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)

Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is a disorder of fatty acid beta oxidation that reportedly has high rates of morbidity and mortality. We describe the outcome of a 5-year-old girl with VLCAD deficiency who was first seen at 5 months of age with severe hypertrophic cardiomyopathy, hepatomegaly, encephalopathy, and hypotonia. Biochemical studies indicated VLCAD deficiency caused by a stable yet inactive enzyme. Molecular genetic analysis of her VLCAD gene revealed a T1372C (F458L) missense mutation and a 1668 ACAG 1669 splice site mutation. After initial treatment with intravenous glucose and carnitine, the patient has thrived on a low-fat diet supplemented with medium-chain triglyceride oil and carnitine and avoidance of fasting. Her ventricular hypertrophy resolved significantly over 1 year, and cognitively, she is in the superior range for age. Clinical recognition of VLCAD deficiency is important because it is one of the few directly treatable causes of cardiomyopathy in children.
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PMID:Reversal of severe hypertrophic cardiomyopathy and excellent neuropsychologic outcome in very-long-chain acyl-coenzyme A dehydrogenase deficiency. 970 14

Malonyl coenzyme A (CoA) decarboxylase (E.C.4. 1.1.9) catalyzes the conversion of malonyl CoA to acetyl CoA. The metabolic role of malonyl CoA decarboxylase has not been fully defined, but deficiency of the enzyme has been associated with mild mental retardation, seizures, hypotonia, cardiomyopathy, vomiting, hypoglycemia, metabolic acidosis, and malonic aciduria. Here we report the isolation and sequencing of the human gene encoding malonyl CoA decarboxylase, and the identification of a mutation causing malonyl CoA decarboxylase deficiency. Human malonyl CoA decarboxylase cDNA sequences were identified by homology to the goose gene, and the intron/exon boundaries were determined by direct sequencing of a PAC clone containing the entire human gene. The 1479 basepair human cDNA is 70 percent identical to the goose sequence, and the intron/exon boundaries are completely conserved between the two species. The genetic mutation underlying malonyl CoA decarboxylase deficiency was determined in a patient with clinical features of this defect, malonic aciduria, and markedly reduced malonyl CoA decarboxylase activity.
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PMID:Cloning and mutational analysis of human malonyl-coenzyme A decarboxylase. 986 65

D-2-Hydroxyglutaric aciduria has been observed in patients with extremely variable clinical symptoms, creating doubt about the existence of a disease entity related to the biochemical finding. An international survey of patients with D-2-hydroxyglutaric aciduria was initiated to solve this issue. The clinical history, neuroimaging, and biochemical findings of 17 patients were studied. Ten of the patients had a severe early-infantile-onset encephalopathy characterized by epilepsy, hypotonia, cerebral visual failure, and little development. Five of these patients had a cardiomyopathy. In neuroimaging, all patients had a mild ventriculomegaly, often enlarged frontal subarachnoid spaces and subdural effusions, and always signs of delayed cerebral maturation. In all patients who underwent neuroimaging before 6 months, subependymal cysts over the head or corpus of the caudate nucleus were noted. Seven patients had a much milder and variable clinical picture, most often characterized by mental retardation, hypotonia, and macrocephaly, but sometimes no related clinical problems. Neuroimaging findings in 3 patients variably showed delayed cerebral maturation, ventriculomegaly, or subependymal cysts. Biochemical findings included elevations of D-2-hydroxyglutaric acid in urine, plasma, and cerebrospinal fluid in both groups. Cerebrospinal fluid gamma-aminobutyric acid was elevated in almost all patients investigated. Urinary citric acid cycle intermediates were variably elevated. The conclusion of the study is that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with at least two phenotypes.
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PMID:D-2-Hydroxyglutaric aciduria: biochemical marker or clinical disease entity? 989 84

