Subject(s)
Phenotype , RNA Polymerase III , Humans , RNA Polymerase III/genetics , RNA Polymerase III/immunology , Male , Female , MutationABSTRACT
BACKGROUND AND PURPOSE: Tay-Sachs disease is a rare and often fatal, autosomal recessive, lysosomal storage disease. Deficiency in ß-hexosaminidase leads to accumulation of GM2 ganglioside resulting in neuronal swelling and degeneration. Typical onset is in infancy with developmental regression and early death. Late-onset Tay-Sachs disease (LOTS) is extremely rare, especially in the non-Ashkenazi Jewish population, and is characterized by a more indolent presentation typically encompassing features of cerebellar and anterior horn cell dysfunction in addition to extrapyramidal and neuropsychiatric symptoms. CASES: A case series of four unrelated patients of non-Ashkenazi Jewish origin with a predominantly, and in some cases pure, neuromuscular phenotype with evidence of a motor neuronopathy on electromyography is presented. Cerebellar atrophy, reported to be a ubiquitous feature in LOTS, was absent in all patients. CONCLUSION: This case series provides evidence to support a pure neuromuscular phenotype in LOTS, which should be considered in the differential diagnosis of anterior horn cell disorders.
Subject(s)
Mental Disorders , Tay-Sachs Disease , Humans , Tay-Sachs Disease/diagnosis , Tay-Sachs Disease/genetics , Tay-Sachs Disease/psychology , Phenotype , CerebellumABSTRACT
Andersen-Tawil syndrome (ATS) is a rare autosomal dominant potassium channelopathy characterized by a triad of periodic paralysis, ventricular arrhythmias, and distinctive dysmorphic abnormalities. We present a 19-year-old man with characteristic skeletal dysmorphic features of ATS, early nonfluctuating proximal lower limb weakness from childhood, and neonatal focal seizures. He later developed fluctuating weakness in addition to a fixed proximal myopathy. A 12-lead electrocardiogram showed prominent "U" waves, and McManis protocol prolonged exercise test showed an unusually early decline in the compound motor action potential amplitude by 51%. Genetic testing revealed a de novo heterozygous mutation (R218W) in KCNJ2 associated with ATS. This is the first reported case of ATS in an Irish population with an unusual fixed myopathy from early childhood.
Subject(s)
Andersen Syndrome/complications , Muscular Diseases/genetics , Andersen Syndrome/genetics , Andersen Syndrome/pathology , Humans , Male , Mutation , Potassium Channels, Inwardly Rectifying/genetics , Young AdultABSTRACT
BACKGROUND: Several conditions have been reported to mimic motor neuron disease (MND), and misdiagnosis remains a common clinical problem. OBJECTIVE: To report a case of bulbar-onset polymyositis where the initial clinical presentation was suggestive of MND. CASE DESCRIPTION: A 73-year-old woman was admitted for investigation of acute-onset dysphagia without dysarthria. Examination revealed nasal dysphonia and severe oropharyngeal weakness. Subtle upper-limb weakness, brisk tendon reflexes, and fasciculations in the right deltoid muscle were also demonstrated. A clinical diagnosis of MND was entertained. The serum creatine kinase value was within the reference range. Findings from electromyographic studies, however, were suggestive of a myopathic rather than a neurodegenerative process, and a muscle biopsy specimen was diagnostic of polymyositis. The dysphagia rapidly resolved upon treatment with corticosteroids and azathioprine. CONCLUSIONS: Bulbar-onset polymyositis may mimic MND, particularly in the absence of inflammatory markers or elevated muscle enzyme levels. Caution should be exercised in the clinical diagnosis of bulbar dysfunction, and further investigations such as electromyography and muscle biopsy are indicated to confirm the diagnosis.
