Aysun YAKUT, Mehmet DİKEÇ, Murat TUĞCU, Murat GÜCÜN, Mustafa CANBAKAN, Gülizar ŞAHİN, Gülbüz SEZGİN, Sheyla APAYDIN

Non - Progresif Kronik Böbrek Yetmezliği olan Alkaptonürili Hasta

Alkaptonüri, otozomal resesif geçişli, 1902 yılında Garrod tarafından tanımlanmış, ilk doğumsal metabolik hastalıktır 1 . Oldukça nadirdir, ancak Slovakya ve Dominik Cumhuriyeti gibi ülkelerde daha sık görülür. 3q kromozomunda kodlanmış, tirozin metabolizmasında rol alan Homogentisik Asit Oksidaz HGO geninde mutasyon 1996 yılında tanımlanmış ve şimdiye kadar 40'ın üzerinde mutasyon tespit edilmiştir 2 . HGO enzim yetersizliğine bağlı olarak idrarla atılamayan Homogentisik Asit HGA ve metabolitlerinin kollajenden zengin bağ dokusunda birikmesi ile hastalık belirti verir 3 . Bu oksidasyon ve pigment oluşumu geri dönüşümsüzdür 4 . Bu özelliklere rağmen, beklenen yaşam süresi sağlıklı bireyler kadardır. Tüm vücutta, yaygın, bağ dokusunda koyu renkli pigment birikmesiyle “okronozis” oluşur. Olgu sunumunda; 2002 yılından beri takip ettiğimiz alkaptonürisi olan kronik böbrek yetmezliği KBY , ileri derece demansı, idrar inkontinansı, yaygın kemik ağrıları ve osteoporozu olan 47 yaşında erkek hasta sunulacaktır.

Anahtar Kelimeler:

alkaptonüri, non-progresif böbrek yetmezliği, okronozis, otozomal resesif

Alkaptonuria Patient with Non - Progressive Chronic Kidney Disease

Alkaptonuria, described by Garrotin 1902, is one of the first congenital disorder. It has an autosomal recessive inheritance pattern. It is a very rare disease,but is seen more often in Slovekia and Dominican Rebuplic.The human gene for the disease is coded on chromozome 3q. Mutation in the homogentisic acid oxidase which has a role in tyrosine metabolism has been described in 1996 and up to now, 40 mutations have been described in this gene. Homogentisic acid and oxydase HGO enzyme deficiency causes the accumulation of homogentisic acid and its metabolites in the blood and precipitations in all the connective tisssues of the body. Oxidation and pigment formation process is irreversible. Though life expectancy is similar with healthy individuals. The acumulation and diffuse staining with this brownish black pigment of the all connective tissue of the body and skin, is called ochronosis. Here in,we present a 49y/o male patient who has been under own care since 2012, with chronosis and its clinical course and complications as chronic renal failure, demantia , urinary incontinence and osteoporosis.

Keywords:

alkaptonuria, non-progressif renal failure, ochronosis, autosomal recessive,

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Garrod AE. The incidence of alkaptonuria: a study in chemical individuality. 1902 (classical article ) Yale J Biol Med 2002;75:221-231.
Granadino B, Beltran-Valero de Benabe D, Fernan- dez-Canon JM et Al. The human homogentisate 1,2 dioxygenase gene. Genomics. 1997; 43:115- 122. htpp://dx.doi.org/10.1006/geno.1997.4805 PMid:9244427
Micali G, Stefano AG, Nasca MR, Musumeci ML. A 46 year history of diffuse brownish black pig- mentation. Endogenous ochronosis (alkapto- nuria). Arch Dermatol 1998; 134: 98, 100-101. http://dx.doi.org/10.1001/archderm.134.1.97-a
Janocha S, Wolz W. Srsen S, et al. The human gene for alkaptonuria (AKU) maps to choromao- some 3q. Genomics. 1994: 19: 5-8. Htpp://dx.doi. org/10.1006/geno.1994.1003 PMid:13488201
Keller JM, Macaulay W, Nercessian OA, Jaffe IA. New developments in ochronosiz:review of the literature. Rheumatol Int 2005; 25: 81-85.
O Brien WM, La Du BN, Bunim JJ. Biochemical, pathologic and clinical aspects of alcaptonuria, achronosis and achronotic arthropathy:a re- view of world literature (1584-1962). Am J Med 1963;34: 813-838.
Phorrnphutkul C, Introne WJ, Perry MB, Bernar- dini I, Murphey Md, Fitzpatrick DL, et al. Natı- ral history of alkaptonuria. N Engl J Med 2002; 347:2111-2121.
Goldsmith LA. Cutaneous changes in errors of aminoacidmetabolism: alkaptonuria, In: Fitzpat- rick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, eds. Dermatology in General Medicine 5th ed. New York: McGraw-Hill; 1993. P. 1841-5.
Anikster Y Nyhan WL, Gahl WA. NTBC and alkap- tonuria. Am J Hum Genet 1998;63: 920-921.
La Du BN. Alkaptonuria. In: Scriver CR, Beaudet AL, Sly WS, Vale D, Volglstein B, eds. The Metabo- lic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001.p.2019-2023.
Van offel JF, De Clerck LS, Francx LM, Stevens WJ: The clinical manifestations of ochronosis: a re- view. Acta Clin Belg 1995; 50: 358-362.
Anikster Y, Nyhan WL, Gahl WA: NTBC and alkap- tonuria. Am J Hum Genet 1998; 63: 920-921.
Gutzmer R, et al: Alkaptonuric ochronosis. J Am Dermatol 1997; 37: 305-307.
Gaines JJ, Pai Gm: Cardiovascular ochronosis. Arch Pathol Lab. Med 1987; 111: 991-994.