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)

Three neonatal patients, one girl and two boys, presented with infantile Pompe's disease. A generalized hypotonia with decreased tendon reflexes and heart failure due to hypertrophic cardiomyopathy dominated the clinical picture in all three; these symptoms are uniformly and characteristically present. This autosomal recessive glycogen storage disease is caused by a deficiency of lysosomal alpha-glucosidase. The diagnosis, suspected on the basis of the characteristic clinical picture and the results of simple laboratory tests, is made by measurement of the enzymatic activity or DNA analysis. Most patients die in their first year of life, no treatment being available.
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PMID:[Three hypotonic neonates with hypertrophic cardiomyopathy: Pompe's disease]. 975 27

A case report is presented in which a 4-year-old male is diagnosed with hypertrophic cardiomyopathy, respiratory distress, muscle hypotonia, and psychomotor retardation. Electron microscopic study of skeletal muscle biopsy revealed pathologic changes typical of congenital nemaline myopathy, and biochemical analysis revealed a disorder of mitochondrial fatty acid oxidation. Therefore a previously undescribed combination of a structural and metabolic myopathy is reported.
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PMID:Nemaline myopathy and cardiomyopathy. 1032 85

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

Noonan syndrome is one of the most common of genetic syndromes and manifests at birth, yet it is usually diagnosed during childhood. Although prenatal diagnosis of Noonan syndrome is usually not possible, in a few cases the ultrasonographic findings suggested the diagnosis in utero. Reported sonographic clues include septated cystic hygroma, hydrothorax, polyhydramnios, and cardiac defects, such as pulmonic stenosis and hypertrophic cardiomyopathy. During a 6-year period, 46,224 live-born infants were delivered at the Chaim Sheba Medical Center. Seven newborn infants and four fetuses were found to have Noonan syndrome. One fetus showed transient nuchal translucency of 4 mm and bilateral neck cysts at the 13th gestational week. Both findings resolved spontaneously by the 18th gestational week, but during the third trimester this fetus developed hydrothorax, skin edema, and polyhydramnios. In the three other fetuses, first- and second-trimester ultrasonographic findings were normal, and the diagnosis of Noonan syndrome was suggested only during the third trimester. All three fetuses had polyhydramnios and skin edema. A cardiac malformation, hydrothorax, and a large head were present in one fetus. Sonographic facial findings were investigated. In all four fetuses posteriorly angulated, apparently low-set ears and depressed nasal bridge were identified. Wide nasal base was seen in two fetuses. In two fetuses, persistent opening of the fetal mouth was interpreted as fetal hypotonia. One fetus developed progressive postnatal hypertrophic cardiomyopathy and in one case, pulmonic stenosis became apparent at age 6 months. This small series suggests that Noonan syndrome has an evolving phenotype during in utero and postnatal life. Amelioration of early nuchal region findings and late onset of the more "typical" ultrasonographic changes may limit early prenatal detectability.
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PMID:Noonan syndrome: a cryptic condition in early gestation. 1081 48

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

Respiratory chain complex I deficiencies represent a genetically heterogeneous group of diseases resulting from mutations in either mitochondrial or nuclear DNA. Combination of denaturing high performance liquid chromatography and sequence analysis allowed us to show that a 4-bp deletion in intron 2 (IVS2+5_+8delGTAA) of the NDUFV2 gene (encoding NADH dehydrogenase ubiquinone flavoprotein 2) causes complex I deficiency and early onset hypertrophic cardiomyopathy with trunk hypotonia in three affected sibs of a consanguineous family. The homozygous mutation altering the consensus splice-donor site of exon 2 resulted in 70% decreased NDUFV2 protein and complex I deficiency. While mutation in a number of genes encoding complex I subunits essentially result in neurological symptoms, this first mutation in NDUFV2 is strikingly associated with cardiomyopathy, as previously observed in the unique case of NDFUS2 mutations.
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PMID:Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy. 1275 3