Current dietary management of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD; long-chain-(S)-3-hydroxyacyl-CoA:NAD+ oxido-reductase, EC 1.1.1.211) deficiency (LCHADD) is based on avoiding fasting, and minimizing energy production from long-chain fatty acids. We report the effects of various dietary manipulations on plasma and urinary laboratory values in a child with LCHADD. In our patient, a diet restricted to 9% of total energy from long-chain fatty acids and administration of 1.5 g medium-chain triglyceride oil per kg body weight normalized plasma acylcarnitine and lactate levels, but dicarboxylic acid excretion remained approximately ten times normal. Plasma docosahexaenoic acid (DHA, 22:6n-3) was consistently low over a 2-year period; DHA deficiency may be related to the development of pigmentary retinopathy seen in this patient population. We also conducted a survey of metabolic physicians who treat children with LCHADD to determine current dietary interventions employed and the effects of these interventions on symptoms of this disease. Survey results indicate that a diet low in long-chain fatty acids, supplemented with medium-chain triclyceride oil, decreased the incidence of hypoketotic hypoglycaemia, and improved hypotonia, hepatomegaly, cardiomyopathy, and lactic acidosis. However, dietary treatment did not appear to effect peripheral neuropathy, pigmentary retinopathy or myoglobinuria.
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PMID:Dietary management of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). A case report and survey. 1023 7

It has recently been recognized that D-2-hydroxyglutaric aciduria is a distinct neurometabolic disorder with a severe and a mild phenotype. Whereas the clinical and neuroimaging findings of the severe phenotype were homogeneous among the patients, the findings in the mild phenotype were much more variable, leaving the clinical picture poorly defined. We were able to collect the clinical, biochemical and neuroimaging data on an additional 8 patients with D-2-hydroxyglutaric aciduria, 4 with the severe and 4 with the mild phenotype. With the new information, it becomes clear that the mild phenotype shares the essential characteristics of the severe phenotype. The most frequent findings, regardless of the clinical phenotype, are epilepsy, hypotonia and psychomotor retardation. Additional findings, mainly occurring in the severe phenotype, are episodic vomiting, cardiomyopathy, inspiratory stridor and apnoeas. The most consistent MRI finding is enlargement of the lateral ventricles, occipital more than frontal. Regardless of the clinical phenotype, early MRI shows in addition subependymal cysts and signs of delayed cerebral maturation. Later MRI may reveal multifocal cerebral white-matter abnormalities. Two patients had vascular abnormalities, but it is as yet unclear whether these are related to D-2-hydroxyglutaric aciduria or are incidental findings.
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PMID:D-2-hydroxyglutaric aciduria: further clinical delineation. 1040 77

We have reviewed published reports on patients with segmental aneusomy for chromosome 1p36 to help geneticists and other health professionals in the recognition of this emerging chromosomal syndrome. Terminal deletions of the short arm of chromosome 1 are associated with hypotonia and developmental delay (usually severe), growth abnormalities (growth retardation, microcephaly, obesity), and craniofacial dysmorphism with a large anterior fontanelle, prominent forehead, deep set eyes, flat nasal bridge and midface hypoplasia, ear asymmetry, a pointed chin, and orofacial clefting. Minor cardiac malformations, cardiomyopathy, seizures, and ventricular dilatation are the more common additional findings. Sensorineural hearing loss and variable ophthalmological anomalies have also been frequently observed. Although the deletions can be detected by high resolution cytogenetic studies, confirmation by fluorescence in situ hybridisation is required in most cases. The majority of deletions are maternally derived. Molecular characterisation of 1p36 deletions has been undertaken in several cases, and it is likely that this condition is a contiguous gene deletion syndrome.
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PMID:Monosomy 1p36. 1050 20

