uremic syndrome in the neonatal period. 1197 7

Vegan diet in lactating women can induce vitamin B12 deficiency for their children with risk of an impaired neurological development. A 9.5-month-old girl presented with impaired growth and severe hypotonia. She had a macrocytic anemia secondary to vitamin B12 deficiency. MRI showed cerebral atrophy. She was exclusively breastfed. Her mother was also vitamin B12 deficient, secondary to a vegan diet. She had a macrocytic anemia when discharged from the maternity. Vegan diet is a totally inadequate regimen for pregnant and lactating women, especially for their children. Prevention is based on screening, information and vitamin supplementation.
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PMID:[Breastfeeding and vegan diet]. 1620 6

Vitamin B12 deficiency can cause serious developmental regression, hypotonia and cerebral atrophy in infants. We report a 6-month-old infant, with insidious developmental regression and brain atrophy showed by CT scan, secondarily to vitamin B12 deficiency. His mother was a strict vegetarian and the patient was exclusively breastfed. The clinical symptoms and the brain CT were normalized after vitamin B12 administration.
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PMID:Vitamin B12 deficiency in infancy as a cause of developmental regression. 1631 May 94

A 1-year-old boy with weight loss, decreased activity, and psychomotor regression is presented. He was subjected to an extremely detailed evaluation, including electroencephalography (EEG) and magnetic resonance imaging (MRI), until a simple hemogram in our center revealed that he had macrocytic anemia with megaloblastic changes in the bone marrow. His history revealed that he had been exclusively breast-fed by his vegetarian mother. Further investigations showed low serum vitamin B12 concentration, methylmalonic aciduria, and homocysteinemia, indicating that the macrocytic anemia was due to vitamin B12 deficiency. This boy represents a case of macrocytic anemia and hypotonia owing to vitamin B12 deficiency that developed because of exclusive breast-feeding by a vegetarian mother.
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PMID:Answer to hypotonia: a simple hemogram. 1641 68

In developing countries, a deficiency of cobalamine and folate contributes significantly to megaloblastic anaemia. Neurological observations in infants and young children with megaloblastic anaemia have included hypotonia, developmental regression, tremors and other abnormal movements. Following therapy with vitamin B12, coarse tremors occurred in six of 51 patients (12%) with megaloblastic anaemia. The tremors, which were noticed initially in the hands and feet, gradually became generalised and disappeared during sleep. They subsided within 5-11 days. Thirteen of 25 (52%) patients developed thrombocytosis between day 3 and week 5 of follow-up. In one child, the platelet count increased to >1300 x 10(9)/L. The importance of recognising these clinical findings during treatment of megaloblastic anaemia is emphasised.
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PMID:Tremors and thrombocytosis during treatment of megaloblastic anaemia. 1670 27


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