Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new syndrome of autosomal recessive spastic ataxia has been isolated in the Charlevoix-Saguenay region of Quebec. This syndrome is remarkably homogeneous and includes: spasticity, dysarthria, distal muscle wasting, foot deformities, truncal ataxia, absence of sensory evoked potentials in the lower limbs, retinal striation reminiscent of early Leber's atrophy and the frequent presence (57%) of a prolapse of the mitral valve. Biochemically, many cases show impaired pyruvate oxidation, others have hyperbilirubinaemia and some have low serum beta-lipoproteins and HDL apoproteins. These features are similar to those found in typical Friedreich's ataxia.
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PMID:Autosomal recessive spastic ataxia of Charlevoix-Saguenay. 64 99

Spinocerebellar ataxial 1 (SCA1) is the locus name of autosomal dominant olivopontocerebellar atrophy (OPCA), and is assigned to the short arm of chromosome 6. The tight linkage between SCA1 and D6S89 has recently been reported. In order to examine possible locus heterogeneity, we studied linkage for D6S89 to disease loci in 16 pedigrees of dominant OPCA. D6S89 polymorphism was analysed with PCR amplification of genomic DNA by using specific oligonucleotide primers. Lod scores were computed by LIPED program with the correction of age-dependent penetrance. Homogeneity test was performed by using HOMOG program. Fifteen out of 16 pedigrees were informative to D6S89. Among them, 7 pedigrees showed positive and 8 pedigrees showed negative lod scores throughout all recombination fractions. Homogeneity testing disclosed that approximately 55% of pedigrees are linked to D6S89, and others were not linked. Our results provide evidences that dominant OPCA in Japan are genetically heterogenous. At now, it has been still unknown whether there are any clinico-pathological differences among OPCA genotypes. Based on the alpha-constant from homogeneity testing, we divided our pedigrees into linked-pedigree (SCA1) and nonlinked-pedigrees (nonSCA1). Then, clinical features were compared between these two groups. Hyperactive DTR was more common in SCA1 than nonSCA1 group. On the other hand, hypoactive DTR was more significantly dominated in nonSCA1 than SCA1. Slow saccade and Babinski sign were common in both groups. Although not statistically significant, nystagmus, exteral ophthalmoparesis, mydriasis, ptosis, facio-lingual twitching, and limb spasticity were more frequently observed in SCA1 than nonSCA1. These results indicate that there are possible correlation between disease genotype and phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Linkage study of hereditary olivopontocerebellar atrophy: genetic evidence for locus heterogeneity in Japanese cases]. 162 32

The authors report the case of a 12 year-old child who presented with a syndrome, isolated in Quebec, including spasticity, ataxia, distal muscle wasting, pes cavus, retinal striation, and the frequent presence of a prolapse of the mitral valve. This autosomal recessive disease is similar to Friedreich disease.
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PMID:[Recessive autosomal spastic ataxia]. 662 48

Fourteen patients (10 boys, 4 girls) aged from 4 months to 14 years old were diagnosed with mitochondrial disease based on the clinical manifestations together with abnormal muscle mitochondrial morphologies. Their clinical diagnoses included Leigh syndrome, three; Menkes' syndrome, three; Kearns-Sayre syndrome, two; myoclonic epilepsy with ragged fibres, one; and infant-onset progressive myoclonic epilepsy, one; fatal infantile mitochondrial myopathy, one; fatty acid oxidation defect, two; and myopathy with cardiopathy, one. Organs involved other than muscles included central nervous system, ten; heart, six; eye, two; liver, two; and kidney, two. Clinical manifestations varied to include hypotonia, seizures, myoclonus, mental retardation, nystagmus, ataxia, ptosis, ophthalmoplegia, retinal degeneration, muscle atrophy, spasticity etc. Nine had an abnormal rise in lactate after glucose loading. Ragged-red fibres were found in four patients. Abnormal mitochondrial morphology included abnormal accumulation, abnormal cristae pattern of tubular, concentric, or parallel form, some contained osmiophilic inclusion bodies. One patient of Leigh syndrome had had brain necropsy which showed intramyelin splitting of myelinated axons.
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PMID:Clinical manifestation of mitochondrial diseases in children. 821 54

