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)

Severe neonatal centronuclear myopathy is inherited as an X-linked condition characterized by primary asphyxia, extreme muscular hypotonia and absent spontaneous movements. We report seven cases from three families to point out the importance of diagnosis with regard to prognosis, outcome and genetic counselling. In hypotonic diseases, analysis of cerebrospinal fluid, electromyography, nerve conduction velocity creatine kinase and a skin biopsy for fibroblast cultures for metabolic investigations are usually carried out. Needle muscle biopsy is an additional valuable investigation to establish diagnosis. In all our patients we found an increased number of centrally located nuclei with perinuclear halos confirming the diagnosis of centronuclear myopathy. The diagnosis of this disorder will become of greater importance as soon as carrier detection and prenatal diagnosis by DNA-technology are routinely available.
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PMID:Severe neonatal asphyxia due to X-linked centronuclear myopathy. 227 10

We report on five girls (including monozygotic twins) with a newly recognized disease comprising severe neurologic disturbances, variable hepatomegaly, abnormal subcutaneous fat distribution and skeletal anomalies. The neurologic picture was characterized by moderate to severe psychomotor retardation, alternating internal strabismus , hypotonia, hyporeflexia and ataxia. Biochemical investigations showed a number of abnormalities such as tubular proteinuria, slightly increased serum transaminases, hypoalbuminemia, hypo-beta-lipoproteinemia and decreased serum thyroxine-binding globulin. Moreover there was retinitis pigmentosa, cerebellar hypotrophy and electrophysiologic evidence for a peripheral neuropathy. However, histologic examination of a nerve biopsy in one of the patients failed to show myelin abnormalities. On the other hand, abnormal lamellar inclusions were found in the lysosomes of some Schwann cells and of liver tissue as well. Additional investigations in four patients revealed a deficiency of sialic acid, galactose and N-acetylglucosamine of plasma glycoproteins. Enzymatic analysis of serum suggested a deficiency of an N-acetyl-glucosaminyltransferase. Remarkably, the (healthy) fathers but not the mothers presented the same carbohydrate deficiencies of plasma glycoproteins albeit to a much lesser degree. The mode of hereditary transmission of this disease remains unclear; the possibility of X-linked inheritance is under investigation.
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PMID:[A not-previously described hereditary neurological disease with a deficiency of sialic acid, galactose and N-acetylglucosamine of plasma glycoproteins]. 260 46

At the eve of its mapping, the pre-molecular picture of the FG syndrome is heavily biased towards the severe end of the phenotypic spectrum because present knowledge is largely based on propositi. It is an X-linked, incompletely recessive, complexly pleiotropic syndrome with considerably variable expressivity. Though a true multiple congenital anomalies/mental retardation (MCA/MR) syndrome, severe malformations are uncommon and involve mostly the anus (60%) and non-colonic GI defects (33%), hypospadias (25%), cleft palate (6%), rarely a congenital heart defect. The complex CNS dysfunctions of congenital hypotonia and all of its sequelae, MR, and occasional seizures, must be attributed to a developmental CNS defect which is rarely demonstrated at pre-mortem, and which is known to involve agenesis of the corpus callosum in some 25% of appropriately studied patients (mostly propositi). Thus, the diagnosis is largely made on a specific constellation of minor anomalies and mild malformations in a hypotonic boy with severe constipation and a very characteristic facial appearance and behavioral phenotype. In about 1/3 of cases, carrier manifestations may be detected physically. New hemizygote manifestations seen in this review of 5 new patients include abnormal eruption of teeth, diastasis between upper central incisors, apparent gynecomastia, cleft lip, and nasolacrimal and helicine fistulae. Only a half hundred or so FG syndrome patients are known, but we suspect the syndrome is much more common than realized, and because of the unfortunate recurrence risk potential, deserves careful consideration in every appropriate case. RFLP mapping studies are urged in order to aid diagnosis of "mild" cases, and prenatal and carrier detection.
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PMID:FG syndrome update 1988: note of 5 new patients and bibliography. 305 62

Four male infants from three sibships in an extended family were noted to have hypotonia, areflexia, and congenital joint contractures. The findings of electromyography and muscle histology were consistent with infantile spinal muscular atrophy (SMA). Pedigree analysis suggests that this disorder represents an X-linked, recessive form of SMA. Findings in similar kindreds may explain the previously reported increased male-female ratio in infantile SMA.
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PMID:X-linked infantile spinal muscular atrophy. 334 27

Lowe (oculocerebrorenal) syndrome (LS) is an X-linked disorder characterized by congenital cataracts, generalized hypotonia, mental retardation, and renal Fanconi syndrome. The basic defect remains unknown, but the possibility that fibroblasts express reduced sulfation of glycosaminoglycans has been studied in several laboratories. A mechanism involving overproduction of an enzyme (nucleotide pyrophosphatase) active against adenosine 3'-phosphate, 5'-phosphosulfate (PAPS) has been postulated. Decreased synthesis of normally sulfated glycosaminoglycans was also reported. We measured the synthesis of proteoglycans and glycosaminoglycans by incorporation of [3H]glucosamine and Na2(35)SO4 into cultured fibroblasts from four LS patients and related it directly to the synthesis in six normal fibroblast cultures. We found that the rate of synthesis varied greatly among the normal cultures (cv, 30%), but not significantly between LS and the normal. The LS fibroblasts' ability to sulfate glycosaminoglycans was assayed as the amount of 3H-glycosaminoglycan eluting at low ionic strength on anion exchange chromatography, the amount of non-sulfated disaccharide present in chondroitinase digests of labeled proteoglycans, and the ratio of 35S to 3H incorporation into proteoglycans. Each parameter suggested that the LS cells were synthesizing normally sulfated glycosaminoglycans (e.g. % delta Di-0S, 21 +/- 6 in normal; 27 +/- 6 in LS). The cells' ability to sulfate glycosaminoglycans was tested under conditions of markedly stimulated glycosaminoglycan synthesis, by treating the cultures with a beta-D-xyloside. LS and normal cells responded to the treatment by elevating the rate of synthesis of normally sulfated glycosaminoglycans (3.5-6-fold in normal, 3-7-fold in LS). Nucleotide pyrophosphatase activities were found to be elevated in each of our four LS cell strains as in the previous studies, excluding genetic heterogeneity as an explanation for our findings. We conclude that LS fibroblasts do not express defects in sulfation of glycosaminoglycans or in synthesis of proteoglycans.
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PMID:Proteoglycan synthesis in normal and Lowe syndrome fibroblasts. 357 Dec 27

