The Prevalence of Fabry Disease Among Young Cryptogenic Stroke Patients.

Introduction Fabry disease is a metabolic storage disorder that causes disorders in multiple organs including the brain. Data regarding the prevalence of the disease among the Saudi stroke population is scarce. Hence, tests for the same are not conducted on a regular basis when investigating stroke of uncertain cause. Our study aimed to provide insight into whether testing for Fabry disease is justifiable in cryptogenic stroke patients who have no other features of the disease. Method This was a prospective study conducted at a single stroke center. We included young patients between the ages of 18 and 55 years who had confirmed and unexplained ischemic or hemorrhagic insults. Alpha-galactosidase enzyme testing was conducted in all suspected cases. Further genetic testing was performed in patients with abnormal enzyme results. Result A total of 51 patients met the inclusion criteria. The mean age was 42 years. All the included patients completed a workup of ischemia or hemorrhage. All cases had no clear etiology of their vascular events. All included patients lacked classic systemic manifestations of Fabry disease. We identified one case of borderline low α-galactosidase A (GLA) enzyme level. However, GLA genetic testing did not reveal any Fabry disease-related mutation. The study did not identify any subject with confirmed Fabry disease. Conclusion In this single-center study, we found that Fabry disease had a low prevalence among Saudi cryptogenic stroke patients who lack other systemic manifestations. Hence, Fabry testing is not generally considered in routine workup related to cryptogenic stroke.

Diagnosis and treatment of late-onset Pompe disease in the Middle East and North Africa region: consensus recommendations from an expert group.

BACKGROUND: Pompe disease is a rare autosomal recessive disorder caused by a deficiency of the lysosomal enzyme alpha-glucosidase responsible for degrading glycogen. Late-onset Pompe disease has a complex multisystem phenotype characterized by a range of symptoms. METHODS: An expert panel from the Middle East and North Africa (MENA) region met to create consensus-based guidelines for the diagnosis and treatment of late-onset Pompe disease for the MENA region, where the relative prevalence of Pompe disease is thought to be high but there is a lack of awareness and diagnostic facilities. RESULTS: These guidelines set out practical recommendations and include algorithms for the diagnosis and treatment of late-onset Pompe disease. They detail the ideal diagnostic workup, indicate the patients in whom enzyme replacement therapy should be initiated, and provide guidance on appropriate patient monitoring. CONCLUSIONS: These guidelines will serve to increase awareness of the condition, optimize patient diagnosis and treatment, reduce disease burden, and improve patient outcomes.

Redox state and mitochondrial respiratory chain function in skeletal muscle of LGMD2A patients.

BACKGROUND: Calpain-3 deficiency causes oxidative and nitrosative stress-induced damage in skeletal muscle of LGMD2A patients, but mitochondrial respiratory chain function and anti-oxidant levels have not been systematically assessed in this clinical population previously. METHODS: We identified 14 patients with phenotypes consistent with LGMD2A and performed CAPN3 gene sequencing, CAPN3 expression/autolysis measurements, and in silico predictions of pathogenicity. Oxidative damage, anti-oxidant capacity, and mitochondrial enzyme activities were determined in a subset of muscle biopsies. RESULTS: Twenty-one disease-causing variants were detected along the entire CAPN3 gene, five of which were novel (c.338 T>C, c.500 T>C, c.1525-1 G>T, c.2115+4 T>G, c.2366 T>A). Protein- and mRNA-based tests confirmed in silico predictions and the clinical diagnosis in 75% of patients. Reductions in antioxidant defense mechanisms (SOD-1 and NRF-2, but not SOD-2), coupled with increased lipid peroxidation and protein ubiquitination, were observed in calpain-3 deficient muscle, indicating a redox imbalance primarily affecting non-mitochondrial compartments. Although ATP synthase levels were significantly lower in LGMD2A patients, citrate synthase, cytochrome c oxidase, and complex I+III activities were not different from controls. CONCLUSIONS: Despite significant oxidative damage and redox imbalance in cytosolic/myofibrillar compartments, mitochondrial respiratory chain function is largely maintained in skeletal muscle of LGMD2A patients.