Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An unusual association of Klippel-Feil syndrome and other abnormalities (Sprengel's deformity, 1st cervical and 1st dorsal spina bifida, homovertebral bone, scoliosis, plagiocephaly, basilar impression, pterygium colli, nanism, hypogenitalism, etc.) together with neurological signs of amyotrophic lateral sclerosis, in a 36-yr-old woman is reported. The clinical and radiological pictures are examined and the exterior morphology is examined. The three types of Klippel-Feil syndrome are discussed, together with the particular alterations observed in the present case: Sprengel's deformity, spina bifida, craniostenosis, basilar impression, etc.
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PMID:[Klippel-Feil syndrome and associated malformations. Comments on an unusual case]. 109 66

Neuromuscular and chest wall disorders are individually uncommon but together form an important group of conditions that can lead to chronic ventilatory failure. This is best recognised in scoliosis, kyphosis, following a thoracoplasty, in muscular dystrophies, such as Duchenne muscular dystrophy (DMD), and myotonic dystrophy, after poliomyelitis and with motor neurone disease (amyotrophic lateral sclerosis). If bulbar function is impaired, tracheostomy ventilation may be required, but in other situations, noninvasive ventilation is preferable. Positive pressure techniques using nasal and face masks are usually the first choice, but negative pressure ventilation is an alternative. There are no randomised-controlled trials regarding the indications for initiating noninvasive ventilation, but this is usually provided if there are symptoms due to nocturnal hypoventilation or right heart failure in the presence of a raised carbon dioxide tension in arterial blood (Pa,CO2) either at night or, more usually, in the daytime as well. There is no evidence that "prophylactic" ventilatory support is of benefit if this is provided before ventilatory failure has appeared. Careful selection of patients is required, especially in the presence of progressive neuromuscular disorders such as DMD and motor neurone disease. There are no randomised-controlled trials concerning the outcome of noninvasive ventilation in these conditions, but studies have shown an improved quality of life, physical activity and haemodynamics, normalisation of blood gases and slight improvement in other physiological measures, such as the vital capacity and maximal mouth pressures. Survival in chest wall disorders is approximately 90% at 1 yr and 80% at 5 yrs, and similar figures have been obtained in nonprogressive neuromuscular conditions. If, however, the underlying disorder is deteriorating, particularly if it involves the bulbar muscles, it may limit survival despite the provision of adequate noninvasive ventilatory support.
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PMID:Noninvasive ventilation for chest wall and neuromuscular disorders. 1508 69

Home mechanical ventilation (HMV) is increasingly used as a therapeutic option to patients with symptomatic chronic hypoventilation. There is, however, a paucity of solid data on factors that could affect prognosis in patients on home ventilation. In the present study, our aim was to study several factors in these patients with potential influence on survival. We examined 1526 adult patients from a nationwide HMV register to which data had been reported prospectively for 10 years. The patients constituted a broad diagnostic spectrum and the primary outcome in this study was death. We found by far the poorest survival rate in the ALS patients with only 5% alive after 5 years. Among the other patient groups the survival pattern was more uniform and the scoliosis, polio and Pickwick patients presented the best survival rate, after 5 years being around 75%. No factors were associated with a greater hazard for death in the ALS patients; in the non-ALS patients, however, negative predictors for survival were age, concomitant use of oxygen therapy, tracheostomy ventilation and start of ventilatory support in an acute clinical setting. Center size or county specific home ventilation treatment prevalence did not affect survival. In conclusion, in a large material of patients on HMV we found by far the poorest survival in the ALS patients. In the non-ALS patients a number of patient-related factors affected survival, while the size of the treating center or the regional treatment prevalence did not.
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PMID:Survival of patients on home mechanical ventilation: a nationwide prospective study. 1710 79

This article reviews the recent literature regarding bone health as it relates to the patient living with neuromuscular disease (NMD). Studies defining the scope of bone-related disease in NMD are scant. The available evidence is discussed, focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and spinal muscular atrophy. Future directions are discussed, including the urgent need for studies both to determine the nature and extent of poor bone health, and to evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD.
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PMID:Bone health and associated metabolic complications in neuromuscular diseases. 2313 37

