A proportion of patients with peripheral neuropathies has circulating autoantibodies directed against neural antigens. In some cases, autoantibodies may play a pathogenic role. We studied a patient ...with a progressive sensory-motor axonal neuropathy of unknown etiology, looking for circulating autoantibodies against neural antigens and we showed that the patient's serum contained anti-amphiphysin I (AMP I) and amphiphysin II (AMP II) autoantibodies. A sural nerve biopsy revealed an axonal neuropathy. Indirect immunofluorescence experiments with the patient's serum showed a staining of rat axons due to alpha-AMP I autoantibodies and a specific labelling of cytoplasm and Schmidt-Lanterman incisures of Schwann cells due to alpha-AMP II autoantibodies. In conclusion we identified a patient affected by a sensory-motor neuropathy with autoantibodies against both AMP I and AMP II.
The aim is to provide an up-to-date overview of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome with special regard to the available therapy ...options.
In the past 20 years this rare plasmaproliferative disorder has been extensively characterized from a clinical point of view with complete description of the typical features as well as of other organ involvement not considered in the acronym as nephropathy or pachimeningitis. In this syndrome, the serum levels of vascular endothelial growth factor (VEGF) are abnormally elevated and now this is considered one of the major criteria for making the diagnosis. VEGF has also a prognostic value, as it decreases in response to therapy and definitely has a pathogenetic role in the multisystem involvement of POEMS. Recently great advance occurred in the treatment of POEMS syndrome with new immunomodulatory drugs such as lenalidomide, autologous peripheral blood stem cell transplantation or bevacizumab, an anti-VEGF monoclonal antibody.
Although many aspects of POEMS syndrome remain unclear, a valid biomarker of disease, VEGF, is available for diagnosis as well as a wide range of therapeutic options.
Spinal muscular atrophy (SMA) is an autosomal recessive genetic motor neuron disorder caused by a defect in the survival motor neuron 1 (SMN1) gene resulting from deletions or other mutations. The ...number of copies of SMN2, a gene paralogous to SMN1, modifies clinical course. The homozygous deletion of exon 7 is the most recurrent molecular defect but heterozygous deletions in compound with single nucleotide intragenic mutations have also been reported. We describe the clinical and molecular features of a child born to not consanguineous parents who developed a severe muscle hypotonia at 10days of age. Clinical diagnosis was compatible with SMA type I (Werdnig–Hoffmann) phenotype. SMA locus genotype by quantitative PCR analysis revealed one copy of both SMN1 and SMN2 genes. Sequence analysis in the proband disclosed the heterozygous novel c.888+1G>C substitution affecting the donor splice site between exon 7 and intron 7. The deletion and the point mutation are independently inherited from the parents. Standard and quantitative RT-PCR experiments on proband’s cDNA disclosed a severe reduction of the full-length/delta7 ratio of SMN isoforms as well as the presence of a transcript originating from SMN1 but lacking exon 7. Approximately 3–5% of patients with SMA retain at least one copy of the SMN1 gene carrying pathogenic insertions, deletions, or point mutations on the other allele. The number of intragenic mutations affecting splicing is even narrower. Our findings demonstrate that the novel c.888+1G>C mutation is highly deleterious, resulting in the almost total exclusion of exon 7. Sequence analysis is helpful to identify these defects whose effects might be highly detrimental on SMN stability and function.
Hypokalemic periodic paralysis (HypoPP) is a rare disorder consisting of sudden episodes of muscle weakness with areflexia involving all four limbs, which spontaneously resolve within several hours ...or days. Primary HypoPP is genetically determined, while secondary acquired HypoPP has been described in association with thyreotoxycosis, hyperaldosteronism, kidney diseases, diuretics and liquorice abuse, gastrointestinal potassium loss, or cysplatinum therapy.
To report a case of HypoPP associated with GH deficiency.
A 33 yr-old man with hypopituitarism and diabetes insipidus secondary to pituitary stalk-localized sarcoidosis, and documented HypoPP episodes.
Neurologic exam outside HypoPP episodes was normal. Needle electromyography was normal without myotonia or other spontaneous electric activity. Muscle biopsy documented a vacuolar myopathy with tubular aggregates. However, genetic analysis ruled out common mutations of the voltage-gated calcium channel observed in primary HypoPP. Common causes of secondary HypoPP were also ruled out. The patient was diagnosed with severe GH deficiency with modest fasting hyperinsulinemia and insulin resistance and started on GH replacement therapy, an alpha-glucosidase inhibitor (acarbose) and a diet low in simple carbohydrates.
GH replacement therapy, acarbose and a diet low in simple carbohydrates resulted in the complete long-term (>2 yr) remission of HypoPP episodes. This is consistent with the hypothesis that the hyperinsulinemia associated to GH deficiency may trigger HypoPP episodes by increasing Na+/K+ ATPase activity and K+ transport into the intracellular compartment with subsequent hypokalemia.
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