We studied the clinical features and molecular genetics of a family, afflicted with a form of atypical parkinsonism, originating from the Madeira Islands of Portugal. We examined four affected individuals and reviewed clinical information on one other affected family member. Mean age at onset was 31 years. Parkinsonism (akinesia, rigidity, gait disturbance) was the most prominent feature in advanced disease. Levodopa responsiveness with peak-dose dyskinesia was present in one individual. Initial symptoms and other clinical features were variable and included other extrapyramidal signs (dystonia, action tremor of the limbs and bulbar muscles, synkinesis), ophthalmologic abnormalities (ptosis, slow saccades, progressive external ophthalmoplegia, hypometric saccades, saccadic pursuit movements), speech abnormalities (dysarthria, hypernasality), cortical impairment (dementia, frontal lobe dysfunction, palilalia, perseveration), minor cerebellar signs (dysmetria, gait ataxia), pyramidal abnormalities (spasticity, hyperreflexia), and peripheral nervous system abnormalities (propioceptive loss, areflexia, distal weakness, atrophy). The length of trinucleotide repeats in the MJD1 gene was in the normal range for all affected individuals.
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PMID:Atypical parkinsonism in a family of Portuguese ancestry: absence of CAG repeat expansion in the MJD1 gene. 915 59

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 70s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation an increasing number of patients practices a self-prescription with cannabis products for relieving a variety of symptoms. An anonymous standardized survey of the medical use of cannabis and cannabis products of patients in Germany, Austria and Switzerland was conducted by the Association for Cannabis as Medicine (Cologne, Germany). During about one year 170 subjects participated in this survey; questionnaires of 128 patients could be included into the evaluation. 68% of these participants were males, 32% females, with a total mean age of 37.5 (+/- 9.6) years. The most frequently mentioned indications for medicinal cannabis use were depression (12.0%), multiple sclerosis (10.8%), HIV-infection (9.0%), migraine (6.6%), asthma (6.0%), back pain (5.4%), hepatitis C (4. 8%), sleeping disorders (4.8%), epilepsy (3.6%), spasticity (3.6%), headache (3.6%), alcoholism (3.0%), glaucoma (3.0%), nausea (3.0%), disk prolapse (2.4%), and spinal cord injury (2.4%). The majority of patients used natural cannabis products such as marihuana, hashish and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription. About half of the 128 participants of the survey (52.4%) had used cannabis as a recreational drug before the onset of their illness. To date 14.3% took cannabis orally, 49.2% by inhalation and in 36.5% of cases both application modes were used. 72.2% of the patients stated the symptoms of their illness to have 'much improved' after cannabis ingestion, 23.4% stated to have 'slightly improved', 4.8% experienced 'no change' and 1.6% described that their symptoms got 'worse'. Being asked for the satisfaction with their therapeutic use of cannabis 60.8% stated to be 'very satisfied', 24.0% 'satisfied', 11.2% 'partly satisfied' and 4.0% were 'not satisfied'. 70.8% experienced no side effects, 26.4% described 'moderate' and 3.3% 'strong' side effects. 84.1% of patients have not felt any need for dose escalation during the last 3 months, 11.0% had to increase their cannabis dose 'moderately' and 4.8% 'strongly' in order to maintain the therapeutic effects. Thus, this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects. Because the patient group responding to this survey is presumably highly selected, no conclusions can be drawn about the quantity of wanted and unwanted effects of the medicinal use of the hemp plant for particular indications.
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PMID:[Results of a standardized survey on the medical use of cannabis products in the German-speaking area]. 2146 33

Botulinum toxins are potent neurotoxins used in a variety of neurological disorders. Few pediatric reports have been published to date regarding the potential hazards of therapeutic use of botulinum toxins. We describe the case of a 10-year-old boy who developed systemic weakness following treatment of spasticity with botulinum toxin type B. The patient developed iatrogenic botulism with ptosis, facial diplegia, neck flexor and extensor weakness, and profound hypopharyngeal laxity with respiratory compromise from which he eventually recovered. Clinicians should be mindful of the risk for systemic botulism when using local injections of the neurotoxin.
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PMID:Iatrogenic botulism in a child with spastic quadriparesis. 1794 Feb 53

