Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient is described with congenital hypotonia, lax joints, friable skin, hemorrhagic scars, high-arched palate, and borderline microcornea. Acid hydrolyzed whole skin collagen had a reduced hydroxylysine content of 0.5 residues per 1,000 as compared to 5.1 +/- 0.7 in control skin. Collagen lysyl hydroxylase in dialyzed subcellular fractions of cultured skin fibroblasts required L-ascorbate as a principal cofactor. Activity of this enzyme in cultured skin fibroblasts derived from this patient, his father, and mother were 17%, 66%, and 39% of control values, respectively. Collagen prolyl hydroxylase activity was normal. Pharmacologic amounts of oral vitamin C (4 gm/day) produced an increase and withdrawal resulted in abrupt diminution of urinary excretion of hydroxylysine. Over a two-year period the patient's wound healing and muscle strength improved and corneal diameter increased. Hydroxylysine content of the skin did not increase.
 ...
PMID:Inherited human collagen lysyl hydroxylase deficiency: ascorbic acid response. 41 88

We report four cases of congenital muscular dystrophy; all demonstrated hypotonia and multiple contractures at birth. Strength remained stationary or improved, but the tendency for contracture formation persisted. Brief small amplitude polyphasic potentials were recorded on electromyography, and muscle biopsy revealed extensive fat and/or collagen replacement, which was out of proportion to fiber necrosis or patient strength. The consistent clinical and pathologic features of these patients and others described in the literature justify considering this disorder to be a specific nosologic entity.
 ...
PMID:Congenital muscular dystrophy: case reports and reappraisal. 49 11

Two siblings suffered from Ehlers-Danlos syndrome characterized by skin fragility, joint laxity and dermal hyperelasticity. The association with microcornea and muscle hypotonia allowed the preliminary classification into type VI according to McKusick. Ultrastructure analysis of skin biopsies revealed poor integration of collagen fibrils into fibres; accordingly, the texture of the connective tissue appeared irregular. Lysyl hydroxylase activity of cultured skin fibroblasts was markedly reduced in the cells of the two patients. Preliminary studies revealed intermediate activity in the cells cultured from the skin of the parents. This finding suggested an autosomal recessive mode of inheritance. Unexpectedly and in contrast to the 3 cases reported in the literature, the hydroxylysine deficit in the patients' skin was, for reasons not yet understood, only mild. Therefore, amino acid analysis of skin is not adequate for the diagnosis of lysyl hydroxylase-deficient Ehlers-Danlos syndrome type VI.
 ...
PMID:Ehlers-Danlos syndrome in two siblings with deficient lysyl hydroxylase activity in cultured skin fibroblasts but only mild hydroxylysine deficit in skin. 118 96

Muscle biopsy and fibroblast culture of a floppy child with Ehlers-Danlos syndrome type IV were studied. Biochemical analysis of the tissue showed drastically reduced amount of collagen type III. Electron microscopic examination of muscle as well as of cultured fibroblasts showed grossly dilated and dominated the cytoplasm endoplasmic reticulum. Dilatation may result from storage of an abnormal collagen type III molecule. Our observations indicate that type III collagen deficiency may be present clinically as a congenital muscle hypotonia. Specific ultrastructural abnormalities of fibroblasts found in muscle biopsy can enable the proper diagnosis.
 ...
PMID:Type III collagen deficient EDS IV producing muscular hypotonia with abnormal muscle fibroblasts. 177 21

Between January and November 1988 20 a.-v. shunts for haemodialysis access were performed at the University Hospital of Zurich with the Omniflow, a prosthesis composed of sheep collagen and polyester mesh. The main reason to implant this vascular prosthesis was the failure of Cimino-shunts. In 9 cases a straight and in 11 cases a performed "u" shape graft was used. During the follow-up period of 3-11 months the following 6 complications were observed: 5 graft thrombosis (in 2 cases due to hypotonia, in other 2 cases due to wrong graft selection and in 1 case due to narrowed venous anastomosis), and one graft dysfunction due to a stenosis in the patients vein. In comparison to the vascular prostheses used earlier, the Omniflow graft is characterized by a high patency rate and an easy puncturing.
 ...
PMID:[Omniflow: a new vascular prosthesis for hemodialysis access]. 207 74

We studied two unrelated individuals with Ehlers-Danlos syndrome type VI, which is characterized by congenital hypotonia, lax joints, severe kyphoscoliosis, friable skin, and hemorrhagic hypotrophic scars. The diagnosis was confirmed by decreased hydroxylysine residues in dermal collagen and decreased collagen lysyl hydroxylase activities in their cultured skin fibroblasts. Despite the diminished hydroxylysine residues in dermal collagen from the probands, we found no differences in hydroxylysyl residues of collagen synthesized by fibroblasts in culture. When patient 1 was given oral sodium ascorbate (5 g/d) for 3 weeks, ascorbate concentrations increased two-fold in plasma and 300-fold in urine. Urinary excretion of hydroxylysine and hydroxyproline increased during ascorbate administration. After a 1-year interval, bleeding time, wound healing, and muscle strength improved. Ascorbate supplementation (50 micrograms/mL) to confluent fibroblasts cultured from the two patients and controls increased hydroxyprolyl and hydroxylysyl residues of fibroblasts four to seven and three to four-fold respectively. Total protein associated with the cell layer increased 14% to 32% without concomitant change in cellular DNA. Total soluble collagenous material recovered from culture media increased 61% to 103% with ascorbate supplementation. These studies demonstrate that ascorbate improves the clinical status of patients with impaired collagen lysyl hydroxylase activity by enhancing lysyl and prolyl hydroxylation and total collagen production.
 ...
PMID:Ascorbate regulation of collagen biosynthesis in Ehlers-Danlos syndrome, type VI. 311 May 40

