Fabry Disease: A Turkish Case with a Novel Mutation and Dermatological Manifestations
Öz
Fabry disease is a rare, X-linked disease, caused by the deficiency of lysosomal α-galactosidase. Clinical fetaures are; acroparesthesia, unexplained fever, hypohidrosis and angiokeratomas. Untreated cases die early from cardiac complications, renal insuffiency or stroke. Currently there is no cure for Fabry disease, enzyme replacement therapy is the only choice in this progressive disease. A 9-year-old boy admitted to the Dermatology Clinic with reddish papular skin lesions, joint pain and anhydrosis. Hystological examination of the skin biopsy revealed angiokeratoma. There was no renal dysfunction or proteinuria. Biochemical confirmation of Fabry disease was made by determining the deficient leukocyte α-galactosidase activity. Subsequently, the patient’s molecular analysis was identified a novel nonsense mutation c. 785G>T in the GLA gene. Enzyme replacement therapy with agalsidase beta was started. He is on enzyme replacement therapy for 8 years, significant improvement was obtained in severity and frequency of pain crisis and fatigue. We report this case to emphasize the importance of early diagnosis of Fabry disease restricted to dermatological findings, especially before renal and cardiac involvement occurs, while enzyme replacement therapy is now available. Also this patient is one of the first Fabry patients under enzyme replacement therapy in Turkey.
Anahtar Kelimeler
Kaynakça
- Kint JA. The enzyme defect in Fabry’s disease. Nature. 1970;227:1173.
- Lidove O, Kaminsky P, Hachulla E, Leguy-Seguin V, Lavigne C, Marie I, et al. Fabry disease ‘The New Great Imposter’: results of the French Observatoire in Internal Medicine Departments (FIMeD). Clin Genet. 2012;81:571-7.
- Desnick RJ, Ioannou YA, Eng CM. α-Galactosidase A deficiency: Fabry disease. Scriver CR, Beaudet AL, Sly WS, Valle D. The Metabolic Bases of Inherited Disease. 8th ed. New York, McGraw-Hill. 2001:3733– 74.
- Ramaswami U, Whybra C, Parini R, Pintos-Morell G, Mehta A, Sunder-Plassmann G, et al. Clinical manifestations of Fabry disease in children: data from the Fabry Outcome Survey. Acta Paediatr 2006;95:86–92.
- MacDermot KD, Holmes A, Miners AH. Anderson- Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J. Med. Genet. 2001;38:750-60.
- MacDermot KD, Holmes A, Miners AH. Anderson- Fabry disease: clinical manifestations and impact of disease in a cohort of 60 obligate carrier females. J. Med.Genet. 2001;38:769-75.
- Massaccesi L, Burlina A, Baquero CJ, Goi G, Burlina AP, Tettamanti G. Whole-blood alpha-D- galactosidase A activity for the identification of Fabry’s patients. Clin Biochem. 2011;44:916-21.
- Weidemann F, Niemann M, Breunig F, Herrmann S, Beer M, Störk S, et al. Long-term effects of enzyme replacement therapy on Fabry cardiomyopathy: evidence for a beter outcome with early treatment. Circulation. 2009;119:524-9.
- Alfadhel M, Sirrs S. Enzyme replacement therapy for Fabry disease: some answers but more questions. Ther Clin Risk Manag. 2011;7:69-82.
- Morrissey RP, Philip KJ, Schwarz ER. Cardiac abnormalities in Anderson-Fabry disease and Fabry’s cardiomyopathy. Cardiovasc J Afr. 2011;22:38-44.
