Five years experience on 3,4-diaminopyridine phosphate in Lambert-Eaton syndrome: Case reports
Abstract Rationale: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert–Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. Patient concerns: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (…
Acute onset of bulbar amyotrophic lateral sclerosis after flu – look at the differential diagnosis: A case report
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper and lower motor neurones. It can be either familial (fALS) or sporadic (sALS). ALS is characterized by muscle weakness and atrophy that can involve the limbs and trunk (i.e. the spinal form of the disease) or speech and swallowing (i.e. the bulbar form). The aetiology of sALS remains unclear although a gene–environment interaction has been proposed as a concomitant trigger for the neurodegenerative process together with viral infections, smoking, heavy metals and pesticide exposure. Herein, we report the case of a 67-year-old woman who experienced an acute onset of bulbar ALS with an atypical clinical cours…
Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification
International audience; Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromo…
Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment
VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved resid…
PDXK mutations cause polyneuropathy responsive to pyridoxal 5′‐phosphate supplementation
OBJECTIVE: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating sc…
C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population.
It has been recently reported that a large proportion of patients with familial amyotrophic lateral sclerosis (familial ALS) and frontotemporal dementia (FTD) are associated with a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72. We have assessed 1,757 Italian sporadic ALS cases, 133 from Sardinia, 101 from Sicily, and 1,523 from mainland Italy. Sixty (3.7%) of 1,624 mainland Italians and Sicilians and 9 (6.8%) of the 133 Sardinian sporadic ALS cases carried the pathogenic repeat expansion. None of the 619 regionally-matched control samples (1,238 chromosomes) carried the expansion. Twenty-five cases (36.2%) had behavioral FTD in addition to ALS. FTD or unspecified d…