eliglustat-tartrate and Cerebral-Infarction

Topics: Adult; alpha-Galactosidase; Brain; Cerebellum; Cerebral Infarction; Chromosomes, Human, X; Delayed Diagnosis; Fabry Disease; Female; Humans; Inclusion Bodies; Isoenzymes; Kidney; Magnetic Resonance Imaging; Microscopy, Electron; Myocardium; Rare Diseases; Tomography, X-Ray Computed

Fabry disease is a lysosomal storage disorder that is caused by mutations in the gene encoding a-galactosidase A on Xq22.1. Typically hemizygous male patients exhibit classic phenotypes such as angiokeratoma, acroparesthesias, episodic pain "crises," hypohidrosis, and whorl-shaped corneal opacities from childhood. However, during adulthood, they gradually develop kidney failure, heart disease, and strokes resulting in early death between 40 to 50 years of age. However, recent studies have indicated a high prevalence of disabling clinical symptoms in heterozygous females patients. Patients having the cardiac variant of Fabry's disease exhibit only left ventricular hypertrophy, while patients having the renal variant exhibit only kidney failure. Individuals affected by these variants show higher residual enzyme activity of alpha-galactosidase A than individuals affected by the classic form of Fabry's disease due to missense mutations of the GLA gene. The cerebrovascular involvement in Fabry disease is not rare in both adult hemizygotes and heterozygotes. Infarctions caused by the occulsion of small vessels involving mostly the vertebrobasilar region in approximately two-thirds of the cases, and that is associated with the deposition glycoshingolipids including GL-3 in the walls of these vessels. In Caucasian patients, elongated, ectatic, and tortuous vertebral and basilar arteries are frequently observed on MRAs. Life-threatening megadolichobasilar anomaly with thrombosis has been identified in a large Hungarian family in which the family members share L16P mutation. On performing MRI, an increased signal intensity was observed in the pulvinar in T1-weighted images; this is the characteristic so-called "pulvinar sign". Enzyme replacement therapy has been approved in Japan since 2004 and 2007 for agalsidase beta and agalsidase alpha, respectively. This treatment modestly improves the small-fiber neuropathy, hypohidrosis, hypertrophic cardiomyopathy, and stabilizes the renal function in the long term for up to 54 months. However, it has not helped in decreasing the incidence of strokes.

Topics: Adult; alpha-Galactosidase; Cerebral Infarction; Chromosomes, Human, X; Fabry Disease; Female; Genotype; Humans; Isoenzymes; Magnetic Resonance Imaging; Male; Middle Aged; Mutation, Missense

Fabry disease is an X-linked recessive lysosomal storage disorder resulting from the deficiency of alpha-galactosidase. This disease causes endothelial vasculopathy and affects multiple organ systems. Hemizygous male patients represent the classical renal, cardiac and neurological symptoms of disease. Heterozygous female carriers are frequently asymptomatic, but cerebrovascular events in females are as frequent as in males. Even if rarely seen, neurological damage is an important cause of morbidity. Severe neurological signs that are due to multifocal small vessel occlusions may be present without major thrombosis. In this report, we present a 33-year-old female patient with recurrent neurological deficits secondary to multifocal small vessel involvements. The case had previously been misdiagnosed as multiple sclerosis. Cerebral MRI revealed hyperintense lesions located in bilateral thalamus, supratentorial areas, and left cerebellum. Laboratory and radiological investigations were performed for differential diagnosis, but the etiology could not be identified. During follow-up period, skin lesions and proteinuria were detected. The dermatological, neurological, laboratory, and radiological findings were all suggestive of Fabry disease and the diagnosis was confirmed by subsequent enzyme assays. Fabry disease should be considered in young patients with unexplained stroke-like episodes, especially in those who have infarction in the vertebrobasilar arterial system, angiokeratomas, and proteinuria.

Topics: Adult; alpha-Galactosidase; Brain; Cerebellum; Cerebral Infarction; Diagnosis, Differential; Dominance, Cerebral; Fabry Disease; Female; Humans; Isoenzymes; Magnetic Resonance Imaging; Microcirculation; Multiple Sclerosis; Neurologic Examination; Thalamus