Morphological study of peripheral nerves in two patients with globoid cell leucodystrophy (Krabbe's disease) demonstrates: 1degree segmentary demyelination; 2degrees marked loss of large (8-10 micra) myelinated fibres; 3degrees significant increase of the mean transverse fascicular area by proliferating collagen fibres; 4degrees electron-microscopic signs of remyelination with small onion-bulb formations. These findings can explain clinical features such as the disappearance of the deep tendon reflexes, the gradual transition of hypertonia into combined hypertonia-hypotonia and the concomitant slowing of nerve conduction velocity. The ultrastructural study reveals the presence of large and small inclusions which are either located within lysosomes or free in the cytoplasm of Schwann cells and fibroblasts. The inclusions are probably consequences of the disturbed metabolism of cerebrosides. Their appearance is sufficiently specific in order to allow a diagnosis of Krabbe's disease.
 ...
PMID:[Globoid cell leucodystrophy (Krabbe's disease). Peripheral nerve lesion (author's transl)]. 437 97

A case of an unusual congenital intramedullary tumor of the spinal cord is reported. A paraplegic 11-day-old boy with hypotonia and atrophy of the abdominal and lower-extremity muscles showed a complete myelographic block between T-5 and T-8. Surgical exploration disclosed an elongated tumor mass within the spinal cord, that blended with the surrounding nervous-system tissue. Light and electron microscopy showed that the tumor was composed of intermingled well differentiated astrocytes and fibroblasts. These two cell types often were surrounded by the same basal lamina. There were no intercellular junctions. Gliofibrils were abundant, and the interstitial spaces contained abundant collagen and reticulin fibers. There were no histological signs of malignancy. We conclude that this is a case of prenatally arising gliofibroma.
 ...
PMID:Prenatal intramedullary gliofibroma. A light and electron microscope study. 669 58

Congenital muscular dystrophies (CMDs), are heterogeneous autosomal recessive disorders. Their severe manifestations consist of early hypotonia and weakness, markedly delayed motor milestones and contractures, often associated with joint deformities. Histological changes seen in muscle biopsies consist of large variations in muscle fibre size, a few necrotic and regenerating fibres and a marked increase in endomysial collagen tissue. Diagnosis is based on clinical features and on morphological changes. In several CMD cases, we have demonstrated an absence of one of the components of the extracellular matrix around muscle fibres, the merosin M chain, now referred to as the alpha 2 chain of laminin-2 (ref.3). We localized this CMD locus to chromosome 6q2 by homozygosity mapping and linkage analysis. The laminin alpha 2 chain gene (LAMA2) maps to the same region on chromosome 6q22-23 (ref. 5). We therefore investigated LAMA2 for the presence of disease-causing mutations in laminin alpha 2 chain-deficient CMD families and now report splice site and nonsense mutations in two families leading presumably to a truncated laminin alpha 2 protein.
 ...
PMID:Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. 755 Mar 55

The type VI variant of the Ehlers-Danlos syndrome (EDS) is a recessively inherited connective-tissue disorder. The characteristic features of the variant are muscular hypotonia, kyphoscoliosis, ocular manifestations, joint hypermobility, skin fragility and hyperextensibility, and other signs of connective-tissue involvement. The biochemical defect in most but not all patients is a deficiency in lysyl hydroxylase activity. Lysyl hydroxylase is an enzyme that catalyzes the formation of hydroxylysine in collagens and other proteins with collagen-like amino acid sequences. We have recently reported an apparently homozygous large-duplication rearrangement in the gene for lysyl hydroxylase, leading to the type VI variant of EDS in two siblings. We now report an identical, apparently homozygous large duplication in an unrelated 49-year-old female originally analyzed by Sussman et al. Our simple-sequence-repeat-polymorphism analysis does not support uniparental isodisomy inheritance for either of the two duplications. Furthermore, we indicate in this study that the duplication in the lysyl hydroxylase gene is caused by an Alu-Alu recombination in both families. Cloning of the junction fragment of the duplication has allowed synthesis of appropriate primers for rapid screening for this rearrangement in other families with the type VI variant of EDS.
 ...
PMID:Alu-Alu recombination results in a duplication of seven exons in the lysyl hydroxylase gene in a patient with the type VI variant of Ehlers-Danlos syndrome. 797 51


1 2 3 4 Next >>