Background: Classic Fabry disease, an X-linked recessive lysosomal storage disease due to the deficient activity of α -galactosidase A, typically presents in early childhood with acroparesthesias, angiokeratomas, hyp...Background: Classic Fabry disease, an X-linked recessive lysosomal storage disease due to the deficient activity of α -galactosidase A, typically presents in early childhood with acroparesthesias, angiokeratomas, hypohidrosis, and corneal dystrophy. The neuropathic pain presumably results from glycosphingolipid accumulation in the vascular endothelium and in small-caliber nerve fibers, and is treatable by enzyme replacement therapy. Later-onset variants with residual α -galactosidase A activity lack vascular endothelial involvement and classic symptoms, which lead to the development of cardiac and/or renal disease after the fourth decade of life. Objective: To expand the later-onset Fabry phenotype to include cramp-fasciculation syndrome without small-fiber neuropathy. Methods: A 34- year-old man who presented with chronic exercise-induced pain, fasciculations, and cramps of the feet and legs, and his similarly affected mother, were evaluated. Clinical, biochemical, and molecular studies were performed. Results: Clinical evaluation suggested the diagnosis of Fabry disease, which was confirmed by reduced plasma and leukocyte α -galactosidase A activities (8.8% and 13.4% of normal, respectively) due to a missense A143T mutation. His mother was heterozygous for the A143T mutation. Conclusion: The presentation of cramps and fasciculations without apparent small-fiber neuropathy expands the phenotype of later-onset Fabry disease.展开更多
Background: The variable clinical features of hereditary sensory and autonomi c neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory ne uropathy could be caused by missense mutations of SPTLC1 a...Background: The variable clinical features of hereditary sensory and autonomi c neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory ne uropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be rec ognised as familial. Objective: To screen persons with dominantly inherited HSAN I and others with idiopathic sensory neuropathies for known mutations of SPTLC1 and RAB7. Patients: DNA was examined from well characterised individuals of 25 kindreds with adult onset HSAN I for mutations of SPTLC1 and RAB7; 92 patients w ith idiopathic sensory neuropathy were also screened for known mutations of thes e genes. Results: Of the 25 kindreds, only one had a mutation (SPTLC1 399T→ G). This kindred, and 10 without identified mutations, had prominent mutilating foo t injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity w ith injuries but no weakness, one had restless legs and burning feet, and one ha d dementia with hearing loss. No mutation of RAB7 was found in any of these. No known mutations of SPTLC1 or RAB7 were found in cases of idiopathic sensory neur opathy. Conclusions: Adult onset HSAN I is clinically and genetically heterogene ous and further work is required to identify additional genetic causes. Known SP TLC1 or RAB7 mutations were not found in idiopathic sensory neuropathy.展开更多
文摘Background: Classic Fabry disease, an X-linked recessive lysosomal storage disease due to the deficient activity of α -galactosidase A, typically presents in early childhood with acroparesthesias, angiokeratomas, hypohidrosis, and corneal dystrophy. The neuropathic pain presumably results from glycosphingolipid accumulation in the vascular endothelium and in small-caliber nerve fibers, and is treatable by enzyme replacement therapy. Later-onset variants with residual α -galactosidase A activity lack vascular endothelial involvement and classic symptoms, which lead to the development of cardiac and/or renal disease after the fourth decade of life. Objective: To expand the later-onset Fabry phenotype to include cramp-fasciculation syndrome without small-fiber neuropathy. Methods: A 34- year-old man who presented with chronic exercise-induced pain, fasciculations, and cramps of the feet and legs, and his similarly affected mother, were evaluated. Clinical, biochemical, and molecular studies were performed. Results: Clinical evaluation suggested the diagnosis of Fabry disease, which was confirmed by reduced plasma and leukocyte α -galactosidase A activities (8.8% and 13.4% of normal, respectively) due to a missense A143T mutation. His mother was heterozygous for the A143T mutation. Conclusion: The presentation of cramps and fasciculations without apparent small-fiber neuropathy expands the phenotype of later-onset Fabry disease.
文摘Background: The variable clinical features of hereditary sensory and autonomi c neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory ne uropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be rec ognised as familial. Objective: To screen persons with dominantly inherited HSAN I and others with idiopathic sensory neuropathies for known mutations of SPTLC1 and RAB7. Patients: DNA was examined from well characterised individuals of 25 kindreds with adult onset HSAN I for mutations of SPTLC1 and RAB7; 92 patients w ith idiopathic sensory neuropathy were also screened for known mutations of thes e genes. Results: Of the 25 kindreds, only one had a mutation (SPTLC1 399T→ G). This kindred, and 10 without identified mutations, had prominent mutilating foo t injuries with peroneal weakness. Of the remainder, 12 had foot insensitivity w ith injuries but no weakness, one had restless legs and burning feet, and one ha d dementia with hearing loss. No mutation of RAB7 was found in any of these. No known mutations of SPTLC1 or RAB7 were found in cases of idiopathic sensory neur opathy. Conclusions: Adult onset HSAN I is clinically and genetically heterogene ous and further work is required to identify additional genetic causes. Known SP TLC1 or RAB7 mutations were not found in idiopathic sensory neuropathy.
