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)

Several childhood multisystem disorders with prominent ophthalmological manifestations have been ascribed to the malfunction of the peroxisome, a subcellular organelle. The peroxisomal disorders have been divided into three groups: 1) those that result from defective biogenesis of the peroxisome (Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum's disease); 2) those that result from multiple enzyme deficiencies (rhizomelic chondrodysplasia punctata); and 3) those that result from a single enzyme deficiency (X-linked adrenoleukodystrophy, primary hyperoxaluria type 1). Zellweger syndrome, the most lethal of the three peroxisomal biogenesis disorders, causes infantile hypotonia, seizures, and death within the first year. Ophthalmic manifestations include corneal opacification, cataract, glaucoma, pigmentary retinopathy and optic atrophy. Neonatal adrenoleukodystrophy and infantile Refsum's disease appear to be genetically distinct, but clinically, biochemically, and pathologically similar to Zellweger syndrome, although milder. Rhizomelic chondrodysplasia punctata, a peroxisomal disorder which results from at least two peroxisomal enzyme deficiencies, presents at birth with skeletal abnormalities and patients rarely survive past one year of age. The most prominent ocular manifestation consists of bilateral cataracts. X-linked (childhood) adrenoleukodystrophy, results from a deficiency of a single peroxisomal enzyme, presents in the latter part of the first decade with behavioral, cognitive and visual deterioration. The vision loss results from demyelination of the entire visual pathway, but the outer retina is spared. Primary hyperoxaluria type 1 manifests parafoveal subretinal pigment proliferation. Classical Refsum's disease may also be a peroxisomal disorder, but definitive evidence is lacking. Early identification of these disorders, which may depend on recognizing the ophthalmological findings, is critical for prenatal diagnosis, treatment, and genetic counselling.
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PMID:The peroxisome and the eye. 171 72

A term newborn male with severe hypotonia and contractures was found to have dense bilateral cataracts. He died at age 3 days of respiratory failure. Amino acidopathies and disorders of peroxisome function were excluded, and results of serologic studies and placental histopathology, specifically seeking evidence of intrauterine infection, were normal. Autopsy showed changes in the skeletal muscles consistent with congenital muscular dystrophy and a small focal anomaly of the cerebral cortex. These findings either represent a new syndrome or raise further questions about broadening the spectrum of known congenital muscular dystrophy syndromes with associated eye and brain anomalies.
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PMID:Lethal congenital muscular dystrophy with cataracts and a minor brain anomaly: new entity or variant of Walker-Warburg syndrome? 186 58

A 23-year-old male with clinically diagnosed Lowe syndrome had bilateral cataracts, glaucoma, pendulous nystagmus, severe mental and growth retardation, hypotonia, areflexia, joints hyperextensibility, proteinuria, aminoaciduria, and metabolic acidosis. There was also severe epileptic activity (Lennox-Gastaut syndrome). The neuropathological examination revealed a marked cerebellar atrophy and central chromatolysis in the cerebral cortex. These observations do not confirm the hypothesis of dysmyelination as formulated in previous studies. The reported case rather suggests the existence of a dynamic process starting as a still-undefined metabolic abnormality that, in turn, causes various and inconsistent lesions at the microscopic level.
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PMID:Lowe syndrome: clinical and neuropathological studies of an adult case. 207 36

We report a sibship of two brothers and one sister with the osteoporosis-pseudoglioma syndrome and congenital heart disease. They presented in infancy with visual impairment and psychomotor retardation. Major features included bilateral cataracts, generalised osteopenia, severe platyspondyly, borderline mental retardation, muscular hypotonia, joint laxity, and ventricular septal defect. Parental consanguinity and affected sibs of both sexes strongly suggested autosomal recessive inheritance. Analysis of the present and previously reported cases showed a wide range of interfamilial variability which may point to the existence of multiple allelism or genetic heterogeneity in this syndrome.
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PMID:Osteoporosis-pseudoglioma syndrome with congenital heart disease: a new association. 335 89

We report a familial case of Lowe's syndrome with histological and ultrastructural examination of the renal biopsy. The patient was an eleven years old boy with operated congenital bilateral cataracts, mental and psychomotor retardation, hyperexcitability, muscular hypotonia, proteinuria, generalised aminoaciduria, proximal tubular acidosis and reduced glomerular filtrate. The renal biopsy showed, in addition to the alterations in the glomerular corpuscle (mesangial proliferation), proximal tubules (atrophy, dilatation, hyalinous or calcerous cylindres and mitochondrial abnormalities) and interstitium (fibrosis, lymphocytic infiltrate), large number of cortical microcysts, many of with corresponded to Bowman's cystic capsules with small glomeruloid projections.
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PMID:[Cortical renal microcysts in Lowe's syndrome]. 405 42

Thirty-three patients (20 female and 13 male patients aged 13 to 52 years) with myotonic dystrophy (MyD) were studied. Ophthalmologic examination included tonography, electroretinography (ERG), and fluorescein angiography. Thirty patients had bilateral cataracts of the subcapsular type, two patients had aphakia in both eyes, and one patient had clear lenses. Hypotonia (intraocular pressure, less than or equal to 10 mm Hg) was a common finding in 19 of 66 eyes. The mean IOP was 11.8 mm Hg for the whole series and the mean outflow facility was c = 0.34 cu mm/min. Focal signs of retinouveal affection were present in nine patients. Clinically, they appeared as acquired lesions affecting the retina, pigment epithelium, and choroid. One patient was found to have an outburnt panuveitis. The ERG was normal in 11 patients, subnormal in five patients, and isoelectric in four patients. An extinguished ERG did not correlate to clinical findings of known hereditary retinal or choroidal dystrophies. The ophthalmologic findings may be explained by a primary defect related to the cell membrane.
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PMID:Ocular findings in myotonic dystrophy. 712 55