Botulinum toxin blocks acetylcholine release at the neuromuscular junction. The drug which was initially found to be useful in the treatment of strabismus has been extremely effective in the treatment of variety of conditions, both cosmetic and noncosmetic. Some of the noncosmetic uses of botulinum toxin applications include treatment of spastic facial dystonias, temporary treatment of idiopathic or thyroid dysfunction-induced upper eyelid retraction, suppression of undesired hyperlacrimation, induction of temporary ptosis by chemodenervation in facial paralysis, and correction of lower eyelid spastic entropion. Additional periocular uses include control of synchronic eyelid and extraocular muscle movements after aberrant regeneration of cranial nerve palsies. Cosmetic effects of botulinum toxin were discovered accidentally during treatments of facial dystonias. Some of the emerging nonperiocular application for the drug includes treatment of hyperhidrosis, migraine, tension-type headaches, and paralytic spasticity. Some of the undesired side effects of periocular applications of botulinum toxin inlcude ecchymosis, rash, hematoma, headache, flu-like symptoms, nausea, dizziness, loss of facial expression, lower eyelid laxity, dermatochalasis, ectropion, epiphora, eyebrow and eyelid ptosis, lagophthalmos, keratitis sicca, and diplopia.
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PMID:Noncosmetic periocular therapeutic applications of botulinum toxin. 2061 16

We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2(Y616C) gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2(Y616C) complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other "mitochondrial" features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias.
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PMID:Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases. 2202 84

Spastic paraplegia type 7 is an autosomal recessive neurodegenerative disorder mainly characterized by progressive bilateral lower limb spasticity and referred to as a form of hereditary spastic paraplegia. Additional disease features may also be observed as part of a more complex phenotype. Many different mutations have already been identified, but no genotype-phenotype correlations have been found so far. From a total of almost 800 patients referred for testing, we identified 60 patients with mutations in the SPG7 gene. We identified 14 previously unreported mutations and detected a high recurrence rate of several earlier reported mutations. We were able to collect detailed clinical data for 49 patients, who were ranked based on a pure versus complex phenotype, ataxia versus no ataxia and missense versus null mutations. A generally complex phenotype occurred in 69% of all patients and was associated with a younger age at onset (trend with P = 0.07). Ataxia was observed in 57% of all patients. We found that null mutations were associated with the co-occurrence of cerebellar ataxia (trend with P = 0.06). The c.1409 G > A (p.Arg470Gln) mutation, which was found homozygously in two sibs, was associated with a specific complex phenotype that included predominant visual loss due to optical nerve atrophy. Neuropathology in one of these cases showed severe degeneration of the optic system, with less severe degeneration of the ascending tracts of the spinal cord and cerebellum. Other disease features encountered in this cohort included cervical dystonia, vertical gaze palsy, ptosis and severe intellectual disability. In this large Dutch cohort, we seem to have identified the first genotype-phenotype correlation in spastic paraplegia type 7 by observing an association between the cerebellar phenotype of spastic paraplegia type 7 and SPG7 null alleles. An overlapping phenotypic presentation with its biological counterpart AFG3L2, which when mutated causes spinocerebellar ataxia type 28, is apparent and possibly suggests that abnormal levels of the SPG7 protein impact the function of the mitochondrial ATPases associated with diverse cellular activities-protease complex (formed by SPG7 and AFG3L2) in the cerebellum. In addition, a missense mutation in exon 10 resulted in predominant optical nerve atrophy, which might suggest deleterious interactions of this SPG7 variant with its substrate OPA1, the mutated gene product in optic atrophy type 1. Functional studies are required to further investigate these interactions.
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PMID:Genotype-phenotype correlations in spastic paraplegia type 7: a study in a large Dutch cohort. 2296 62


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