Carbohydrate-deficient glycoprotein syndrome (CDGS) is a newly delineated group of inherited multisystemic disorders associated with abnormal glycosylation of a number of serum glycoproteins. Several types have been described on the basis of clinical presentation and biochemical changes of the glycosylation of serum transferrin and attributed to different enzymatic defects; their clinical presentations are fully different and a clinical heterogeneity is observed within a same type of CDGS. Patients with CDGS type la usually present with neurologic (hypotonia, strabismus and cerebellar hypoplasia) and cutaneous (inverted nipples, abnormal distribution of adipose tissue) abnormalities, together with multivisceral involvement (digestive, hepatic, cardiac, renal). However, neurologic and cutaneous symptoms may be absent, so that CDGS must be looked for in case of unexplained organ failure such as isolated liver insufficiency, cardiomyopathy, pericarditis, tubulopathy, nephrotic syndrome, vascular accident or retinitis pigmentosa. Patients with CDGS type Ib present with liver disease, enteropathy and hypoglycemia without neurologic involvement. These patients are successfully treated with oral mannose administration emphasizing the importance of making the diagnosis. Patients with CDGS type Ic present with mild psychomotor retardation and seizures. Patients with CDGS type II have psychomotor retardation association with severe gastrointestinal disorder, dysmorphic features and abnormal electroretinogram. Other types (III, IV) are less clearly defined and the clinical presentation includes convulsive encephalopathy. Biological abnormalities such as mild hepatic cytolysis, hematologic and hormonal abnormalities are consistently observed in CDGS type I, as well as renal hyperechogeneity, leading one to look for this syndrome when they are associated. Until now, only four enzymatic deficiencies have been identified (types Ia, Ib, Ic, II).
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PMID:[Carbohydrate-deficient blood glycoprotein syndrome]. 1070 Oct 64

We describe an 8-day-old baby girl presenting a fatal infantile form of hypertrophic obstructive cardiomyopathy, associated with an A8296G mutation in the mitochondrial tRNA(Lys) gene. She was born from a healthy unrelated couple, and was the first infant of dizygotic twins. Soon after birth, she was noted to have tachypnea and generalized hypotonia. She had high levels of lactate and pyruvate, and was diagnosed as having hypertrophic cardiomyopathy using echocardiography. She died by cardiac failure. Mitochondrial DNA analysis was performed by sequencing after PCR-subcloning methods, and the percentage of mutation was measured using PCR-RFLP methods. In various tissues obtained at autopsy, analysis showed a heteroplasmic population of A8296G mutation in the mitochondrial tRNA(Lys) gene in all the tissues examined. Maternal inheritance was demonstrated in the family members. Our data demonstrated that an A8296G mutation in the mitochondrial tRNA(Lys) gene showed clinical heterogeneity from a milder form previously reported as mitochondrial diabetes mellitus, to a more severe form as hypertrophic obstructive cardiomyopathy, according to the spatial distribution of this mutation. Hum Mutat 15:382, 2000.
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PMID:Fatal hypertrophic cardiomyopathy associated with an A8296G mutation in the mitochondrial tRNA(Lys) gene. 1073 88

An infant presented with congenital weakness, hypotonia, arthrogryposis, atrial tachycardia, and a left intra-abdominal neuroblastoma. Muscle biopsy revealed marked excess of muscle spindles with atrophy of extrafusal fibers. The patient expired at age 14 months from progressive cardiorespiratory failure. Postmortem examination demonstrated muscle-spindle excess in other muscles, along with hypertrophic obstructive cardiomyopathy and organomegaly. Muscle spindle excess has previously been reported in two patients with Noonan syndrome and progressive hypertrophic cardiomyopathy. Muscle spindle excess with hypertrophic cardiomyopathy, organomegaly, and, possibly, congenital neuroblastoma suggests a syndromic association and may represent an unusual form of congenital myopathy.
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PMID:Myopathy with muscle spindle excess: A new congenital neuromuscular syndrome? 1115 Sep 80

Mitochondrial disorders are multisystem diseases with very heterogeneous clinical manifestations. Common cardiac features include cardiomyopathy and conduction defects. We report a five-year-old boy who presented with signs of congestive cardiac failure and was diagnosed to have dilated cardiomyopathy. Six months later, he developed progressively worsening ataxia, hypotonia, other cerebellar signs, hearing loss, severe sensory peripheral neuropathy and lactic acidosis. Electronmicroscopy of skeletal muscle biopsy was consistent with mitochondrial myopathy.
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PMID:Mitochondrial myopathy presenting as ataxia with dilated cardiomyopathy. 1137 Apr 43


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