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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Functional methionine synthase deficiency is generally characterized by homocystinuria and hypomethioninemia in the absence of methylmalonic aciduria. Patients are divided into two classes, cblE and cblG, on the basis of complementation analysis. Presentation has usually been in the first 2 years of life, but one patient came to medical attention at age 21 years with symptoms initially diagnosed as multiple sclerosis. Common findings among 11 patients (4 with cblE and 7 with cblG) have included megaloblastic anemia (all patients) and various neurological deficits including developmental retardation (10 patients), cerebral atrophy (8 patients), hypotonia (7 patients), EEG abnormalities (6 patients), and nystagmus (5 patients). Hypertonia, seizures, blindness, and ataxia were less frequent. All patients have responded to therapy with cobalamin with resolution of anemia and biochemical abnormalities; neurological deficits resolved more slowly and in some cases incompletely. Hydroxycobalamin has been more effective than cyanocobalamin. Fibroblasts from patients with cblE (5 patients) and cblG (6 patients) all showed decreased intracellular levels of methylcobalamin (MeCbl) and decreased incorporation of label from 5-methyltetrahydrofolate into macromolecules, suggesting decreased activity of the MeCbl-dependent enzyme methionine synthase. Methionine synthase specific activity in extracts of all cblE fibroblasts was normal or near-normal under standard reducing conditions; synthase specific activity in extracts of 5 cblG patients was low but was high in a 6th patient measured in another laboratory. Thus, there is heterogeneity among patients with functional methionine synthase deficiency both in clinical presentation and in the results of biochemical studies of cultured cells.
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PMID:Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity. 268 21

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

Cobalamin C (cblC) defects result in decreased activity of both methylmalonyl-CoA mutase and N5-methyltetrahydrofolate:homocysteine methyltransferase (methionine synthase), with subsequent methylmalonic acid-uria and homocystinuria. Patients typically show failure to thrive, developmental delay and megaloblastic anaemia. Vitamin B12 therapy has been beneficial in some cases. We report a now 4-year-old Hispanic girl with cblC disease documented by complementation analysis, with progressive neurological deterioration and worsening head MRI changes while on intramuscular hydroxocobalamin begun at age 3 weeks. Oral carnitine and folic acid were added at age 1 year. Blood levels of methylmalonic acid were reduced to treatment ranges. In the absence of acute metabolic crises, she developed microcephaly, progressive hypotonia and decreased interactiveness. Funduscopic examination was normal at age 13 months. At age 19 months, she developed nystagmus, and darkly pigmented fundi and sclerotic retinal vessels were observed on examination. Her neonatal head MRI was normal. By age 1 year, the MRI showed diffuse white-matter loss with secondary third and lateral ventricle enlargement, a thin corpus callosum, and normal basal ganglia. At age 15 months, progression of the white-matter loss, as well as hyperintense globi pallidi, were present. Interval progression of both grey- and white-matter loss was seen at age 27 months. We therefore caution that progressive neurological deterioration and head MRI abnormalities may still occur in cblC disease, despite early initiation of hydroxocobalamin therapy and improvement in toxic metabolite concentrations in physiological fluids.
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PMID:Progressive neurological deterioration and MRI changes in cblC methylmalonic acidaemia treated with hydroxocobalamin. 1039 92

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

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

Epileptic seizures during infancy have a wide variety of clinical presentations and the outcome differs according to the etiology. Among the benign and rare causes of infantile seizures, Vitamin B12 deficiency has been encountered. Common symptoms of Vitamin B12 deficiency in infants include megaloblastic anemia, feeding difficulties, developmental delay, microcephaly, failure to thrive, hypotonia, lethargy, irritability, involuntary movements, seizures and cerebral atrophy. Involuntary movements and seizures may rarely be the initial symptoms of Vitamin B12 deficiency. Involuntary movements have also been reported to appear after initiation of Vitamin B12 supplementation in isolated cases, whereas, no such information exits for seizures. In this paper, three infants with Vitamin B12 deficiency associated with motor and mental retardation are reported because of long-lasting focal/multifocal epileptic seizures following the initiation of intramuscular Vitamin B12 treatment. Antiepileptics were introduced in addition to Vitamin B12. Seizures disappeared within a few days or weeks; electroencephalographic findings were normalized in a few months. No relapses occurred during the follow-up period.
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PMID:Seizures during treatment of Vitamin B12 deficiency. 1855 Mar 91

We report the case of a 7 month-old girl that presented with acute anemia, generalized muscular hypotonia and failure to thrive. Laboratory evaluation revealed cobalamin deficiency, due to a vegan diet of the mother. The clinical triad of an acquired floppy baby syndrome with megaloblastic anemia and failure to thrive is pathognomic for infantile cobalamin deficiency. Neurological abnormalities are often irreversible and may be associated with delayed myelinization in the MRI. A normal cobalamin level in maternal serum and absence of anemia do not exclude subclinical deficiency. If cobalamin deficiency is suspected, e.g. in pregnant women on vegan diet, urinary methylmalonic acid excretion and plasma homocysteine levels should be determined and cobalamin substitution should be started at an early stage to avoid potentially irreversible damage of the fetus.
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PMID:[Floppy baby with macrocytic anemia and vegan mother]. 1829 83

In developed countries, the vitamin B12 deficiency usually occurs in children exclusively breast-fed, whose mothers are vegetarians, causing low stores of vitamin B12. Symptoms of vitamin B12 deficiency appear during the second trimester of life and include failure to thrive, lethargy, hypotonia, and arrest or regression of developmental skills. A megaloblastic anemia can be present. One half of the infants exhibit abnormal movements before the start of treatment with intramuscular cobalamin, which disappear 1 or 2 days after. More rarely, movement disorders appear a few days after treatment, whereas neurological symptoms are improving. These abnormal movements can last for 2 to 6 weeks. If not treated, vitamin B12 deficiency can cause lasting neurodisability. Therefore, efforts should be directed to preventing deficiency in pregnant and breast-feeding women on vegan diets and their infants by giving them vitamin B12 supplements. When preventive supplementation has failed, one should recognize and treat quickly an infant presenting with failure to thrive and delayed development.
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PMID:Neurological consequences of vitamin B12 deficiency and its treatment. 1870 98


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