We describe an X-linked disorder of the CNS, characterized by onset, in infancy, of hypotonia, ataxia, sensorineural deafness, developmental delay, esotropias, and optic atrophy, and by a progressive course leading to death in childhood. Pathologically, neuron loss and gliosis of the dentate nucleus and inferior olive are conspicuous; involvement of the cerebellar cortex is less prominent. In the proband, the red nucleus, dorsal motor nucleus of the vagus, and central auditory pathways were severely affected. The mother of the proband, now 33, has self-limited episodes of ataxia, and cerebellar atrophy for which no other cause is apparent. The unique heredity, pathology, and clinical picture distinguish this entity from previously described inherited or metabolic ataxias.
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PMID:Infantile X-linked ataxia and deafness: a new clinicopathologic entity? 361 54

Nephrogenic diabetes insipidus usually presents with polyuria, polydipsia, fever, vomiting, dehydration and failure to thrive. However, in infancy polyuria may be absent because of dehydration and reduced glomerular filtration rate. In 2 cases the main presenting feature was hypotonia, with marked head lag. Family studies confirmed the X-linked mode of inheritance of the disease; in case 1 the disease appeared to have arisen as a new mutation in the mother, and in case 2 the carrier status was traced back to the great-grandmother. Pitfalls in the diagnosis and detection of the carriers are discussed. Treatment with thiazide diuretics and prostaglandin synthesis inhibitors is effective in reducing urine volumes and polydipsia. The early detection of the disease and adequate management may prevent such complications as megacystis, mega-ureter and hydronephrosis, with resulting renal failure. Mental and physical retardation may also be avoided.
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PMID:Nephrogenic diabetes insipidus presenting with infantile hypotonia. A report of 2 cases. 373 62

Prenatal onset and rapidly fatal course of centronuclear myopathy are described in four male newborns including two brothers. Diagnosis was established by muscle biopsy within the first week of life in two and at autopsy in the two other patients: Central nuclei, central aggregation of oxydative enzyme activity in the majority of muscle fibers and type 1 fibre hypotrophy were demonstrated. Prenatal manifestation included polyhydramnios, reduced fetal movements and breech presentation. All four newborns developed respiratory insufficiency requiring artificial ventilation immediately after birth. Severe muscular weakness and hypotonia as well as hardly elicitable grasping, deep tendon reflexes and Moro response were noticed. Additional findings included high arched palate, joint contractures, thin ribs, lung hypoplasia, abundant skin and cryptorchidism. In two families, the pedigree contains other affected males, suggesting X-linked inheritance. Seven female carriers were clinically healthy and one of them showed normal muscle histology. Fourteen previously published neonatal cases of centronuclear myopathy are reviewed and compared with our findings. This severe perinatal form of centronuclear myopathy has to be considered in male fetuses and newborns with polyhydramnios and respiratory failure due to muscular weakness or in infants who died of unexplained postnatal asphyxia. Diagnosis should be established by muscle biopsy.
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PMID:Severe neonatal centronuclear (myotubular) myopathy: an X-linked recessive disorder. 379 8

The X-linked FG syndrome is characterised by mental retardation, congenital hypotonia and constipation (which may both be severe), structural anal anomalies and relative macrocephaly in some, and an unusual and characteristic facial appearance. We describe 7 males from 4 families. One had anal stenosis. Two of the mothers and one sister show probable carrier manifestations. The features of the FG syndrome are individually non-specific. We emphasize that the characteristic combination of features is needed to avoid overdiagnosis.
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PMID:The FG syndrome: 7 new cases. 401 79

The oculocerebrorenal syndrome (OCRS), Lowe's syndrome, is an X-linked, recessive disease characterized by mental retardation, congenital corneal abnormalities and cataracts, growth failure, rickets, osseous abnormalities, renal dysfunction with periodic acidosis, hypotonia, and areflexia. Ultrastructural studies of skin biopsy specimens in three individuals with the disorder (aged 17, 9, and 8 years) revealed cytoplasmic, membrane-bound, electron-lucent vacuoles and some electron-dense membranous inclusion bodies in fibroblasts and Schwann cells, as well as axonal degeneration and vascular changes. Computed tomographic scans evidenced brain atrophy. Urinary excretion of glycosaminoglycans (GAG) was four to five times greater than in normal controls. The predominant urinary GAG was a low-sulfated chondroitin-4-sulfate; chondroitin-6-sulfate and heparan sulfate excretion levels were normal. A tenfold increase in urinary GAG excretion was found in one patient with oculocerebrorenal syndrome during periods of behavioral agitation. These findings suggest that the clinical stigmata of oculocerebrorenal syndrome may be related to a defect in GAG metabolism.
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PMID:Ultrastructural, neurological, and glycosaminoglycan abnormalities in lowe's syndrome. 608 20


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