The PR of all adult NMD in RoI is relatively high when compared with other chronic neurologic disorders, although some figures may be an underestimate of the true prevalence. The data provide a framework for international comparison and service planning.
SummaryA previously healthy 35-year-old Caucasian woman developed left body (including facial) hemianaesthesia, asymmetrical lower cranial nerve palsies and cerebellar signs after a 4-day history of headache, nausea and vomiting. Serial blood and cerebrospinal fluid (CSF) cultures returned negative for a culprit organism. CSF examination revealed a lymphocytic pleocytosis and an elevated protein count. CSF cytological examination identified plasma cells. MRI of brain showed multiple ring-enhancing 'abscess-like' lesions in the brainstem and upper cervical cord together with abnormal meningeal enhancement. A decision was made to treat her empirically for Listeria rhombencephalitis to which she responded completely. CSF PCR eventually returned positive for Listeria monocytogenes. This case illustrates the utility of clinical features, MRI, CSF cytology and PCR in diagnosis and treatment of culture negative L monocytogenes rhombencephalitis in an immunocompetent individual. BACKGROUND
Background Background: Late-onset Tay-Sachs disease (LOTS) is an autosomal-recessive lysosomal storage disease caused by deficient β-hexosaminidase A activity. LOTS is rare in the Ashkenazi Jews, but even rarer in the non-Jewish population. Cases Cases: We report an Irish family expanding the LOTS phenotype (ataxia, diffuse muscle wasting, dystonia, chorea, belly dancer's dyskinesia, and neuropsychiatric features) associated with the known HEXA variant 1073 + 1G > A and a novel variant c.459 + 24G > C. Conclusions Conclusions: LOTS should be considered in patients with similar symptoms and cerebellar atrophy on brain imaging. Late-onset Tay-Sachs disease (LOTS) is an autosomal-recessive disorder attributed to HEXA mutations causing reduced β-hexosaminidase A activity and subsequent CNS ganglioside accumulation. Affected individuals can present from late childhood with slowly progressive and heterogenous clinical manifestations such as cerebellar dysfunction, anterior horn cell pathology mimicking spinal muscular atrophy, and extrapyramidal and psychiatric features. 1 LOTS is rare in the Ashkenazi Jewish (1:135,000). 1 In the non-Jewish, LOTS is much scarcer and associated with extreme mutation heterogeneity, often with private or unique alleles. 2 We report an Irish family with LOTS, harboring a novel HEXA variant, and present videos of 3 siblings demonstrating heterogenous clinical manifestations including extrapyramidal, spinocerebellar, and neuropsychiatric involvement. Case Series A family pedigree showing genotypes are illustrated in Figure 1. Clinical, biochemical, and MRIbrain characteristics for patients II.4, II.5, II.6, and II.9 are illustrated in Table 1. Genetic Analysis Molecular analysis of the HEXA gene was performed at the Department of Clinical Genetics Amsterdam, the Netherlands. All coding sequences of the HEXA gene, including the flanking intron sequences, were analyzed by direct sequencing. Large deletions or insertions were excluded using Multiplex Ligation Dependent Probe Amplification analysis P199 from MRC Holland (www.mrc-holland.com). HEXA gene DNA analysis detected a previously reported heterozygous mutation c. 1073 + 1G > A and a previously unpublished c.459 + 24G > C variant in all 4 affected siblings (II.4. II.5, II.6, and II.9). The mother (I.2) was heterozygous for c. 1073 + 1G > A. An unaffected sister (II.10) tested negative for both variants. The rest of the family members were not available for testing (Fig. 1A). The variant c.459 + 24G > C has not been described before, and as splicing prediction modules (Alamut Visual 2.7.1) did not predict splicing defects, it is classified as class 3 (pathogenicity unclear). Case 1 (II.4 Proband) This 56-year-old man, born to nonconsanguineous parents of non-Jewish European ancestry, presented with a 10-year history
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.
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