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)

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

In order to study the effect of long-term administration of co-trimoxazole on renal function, creatinine clearance rates were measured in 18 patients with neurogenic hypotonia of the bladder due to paraplegia, quadriplegia, hemiplegia and cerebrocervical injuries. The duration of the prophylactic treatment was between 60 and 80 days. The initial average creatinine clearance rate of this group was 99-0 ml/min and the final one was 110-7 ml/min (P = 0-15, n.s.). In addition, in seven cases the prophylaxis was extended to a period of 330 to 430 days. In this group the initial average creatinine clearance rate was 104-4 ml/min and the final one was 94-7 ml/min (P greater than 0-3, n.s.). It is concluded, therefore, that prolonged administration of co-trimoxazole to patients with creatinine clearance above 50 ml/min does not cause any marked deterioration in the renal function.
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PMID:Effect of long-term co-trimoxazole therapy on renal function. 119 10

The oculo-cerebral-renal syndrome of Lowe is an X-linked recessive disorder characterized by severe mental retardation, congenital cataracts, renal tubular dysfunction, growth retardation, hypotonia, glaucoma, and rickets. Recently, it has been found that serum concentrations of the muscle enzymes are elevated, providing evidence that there is primary muscle involvement in this disorder. The renal functional abnormalities that occur have also been further delineated. Renal tubular dysfunction presents within the first year of life, followed by a serum creatinine level that increases with age. Renal failure generally occurs in the fourth decade of life. We report two patients with Lowe's syndrome who presented with new onset of acute renal failure (ARF). Workup of their ARF established the diagnosis of acute tubular necrosis with evidence of rhabdomyolysis in one case. These patients were treated aggressively with dialysis and had subsequent recovery of renal function to their baseline state. We suggest that patients with Lowe's syndrome who present with an acute change in their renal function should be treated early with vigorous hydration therapy. If dialysis is indicated, it should be initiated. Furthermore, these patients should be promptly evaluated for evidence of rhabdomyolysis with alkalinization of the urine if possible.
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PMID:Acute tubular necrosis associated with Lowe's syndrome: possible role of rhabdomyolysis. 141 9

Myopathy may be associated with the syndrome of seroconversion in individuals infected by the human immunodeficiency virus (HIV) or may represent the initial symptom of AIDS. In 1990, 39-year old white, single homosexual who was admitted 1 month prior had experienced an episode of edema and pain in the left thigh that faded with the use of nonhormonal antiinflammatory drugs. 15 days later both forearms became enlarged accompanied by pain and erythema. Erythromycin and cefalexine were used without success. Intermittent fever started to appear before admission accompanied by dyspnea when straining. Examination showed tachypnea, oral candidiasis, and enlargement of both upper arms with pain and local erythema without articular involvement. Neurological examination revealed hypotonia and generalized hyperreflexia with intact muscle strength. Serology was positive for HIV, rheumatic activity tests were negative, and muscle biopsy indicated multifocal myonecrosis. Creatinine phosphokinase was 1019 IU (decrease to 44 IU after treatment), aldolase was 19 IU (decrease to 5.6 IU), and glutamic-pyruvic transminase was 50 IU (decrease to 22 IU). Radiography of the thorax indicated interstitial infiltration. Fiberoptic bronchoscopy indicated Pneumocystis carinii pneumonia. Sulfamethoxazole and trimetropim treatment cured the dyspnea and hypoxemia, but the enlargement of both arms progressed. Capillaroscopy indicated vasculitis that was treated without success with indomethacin (150 mg/day), for 7 days; prednisone (40-80 mg/day) for 10 days; and dexamethasone (280 mg/day) for 2 days. 6 days after methotrexate (50 mg/dose/week) treatment the fever disappeared and the enlargement in the extremities receded, but a lower dose of 7.5 mg caused the return of fever and edema in the right thigh. The myopathy remained asymptomatic for 5 months with a weekly dose of 15 mg of methotrexate.
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PMID:[AIDS and myopathy: report of a case and review of the literature]. 180 40

We studied two children who developed normally for the first 3-4 months of life and then displayed a failure-to-thrive syndrome, regression in psychomotor development, pronounced muscular hypotonia, and liver damage. At the age of about 1-2 years, optic atrophy and spastic parapareses were evident. One child died at the age of 2.5 years the other at an age of 4 years. Both children excreted 3-methylglutaconic acid, 0.1-0.4 mol/mol creatinine and 3-methylglutaric acid, 0.02-0.05 mol/mol creatinine. The excretion of 3-hydroxy-3-methylglutaric acid was not increased. One of the children was available for further biochemical studies. The activity of hydroxymethylglutaryl-CoA lyase (EC 4.1.3.4) was moderately reduced in leucocytes and fibroblasts. During a 21-h fast there was a normal formation of ketone bodies and we conclude that the cause of the syndrome is not a deficiency of hydroxymethylglutaryl-CoA lyase. Normal formation of 14CO2 from [1-14C]isovaleric acid and [2-14C]leucine in fibroblasts and leucocytes apparently excludes a deficiency of methylglutaconyl CoA-hydratase (EC 4.2.1.18).
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PMID:3-Methylglutaconic aciduria in two infants. 619 9