The most commonly reported manifestations of 16q deletions are severe growth and developmental disorders and anomalies of the craniofacial, visceral, and musculoskeletal systems. We reviewed the findings of patients reported with 16q- syndrome and compared them to our patient, a 4 1/2-year-old boy with a deletion of 16q23.1. Findings include psychomotor retardation, hypotonia, high forehead, hypertelorism, upslanting palpebral fissures, low-set abnormally modeled ears, and talipes equinovarus. Anomalies present in our patient not reported in others with 16q- syndrome include bilateral cataracts, iris coloboma, and autistic-like behavior. It is of note that a locus for autosomal dominant congenital cataract, known as Marner cataract, was mapped previously to 16q22. Because our patient has bilateral cataracts and a unilateral iris coloboma, it seems likely that a gene involved in ocular development is located within 16q23.1. Our patient's deletion may also include the gene involved in Marner cataract and may further assist in the isolation of this gene.
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PMID:Cytogenetic and clinical findings in a patient with a deletion of 16q23.1: first report of bilateral cataracts and a 16q deletion. 940 69

Mutations in the inositol 5-phosphatase OCRL are responsible for Lowe syndrome, an X-linked disorder characterized by bilateral cataracts, mental retardation, neonatal hypotonia, and renal Fanconi syndrome, and for Dent disease, another X-linked condition characterized by kidney reabsorption defects. We have previously described an interaction of OCRL with the endocytic adaptor APPL1 that links OCRL to protein networks involved in the disease phenotype. Here, we provide new evidence showing that among the interactions which target OCRL to membranes of the endocytic pathway, binding to APPL1 is the only one abolished by all known disease-causing missense mutations in the ASH-RhoGAP domains of the protein. Furthermore, we demonstrate that APPL1 and rab5 independently contribute to recruit OCRL to enlarged endosomes induced by the expression of constitutively active Rab5. Thus, binding to APPL1 helps localize OCRL at specific cellular sites, and disruption of this interaction may play a role in disease.
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PMID:All known patient mutations in the ASH-RhoGAP domains of OCRL affect targeting and APPL1 binding. 1830 81

Dynamin 2 (DNM2)-related dominant centronuclear myopathy is usually a mild disorder, but more severe variants have been associated with mutations affecting the pleckstrin homology (PH) domain of the protein, mainly implicated in different forms of Charcot-Marie-Tooth Disease (CMT). Whilst DNM2-related CMT may feature non-neurological findings including cataracts, this has not been reported in DNM2-related centronuclear myopathy. We report a girl presenting from birth with hypotonia, respiratory and feeding difficulties. Motor development was delayed and at 9years she lost the ability to walk. She had ptosis, external ophthalmoplegia and bilateral cataracts. Muscle biopsy showed increase in central nuclei with type 1 hypotrophy and fibrosis. DNM2 screening revealed a novel heterozygous substitution (c.1862T>C; p.Leu621Pro) affecting the PH domain of the protein. Her further course was progressive and at 14years she died from respiratory failure. Our findings expand the phenotypical spectrum associated with DNM2 mutations and provide a new clinical indicator for involvement of this gene in patients with centronuclear myopathy.
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PMID:Centronuclear myopathy with cataracts due to a novel dynamin 2 (DNM2) mutation. 1993 20

Congenital disorders of glycosylation (CDG) are caused by enzymatic defects of the formation or processing of lipid-linked oligosaccharides and glycoproteins. Since the majority of proteins is glycosylated, a defect in a singular CDG enzyme leads to a multisytemic disease with secondary malfunction of thousands of proteins. CDG-Ij (DPAGT1-CDG) is caused by a defect of the human DPAGT1 (UDP-GlcNAc: Dolichol Phosphate N-Acetylglucosamine-1-Phosphotransferase), catalyzing the first step of N-linked glycosylation. So far the clinical phenotype of only one CDG-Ij patient has been described. The patient showed severe muscular hypotonia, intractable seizures, developmental delay, mental retardation, microcephaly and exotropia. Molecular studies of this patient revealed the heterozygous mutation c.660A>G (Y170C; paternal) in combination with an uncharacterized splicing defect (maternal). Two further mutations, c.890A>T (I297F) and c.162-8G>A as a splicing defect were detected when analyzing DPAGT1 in two affected siblings of a second family. We report two new patients with the novel homozygous mutation, c.341C>G (A114 G), causing a severe clinical phenotype, characterized by hyperexcitability, intractable seizures, bilateral cataracts, progressive microcephaly and muscular hypotonia. Both our patients died within their first year of life. With the discovery of this novel mutation and a detailed clinical description we extend the clinical features of CDG-Ij in order to improve early detection of this disease.
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PMID:Congenital disorder of glycosylation type Ij (CDG-Ij, DPAGT1-CDG): extending the clinical and molecular spectrum of a rare disease. 2230 30


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