Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alexander Disease (AxD) is a "gliopathy" caused by toxic, dominant gain-of-function mutations in the glial fibrillary acidic protein (GFAP) gene. Two distinct types of AxD exist. Type I AxD affected individuals develop cerebral symptoms by 4 years of age and suffer from macrocephaly, seizures, and physical and mental delays. As detection and diagnosis have improved, approximately half of all AxD patients diagnosed have onset >4 years and brainstem/spinal cord involvement. Type II AxD patients experience ataxia, palatal myoclonus, dysphagia, and dysphonia. No study has examined a mechanistic link between the GFAP mutations and caudal symptoms present in type II AxD patients. We demonstrate that two key astrocytic functions, the ability to regulate extracellular glutamate and to take up K(+) via K+ channels, are compromised in hindbrain regions and spinal cord in AxD mice. Spinal cord astrocytes in AxD transgenic mice are depolarized relative to WT littermates, and have a three-fold reduction in Ba(2+) -sensitive Kir4.1 mediated currents and six-fold reduction in glutamate uptake currents. The loss of these two functions is due to significant decreases in Kir4.1 (>70%) and GLT-1 (>60%) protein expression. mRNA expression for KCNJ10 and SLC1A2, the genes that code for Kir4.1 and GLT-1, are significantly reduced by postnatal Day 7. Protein and mRNA reductions for Kir4.1 and GLT-1 are exacerbated in AxD models that demonstrate earlier accumulation of GFAP and increased Rosenthal fiber formation. These findings provide a mechanistic link between the GFAP mutations/overexpression and the symptoms in those affected with Type II AxD.
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PMID:Elevated GFAP induces astrocyte dysfunction in caudal brain regions: A potential mechanism for hindbrain involved symptoms in type II Alexander disease. 2619 Apr 8

We describe the case of a 15-year-old male with early juvenile type GM2 gangliosidosis. He first manifested with progressive clumsiness in his extremities at the age of 1.5 years, followed by motor regression. Intellectual disability became evident as late as age 6 years. This discrepancy along with rapid motor deterioration after varicella infection, lack of startle response or macrocephaly, and paucity of myoclonus were thought to be characteristic of juvenile GM2 gangliosidosis. In contrast to the cerebellar atrophy as the initial finding in usual juvenile GM2 gangliosidosis, magnetic resonance imaging revealed initially cerebral, and subsequently cerebellar, progressive atrophy. Autistic behavioral problems, including phonophobia, during intellectual regression in this patient was also unusual in juvenile GM2 gangliosidosis. Thus, recognition of these features would prompt proper diagnosis and insights into the pathomechanisms of GM2 gangliosidosis.
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PMID:[Clinical characteristics of early juvenile GM2 gangliosidosis: a case report]. 3011 98