Three case reports of alkaptonuria, a rare metabolic disease, in two first-degree relatives and one patient
Abstract
Alkaptonuria is a rare hereditary disease, characterized by an abnormal blackish coloration of the urine, dark pigmentation of the connective tissue which is due to a deficiency in homogentisate 1, 2-dioxygenase (HGO), a tyrosine catabolizing enzyme. In this study two-years-old girl, five-year-old boy siblings and 11-month-old boy with alkaptonuria were presented. The diagnosis was confirmed by urinary homogentisic acid (HGA) amount. Normal levels of HGA in urine are 2.4 – 12 ng/ml. In these three cases within urine samples, the level of HGA (2.5-dihydroxyphenylacetic acid) showed an increase of 14, 14, 24 fold, respectively. The treatment focuses upon these aspects: correction of the production of HGA and prevention of complications. For reduction of HGA excretion has been suggested treatment with vitamin C and protein restriction have been proposed. Our patients were showed normal growth and development and no major complications of the disease because of consuming a diet with low protein.
References
- Prasad C, Galbraith PA. Sir Archibald Garrod and Alcaptonuria. Clin Genet 2005; 68: 199-203.
- Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, Anderson PD, Huizing M, Anikster Y, Gerber LH, Gahl WA. Natural history of alkaptonuria. N Engl J Med 2002; 347: 2111-21.
- Lorenzini S, Mannoni A, Selvi E. Alcaptonuria. N Engl J Med 2003; 348:1408.
- Keller JM, Nercessian OA, Jaffe IA. New developments in ochronosis: review of the literature. Rheumatol Int 2005; 25: 81-5.
- Uyguner O, Goicoechea de Jorge E, Cefle A, Baykal T, Kayserili H, Cefle K, Demirkol M, Yuksel-Apak M, Rodriguez de Córdoba S, Wollnik B. Molecular analyses of the HGO gene mutations in Turkish alkaptonuria patients suggest that the R58fs mutation originated from central Asia and was spread throughout Europe and Anatolia by human migrations. J Inherit Metab Dis 2003; 26: 17-23.
- Verma SB. Early detection of alkaptonuria. Indian J Dermatol Venereol Leprol 2005; 71: 189-91.
- Jeucken YM, Visser G, Jaarsma AS, van Spronsen FJ. A child with dark discoloration of urine. Ned Tijdschr Geneeskd 1999;143: 1641-3.
- Morava E, Kosztolányi G, Engelke UF, Wevers RA. Reversal of clinical symptoms and radiographic abnormalities with protein restriction and ascorbic acid in alkaptonuria. Ann Clin Biochem 2003; 40: 108-11.
- Forslind K, Wollheim FA, Akesson B, Rydholm U. Alkaptonuria and ochronosis in three siblings. Ascorbic acid treatment monitored by urinary HGA excretion. Clin Exp Rheumatol 1988; 6: 289-92.
- Wolff JA, Barshop B, Nyhan WL, Leslie J, Seegmiller JE, Gruber H, Garst M, Winter S, Michals K, Matalon R. Effect of ascorbic acid in alkaptonuria alterations in benzoquinone acetic acid and an ontogenic effect in infancy. Pediatr Res 1989; 26: 140-4.
- Mayatepek E, Kahas K, Anninos A, Müler E. Effect of ascorbic acid and low-protein diet in alkaptonuria. Eur J Pediatr 1998; 157: 867-8.
- Suzuki Y, Oda K, Yoshikawa Y, Maeda Y, Suzuki T. A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuria. J Hum Genet 1999; 44: 79-84.
- Suwannarat P, O'Brien K, Perry MB, Sebring N, Bernardini I, Kaiser-Kupfer MI, Rubin BI, Tsilou E, Gerber LH, Gahl WA. Use of nitisinone in patients with alkaptonuria. Metabolism 2005; 54: 719-28.
