105 research outputs found
Adult-onset cerebellar Ataxia: a clinical and genetic Survey
Cerebellar ataxias represent a heterogeneous group of neurodegenerative disorders.
Two main categories are distinguished: hereditary and sporadic ataxias. Sporadic
ataxias may be symptomatic or idiopathic. The clinical classification of hereditary
ataxias is nowadays being replaced by an expanding genotype-based classification.
A large spectrum of degenerative and metabolic disorders may also present with
ataxia early or late in the course of disease. We present a diagnostic algorithm for the
adult patient presenting with subacute cerebellar ataxia, based on family history and
straightforward clinical characteristics of the patient. Along with the algorithm, an
overview of the autosomal dominant, autosomal recessive, X-linked, mitochondrial,
symptomatic and idiopathic subtypes of cerebellar ataxia is presented. An appropriate
diagnosis is of utmost importance to such considerations as prognosis, genetic
counseling and possible therapeutic implications
Home-based enzyme replacement therapy in children and adults with Pompe disease; a prospective study
Discontinuation of enzyme replacement therapy in adults with Pompe disease: Evaluating the European POmpe Consortium stop criteria
Enzyme replacement therapy for Pompe disease received market authorization in 2006. To implement this costly treatment in the Netherlands in the most sensible way, a multidisciplinary expert committee was installed. We evaluated decision making in adult patients in relation to the European POmpe Consortium stop criteria. Of 125 adult Pompe patients, 111 started treatment; subsequently treatment stopped in 24 patients (21%). In 10 patients, treatment was discontinued for medical or personal reasons, as defined in the six stop criteria (median treatment duration: 2.1 years, range: 0.3–14.6 years). Three of these patients continued follow-up (follow-up: 1.3–8.0 years), these patients did not display a more rapid decline after discontinuation. In 14 of 24 patients, therapy ended at time of death. In 10 patients death was related to Pompe disease (median treatment duration: 7.2 years, range: 0.4–10.3 years). All 10 patients were severely affected at start of treatment, treatment had elicited positive effects in eight. The European POmpe Consortium guidelines worked well in decision making on stopping treatment. However, (re)evaluation of the rationale for continuation of treatment in advanced disease stage is not addressed. We suggest to add this to the treatment evaluation and to handle treatment decisions in a multidisciplinary expert team
Increased aortic stiffness and blood pressure in non-classic Pompe disease
Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99)
A detailed description of the phenotypic spectrum of North Sea Progressive Myoclonus Epilepsy in a large cohort of seventeen patients
Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy after alemtuzumab therapy in kidney transplant recipients
Clinical and pathologic phenotype of a large family with heterozygous STUB1 mutation
Objective
To describe the clinical and pathologic features of a novel pedigree with heterozygous STUB1
mutation causing SCA48.
Methods
We report a large pedigree of Dutch decent. Clinical and pathologic data were reviewed, and
genetic analyses (whole-exome sequencing, whole-genome sequencing, and linkage analysis)
were performed on multiple family members.
Results
Patients presented with adult-onset gait disturbance (ataxia or parkinsonism), combined with
prominent cognitive decline and behavioral changes. Whole-exome sequencing identified
a novel heterozygous frameshift variant c.731_732delGC (p.C244Yfs*24) in STUB1 segregating with the disease. This variant was present in a linkage peak on chromosome 16p13.3.
Neuropathologic examination of 3 cases revealed a consistent pattern of ubiquitin/p62-positive
neuronal inclusions in the cerebellum, neocortex, and brainstem. In addition, tau pathology was
present in 1 case.
Conclusions
This study confirms previous findings of heterozygous STUB1 mutations as the cause of SCA48
and highlights its prominent cognitive involvement, besides cerebellar ataxia and movement
disorders as cardinal features. The presence of intranuclear inclusions is a pathologic hallmark
of the disease. Future studies will provide more insight into its pathologic heterogeneity
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