Peripheral Ataxia Research Articles

Clinical and Molecular Characteristics of A Novel Homozygous DNAJC3 Gene Variant in a Saudi family

Combined cerebellar and peripheral ataxia with hearing loss and diabetes mellitus is an extremely rare neurodegenerative disorder affecting the central and peripheral nervous systems. The pathogenesis of widespread neurodegeneration in previously reported cases with homozygousDNAJC3mutations is proposed to be caused by a common etiology that is mitochondrial dysfunction and loss of mitigation of the endoplasmic reticulum stress response. In this paper, we reported a rare case of combined cerebellar and peripheral ataxia with hearing loss and diabetes mellitus in a Saudi family with a novel homozygous stop-gain mutation c.1177C>T p.(Arg393*) in exon 10 of the DNAJC3 gene, which creates a premature stop codon.The advances in genetic testing, including whole exome sequencing, have increased our knowledge of mitochondrial disorders, monogenic diabetes, and homozygous DNAJC3mutations phenotype who presents with juvenile-onset diabetes mellitus and multiple symptoms and signs of neurodegenerative disease, DNAJC3mutation should be suspected. Keywords: DNAJC3; Combined Cerebellar and Peripheral Ataxia with Hearing Loss and Diabetes Mellitus; Autosomal Recessive; Mutation; Saudi Arabia.

Neuromuscular Manifestations in Mitochondrial Diseases in Children

Mitochondrial diseases exhibit significant clinical and genetic heterogeneity. Mitochondria are highly dynamic organelles that are the major contributor of adenosine triphosphate, through oxidative phosphorylation. These disorders may be developed at any age, with isolated or multiple system involvement, and in any pattern of inheritance. Defects in the mitochondrial respiratory chain impair energy production and almost invariably involve skeletal muscle and peripheral nerves, causing exercise intolerance, cramps, recurrent myoglobinuria, or fixed weakness, which often affects extraocular muscles and results in droopy eyelids (ptosis), progressive external ophthalmoplegia, peripheral ataxia, and peripheral polyneuropathy. This review describes the main neuromuscular symptomatology through different syndromes reported in the literature and from our experience. We want to highlight the importance of searching for the "clue clinical signs" associated with inheritance pattern as key elements to guide the complex diagnosis process and genetic studies in mitochondrial diseases.

Mutations in VLDLR as a Cause for Autosomal Recessive Cerebellar Ataxia With Mental Retardation (Dysequilibrium Syndrome)

Dysequilibrium syndrome is a genetically heterogeneous condition that combines autosomal recessive, nonprogressive cerebellar ataxia with mental retardation. Here, we report the first patient heterozygous for 2 novel mutations in VLDLR. An 18-month-old girl presented with significant hypotonia, global developmental delay, and truncal and peripheral ataxia. Magnetic resonance imaging of the brain demonstrated hypoplasia of the inferior cerebellar vermis and hemispheres, small pons, and a simplified cortical sulcation pattern. Sequence analysis of the VLDLR gene identified a nonsense and missense mutation. Six mutations in VLDLR have now been identified in 5 families with a phenotype characterized by moderate-to-profound mental retardation, delayed ambulation, truncal and peripheral ataxia, and occasional seizures. Neuroanatomically, the loss-of-function effect of the different mutations is indistinguishable. VLDLR-associated cerebellar hypoplasia is emerging as a panethnic, clinically, and molecularly well-defined genetic syndrome.

Radiologic aspects of thallium poisoning.

The authors have recently encountered at the Hospital Dos de Mayo, Lima, Peru, 5 cases of thallium intoxication within a period of approximately one and a half years. In 1 instance a dense abdominal shadow corresponding to the liver was discovered by chance on roentgenograms obtained in an examination of the lumbosacral spine because of complaints of discomfort in that area. In this article, the clinical and experimental findings of the condition will be described, with stress laid on the roentgen features. Case Report G. J. O., a 22-year-old male, was brought by his family, against his will, to the hospital on Nov. 16, 1961, with a 16-day history of anorexia, epigastric pain, vomiting, myalgias, arthralgias, paresthesias, and hyperesthesias, principally in the arms and legs, but also in the lower back. The physical findings were considered unreliable because of the patient's lack of co-operation. He was moderately dehydrated and in no acute distress. There were muscular pains, especially when the arms and legs were pressed, epigastric tenderness, peripheral ataxia, deep tendon reflexes hyperactive throughout, and a blood pressure of 150/50. The weight was 55 kg. and the height 162 cm. Laboratory examination: The peripheral blood showed an erythrocyte count of 4,240,000 per cubic millimeter and a white blood count of 7,000 per cubic millimeter; the differential formula was normal. The hemoglobin was 12.6 gm. per ml. The urinalysis and hepatic function tests showed normal findings as did the examination of the sedimentation rate, the fasting blood sugar levels, the blood-urea-nitrogen, the clotting and bleeding times, and the creatinine blood levels. The serum electrolyte levels showed hyponatremia. No clinical improvement was obtained with symptomatic treatment of fluids, analgesics, and barbiturates. Alopecia began to develop four days after admission; on this day a roentgen bone survey was made. The roentgenogram obtained in examination of the lumbar spine revealed a normal bone structure and a high-density intra-abdominal mass, probably corresponding to increased liver radiopacity (Fig. 1). Thallium poisoning was suspected, and finally the patient confessed he had ingested 2 tubes of Zelio paste four days before the onset of his symptoms, after a “quarrel with his girl friend.” (Each tube of Zelio paste contains 28 grams of paste with thallium sulfate in a 2.33 per cent concentration.) The diagnosis of thallotoxicosis was confirmed by positive thallium determinations in the nails, hair, blood, and urine, by use of the spectrophotometric method of Van Aman and Hanselmeyer (10). At the same time a spinal fluid sample was obtained, but the chemical and bacteriological examinations were normal, and there was no measurable amount of thallium. Progressive improvement followed the daily administration for fifteen days of 200 mg. of B.A.L. (2,3-dimercaptopropanol), divided into two equal doses of 100 mg. each.