Bone density, anthropometric data, and markers of bone turnover were collected on 21 subjects diagnosed with Prader-Willi syndrome (PWS) and compared with 9 subjects with obesity of unknown cause. In addition, urinary N-telopeptide levels were obtained in all subjects. N-telopeptides are the peptide fragments of type I collagen, the major bone matrix material. During periods of active bone degradation or high bone turnover, high levels of N-telopeptides are excreted in the urine. However, no significant difference was detected in the urinary N-telopeptide levels when corrected for creatinine excretion (raw or transformed data) between our subjects with obesity or PWS and the observed effect size of the between-group difference was small. Although N-telopeptide levels were higher but not significantly different in the subjects with PWS compared with obese controls, the subjects with PWS had significantly decreased total bone and spine mineral density and total bone mineral content (all P < 0.001). No differences in N-telopeptide levels or bone mineral density were observed between subjects with PWS and chromosome 15q deletion or maternal disomy. Thus, decreased bone mineral density in subjects with PWS may relate to the lack of depositing bone mineral during growth when bones are becoming more dense (e.g., during adolescence), possibly because of decreased production of sex or growth hormones and/or long-standing hypotonia. It may not be caused by loss, or active degradation, of bone matrix measurable by the methods described in this study further supporting the possible need for hormone therapy during adolescence.
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PMID:Decreased bone mineral density in Prader-Willi syndrome: comparison with obese subjects. 1174 93

We report a rare case of an infant with congenital muscular dystrophy who presented at birth with marked generalized hypotonia and normal mental development. Creatinine phosphokinase (CPK) level was markedly raised; however no white matter abnormalities were detected by brain imaging techniques. Immunohistochemical staining for merosin (laminin alpha 2) was negative, thereby confirming merosin-deficient congenital muscular dystrophy.
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PMID:Merosin negative congenital muscular dystrophy: a short report. 1465 62

We generated a knockout mouse model for guanidinoacetate N-methyltransferase (GAMT) deficiency (MIM 601240), the first discovered human creatine deficiency syndrome, by gene targeting in embryonic stem cells. Disruption of the open reading frame of the murine GAMT gene in the first exon resulted in the elimination of 210 of the 237 amino acids present in mGAMT. The creation of an mGAMT null allele was verified at the genetic, RNA and protein levels. GAMT knockout mice have markedly increased guanidinoacetate (GAA) and reduced creatine and creatinine levels in brain, serum and urine, which are key findings in human GAMT patients. In vivo (31)P magnetic resonance spectroscopy showed high levels of PGAA and reduced levels of creatine phosphate in heart, skeletal muscle and brain. These biochemical alterations were comparable to those found in human GAMT patients and can be attributed to the very similar GAMT expression patterns found by us in human and mouse tissues. We provide evidence that GAMT deficiency in mice causes biochemical adaptations in brain and skeletal muscle. It is associated with increased neonatal mortality, muscular hypotonia, decreased male fertility and a non-leptin-mediated life-long reduction in body weight due to reduced body fat mass. Therefore, GAMT knockout mice are a valuable creatine deficiency model for studying the effects of high-energy phosphate depletion in brain, heart, skeletal muscle and other organs.
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PMID:Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency. 1502 68

Fumaric aciduria is a rare, autosomal recessive disorder caused by deficient activity of fumarate hydratase (FH). Common clinical features are hypotonia, failure to thrive, severe psychomotor retardation and seizures. Facial dysmorphism and brain malformations are frequent. Recently, some FH gene mutations have been associated with inherited cutaneous and uterine leiomyomas and papillary renal cell cancer. Our patient had a relatively mild phenotype, a previously not reported genotype and familial tumour predisposition. The mother and grandmother had uterine myomas. The paternal grandfather and his two brothers died from lung and laryngeal cancers. The pregnancy was complicated by bleeding and intrauterine growth retardation. Delivery was after 35 weeks, with normal Apgar score. The girl was hypotonic since birth. At age 2 months the parents noticed short apnoeic crises. She could sit at age 1.5 years, and walk with assistance at 4 years. At age 8 years highly increased excretion of fumaric acid was found twice (217 and 445 mmol/mol creatinine). Shortly before that the girl started to have leg and arm spasms. Grand mal seizures occurred twice. Facial dysmorphism included depressed nasal bridge, anteverted ears, hypertelorism and microcephaly. Speech was limited to few disyllables. She was atactic with spastic paraparesis. Brain MRI showed slight ventriculomegaly, white-matter atrophy and hypoplasia of corpus callosum. Activity of FH in fibroblasts was 1.9 nmol/min/mg protein (controls 40-80). Analysis of the FH gene revealed the maternally derived c.1029_1031delAGT mutation, resulting in Val deletion and substitution of Gln by His, and paternally derived c.976C > T mutation, resulting in substitution of Pro by Ser.
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PMID:Fumaric aciduria: mild phenotype in a 8-year-old girl with novel mutations. 1697 75

Guanidinoacetate methyltransferase (GAMT) deficiency is a rare disorder of creatine synthesis. We report a patient who presented at 10 months of age with hypotonia and global developmental delay. Subsequently, she developed seizures and choreoathetosis. Magnetic resonance imaging showed high signal bilaterally in the globus pallidus on T2-weighted images. Mitochondrial respiratory chain studies revealed low complex I activity (in muscle 0.052 nmol NADH oxidized per min per unit citrate synthase, controls 0.166 +/- 0.047; in fibroblasts 0.080 nmol NADH oxidized per min per unit citrate synthase, controls 0.197 +/- 0.034). The true diagnosis was suspected at 21 months of age because of persistent low plasma and urine creatinine concentrations. GAMT activity was undetectable in fibroblasts and compound heterozygous mutations were found in the GAMT gene (c.327G>A and c.522G>A). The patient was treated with creatine, dietary arginine restriction and ornithine supplements. Her movement disorder and seizures resolved but she still has severe cognitive impairment and no expressive language. The occurrence of secondary respiratory chain abnormalities in GAMT deficiency may lead to misdiagnosis, particularly as the clinical and radiological features resemble those seen in mitochondrial encephalopathies. It is important to establish the correct diagnosis because specific treatment is available.
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PMID:Guanidinoacetate methyltransferase deficiency masquerading as a mitochondrial encephalopathy. 1717 76


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