Abstract
Alkaptonuri, tirozini katalizleyen homogentisat 1, 2-dioxygenase (HGO) enziminin eksikliğine bağlı, bağ dokusunda koyu pigmentasyon artışı ve idrarın siyahımsı anormal renk değişimi ile karakterize kalıtımsal nadir bir hastalıktır. Bu çalışmada, tanıları idrar homogantisik asit miktarı ile doğrulanan, alkaptonurili beş yaşında bir erkek çocuk ve iki yaşındaki kız kardeşi ile akrabaları olmayan 11 aylık bir erkek çocuk hasta sunuldu. Bu üç olgunun idrar örneklerindeki homogentisik asit (HGA) seviyelerinde sırasıyla 14, 14 ve 24 kat artış gösterildi. Hastalığın tedavisi HGA üretiminin düzeltilmesi ve komplikasyonlarından korunma üzerine yoğunlaşmıştır. HGA atılımının azaltılması için C vitamini tedavisi ve diyette protein alımının kısıtlanması önerilmektedir. Hastalarımızın diyetlerindeki düşük protein tüketimi nedeniyle büyümegelişmeleri normaldi ve hastalığın ana komplikasyonları bulunmuyordu
Keywords
References
- Prasad C, Galbraith PA. Sir Archibald Garrod and Alcaptonuria. Clin Genet 2005; 68: 199-203.
- Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, Anderson PD, Huizing M, Anikster Y, Gerber LH, Gahl WA. Natural history of alkaptonuria. N Engl J Med 2002; 347: 2111-21.
- Lorenzini S, Mannoni A, Selvi E. Alcaptonuria. N Engl J Med 2003; 348:1408.
- Keller JM, Nercessian OA, Jaffe IA. New developments in ochronosis: review of the literature. Rheumatol Int 2005; 25: 81-5.
- Uyguner O, Goicoechea de Jorge E, Cefle A, Baykal T, Kayserili H, Cefle K, Demirkol M, Yuksel-Apak M, Rodriguez de Córdoba S, Wollnik B. Molecular analyses of the HGO gene mutations in Turkish alkaptonuria patients suggest that the R58fs mutation originated from central Asia and was spread throughout Europe and Anatolia by human migrations. J Inherit Metab Dis 2003; 26: 17-23.
- Verma SB. Early detection of alkaptonuria. Indian J Dermatol Venereol Leprol 2005; 71: 189-91.
- Jeucken YM, Visser G, Jaarsma AS, van Spronsen FJ. A child with dark discoloration of urine. Ned Tijdschr Geneeskd 1999;143: 1641-3.
- Morava E, Kosztolányi G, Engelke UF, Wevers RA. Reversal of clinical symptoms and radiographic abnormalities with protein restriction and ascorbic acid in alkaptonuria. Ann Clin Biochem 2003; 40: 108-11.
- Forslind K, Wollheim FA, Akesson B, Rydholm U. Alkaptonuria and ochronosis in three siblings. Ascorbic acid treatment monitored by urinary HGA excretion. Clin Exp Rheumatol 1988; 6: 289-92.
- Wolff JA, Barshop B, Nyhan WL, Leslie J, Seegmiller JE, Gruber H, Garst M, Winter S, Michals K, Matalon R. Effect of ascorbic acid in alkaptonuria alterations in benzoquinone acetic acid and an ontogenic effect in infancy. Pediatr Res 1989; 26: 140-4.
- Mayatepek E, Kahas K, Anninos A, Müler E. Effect of ascorbic acid and low-protein diet in alkaptonuria. Eur J Pediatr 1998; 157: 867-8.
- Suzuki Y, Oda K, Yoshikawa Y, Maeda Y, Suzuki T. A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuria. J Hum Genet 1999; 44: 79-84.
- Suwannarat P, O'Brien K, Perry MB, Sebring N, Bernardini I, Kaiser-Kupfer MI, Rubin BI, Tsilou E, Gerber LH, Gahl WA. Use of nitisinone in patients with alkaptonuria. Metabolism 2005; 54: 719-28.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Case Reports |
| Authors | |
| Publication Date | June 11, 2010 |
| Published in Issue | Year 2010Volume: 32 Issue: 2 |