Glycogen storage disease type II (GSD-II), also known as Pompe disease, is a rare autosomial recessive disease due to deficiency of lysosomal acid alpha-glucosidase (GAA). The infantile-onset form is the most severe, and most patients present with hypotonia and cardiomyopathy in early infancy. We report on a typical case of Pompe disease in a patient who died at 8 months of age due to aspiration pneumonia and hypertrophic cardiomyopathy. Genetic studies showed deficient GAA activity and mutation of the GAA gene with Gly615Arg (exon 13, G1845A). On autopsy, glycogen had markedly accumulated in the liver, myocardium and skeletal muscle. The neurons of the anterior horn of the spinal cord and medulla were also involved, but the cortex was spared. These neurological-histologic findings may explain the clinical features of poor motor function, decreased deep tendon reflexes and lack of mental retardation.
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PMID:Infantile-onset glycogen storage disease type II (Pompe disease): report of a case with genetic diagnosis and pathological findings. 1536 15

Congenital disorders of glycosylation (CDG) represent a newly delineated group of inherited multisystem disorders characterized by defective glycoprotein biosynthesis. In the present study we report and discuss the clinical and neuropathological findings in a newborn with CDG type Ia (CDG-Ia). The patient presented mild dysmorphic facial features, inverted nipples, progressive generalized edema, hypertrophic cardiomyopathy, hepatosplenomegaly, muscular hypotonia and had severe hypoalbuminemia. Deficiency of phosphomannomutase (PMM)-2 activity was detected. Molecular analysis showed V231M/T237R mutations of the PMM2 gene. Muscular biopsy, disclosed myopathic alterations with myofibrillar disarray by electron microscopy. The patient died at 1 month of age of circulatory and respiratory failure. Autopsy showed liver fibrosis and renal abnormalities. Neuropathological abnormalities were mainly confined to the cerebellum. Histological and immunocytochemical examination of cerebellar tissue showed partial atrophy of cerebellar folia with severe loss of Purkinje cells, granular cell depletion and various morphological changes in the remaining Purkinje cells and their dendritic arborization. Autopsy findings confirm the complexity of the CDG-Ia syndrome, and indicate that CDG-Ia is a distinct disease entity, which can be differentiated from other neurological disorders and other types of CDG, not only clinically, but also based on unique pathological findings. The data proved useful in determining the underlying disease process associated with a defective N-glycosylation pathway.
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PMID:Congenital disorder of glycosylation type Ia: a clinicopathological report of a newborn infant with cerebellar pathology. 1571 16

3-Methylglutaconic aciduria is the biochemical marker of several inherited metabolic diseases. Four types of 3-methylglutaconic aciduria can be distinguished. In the type I form, accumulation of 3-methylglutaconate is due to deficient activity of 3-methylglutaconyl-CoA hydratase, an enzyme of the leucine degradation pathway. In the other forms, 3-methylglutaconic acid is not derived from leucine but is of unidentified origin, possibly derived from other metabolic pathways, such as mevalonate metabolism. We report five patients, all presenting a severe early-onset phenotype characterized by 3-methylglutaconic aciduria, hypertrophic cardiomyopathy, cataract, hypotonia/developmental delay, lactic acidosis, and normal 3-methylglutaconyl-CoA hydratase activity. This peculiar phenotype, for which a primary mitochondrial disorder is hypothesized, identifies a novel subtype of 3-methylglutaconic aciduria.
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PMID:Hypertrophic cardiomyopathy, cataract, developmental delay, lactic acidosis: a novel subtype of 3-methylglutaconic aciduria. 1673 96

We present clinical and laboratory data from 14 cases with an isolated deficiency of the mitochondrial ATP synthase (7-30% of control) caused by nuclear genetic defects. A quantitative decrease of the ATP synthase complex was documented by Blue-Native electrophoresis and Western blotting and was supported by the diminished activity of oligomycin/aurovertin-sensitive ATP hydrolysis in fibroblasts (10 cases), muscle (6 of 7 cases), and liver (one case). All patients had neonatal onset and elevated plasma lactate levels. In 12 patients investigated 3-methyl-glutaconic aciduria was detected. Seven patients died, mostly within the first weeks of life and surviving patients showed psychomotor and various degrees of mental retardation. Eleven patients had hypertrophic cardiomyopathy; other clinical signs included hypotonia, hepatomegaly, facial dysmorphism and microcephaly. This phenotype markedly differs from the severe central nervous system changes of ATP synthase disorders caused by mitochondrial DNA mutations of the ATP6 gene presenting mostly as NARP and MILS.
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PMID:Deficiency of mitochondrial ATP synthase of nuclear genetic origin. 1705 6


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