Klippel-Feil syndrome (KFS) is an unusual skeletal disorder characterized by congenital fusion of two or more cervical vertebrae which can be sporadic or familial. KFS emerges to be a failure of the normal segmentation and fusion of the mesodermal somites during 3(rd) and 8(th) weeks of embryonic development. The triad of low posterior hairline, short neck, and restricted neck motion is present only in 50% and often associated with scoliosis, spina bifida, Sprengel's deformity, cervical ribs, deafness, cleft palate, renal anomalies, congenital heart defects, and so on because of heterogeneous nature of the disease. The significance of KFS lies in the secondary effects produced on the nervous system, which usually presents with features of progressive cord and brain stem compression with relatively minor trauma. We here report two cases of KFS presented in association with amyotrophic lateral sclerosis. Only two such cases have been described in the literature in 1954 and 1975.
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PMID:Two case reports of an unusual association between Klippel-Feil syndrome and amyotrophic lateral sclerosis: Do they share same genetic defect? 2433 16

The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.3512+1G>A) in the ALS2 gene (NM_020919.3) encoding alsin that segregated with the disease in this family. Homozygous loss-of-function mutations in ALS2 are known to cause juvenile-onset amyotrophic lateral sclerosis (ALS), one of the many neurological conditions having overlapping symptoms with many neurological phenotypes. RT-PCR validation revealed that the mutation resulted in exon-skipping as well as the use of an alternative donor splice, both of which are predicted to cause loss-of-function of the resulting proteins. By examining 216 known neurological disease genes in our exome sequencing data, we also identified 9 other rare nonsynonymous mutations in these genes, some of which lie in highly conserved regions. Sequencing of a single proband might have led to mis-identification of some of these as the causative variant. Our findings established a firm diagnosis of juvenile ALS in this family, thus demonstrating the use of whole exome sequencing combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.
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PMID:A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias. 2547 99

The patient was a 29-year-old male. He took his first steps at two-and-a-half years old, but his physical strength deteriorated and he became non-ambulatory at 12 years old. He had respiratory failure at the age of 20, and finally underwent tracheostomy with invasive positive-pressure ventilation (TPPV). He showed distal dominant muscle weakness and atrophy, including the face. Spinal scoliosis was recognized. He had peripheral predominance of sensory disorders. Nerve conduction studies showed a decrease of compound muscle action potential and a reduction of motor nerve conduction velocity. Sensory nerve action potential was not evoked. In genetic analysis, c.23 C> T (p. T8M) heterozygous mutation was found in the senataxin gene (SETX). Although SETX is a causative gene of familial amyotrophic lateral sclerosis type 4 (ALS4), this case suggests that SETX mutation can also cause motor and sensory polyneuropathy.
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PMID:[A case of motor and sensory polyneuropathy and respiratory failure with novel heterozygous mutation of the senataxin gene]. 3253 63

Recently markerless 3D scanning methods receive an increased interest for therapy planning and brace treatment of patients with scoliosis. This avoids repeated radiation known from standard X-Ray analysis. Several authors introduced the method of asymmetry distance maps in order to classify curve severity and progression. The current work extends this approach by statistical mean shape 3D models of the human trunk in order to classify patients. 50 patients were included in this study performing frontal X-ray and 3D scanning analysis. All patients were classified by a clinician according to their Cobb angle and spinal curve pattern (Augmented-Lehnert-Schroth ALS). 3D reconstructions of each patient trunk were processed in a way to elastically register a reference surface mesh with fixed number of data points. Mean 3D shape models were generated for each curve pattern. An asymmetry distance map was then calculated for each patient and mean shape model. Single patient 3D reconstructions were classified according to severity and ALS treatment group. Optimal sensitivity and specificity was 97%/39% thoracic and 87%/42% lumbar respectively for detecting mild and moderate-severe patients. Identifying a treatment group was possible for three combined groups allowing to support decisions during diagnosis and therapy planning.
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PMID:Innovative decision support for scoliosis brace therapy based on statistical modelling of markerless 3D trunk surface data. 3254 33