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Alkaptonuria Treatment & Management

  • Author: Karl S Roth, MD; Chief Editor: Maria Descartes, MD  more...
 
Updated: Aug 07, 2015
 

Medical Care

In infancy, a history of dark-stained diapers should alert the physician to alkaptonuria.[8]

Infants, young children, and asymptomatic young adults can be evaluated with simple urine testing on an outpatient basis.

Medical therapy is used to ameliorate the rate of pigment deposition. This minimizes articular and cardiovascular complications in later life.

Reduction of phenylalanine and tyrosine has reportedly reduced homogentisic acid excretion. Whether a mild dietary restriction from early in life would avoid or minimize later complications is not known, but such an approach is reasonable.

Vitamin C, as much as 1 g/d, is recommended for older children and adults. The mild antioxidant nature of ascorbic acid helps to retard the process of conversion of homogentisate to the polymeric material that is deposited in cartilaginous tissues.

Limited use of nitisinone, an inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase, which mediates formation of homogentisic acid, has been reported. Urinary homogentisate excretion was markedly reduced, but safety of prolonged use is still an open question.

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Surgical Care

Older individuals may require removal of lumbar discs with fusion.

Hip, shoulder, or knee joint replacement may be necessary.

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Consultations

See the list below:

  • Biochemical geneticist
  • Neurosurgeon
  • Orthopedist
  • Cardiologist (older patients)
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Diet

Reduction of phenylalanine and tyrosine reportedly reduced homogentisic acid excretion in the urine of a child. In an adult, a similar restriction reportedly had no effect on excretion of the abnormal metabolite. Whether a mild dietary restriction from early in life would avoid or minimize later complications is not known, but such an approach is reasonable.

Vitamin C, as much as 1 g/d, is recommended for older children and adults.

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Contributor Information and Disclosures
Author

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

James Bowman, MD Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago

James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Pathology, American Society of Human Genetics, Central Society for Clinical and Translational Research, College of American Pathologists

Disclosure: Nothing to disclose.

References
  1. Garrod AE. The incidence of alkaptonuria: a study in chemical individuality. 1902 [classical article]. Yale J Biol Med. 2002 Jul-Aug. 75(4):221-31. [Medline].

  2. Lodh M, Kerketta JA. Early diagnosis of co-existent ß-thalassemia and alkaptonuria. Indian J Hum Genet. 2013 Apr. 19(2):259-61. [Medline]. [Full Text].

  3. Zatkova A, Sedlackova T, Radvansky J, Polakova H, Nemethova M, Aquaron R, et al. Identification of 11 Novel Homogentisate 1,2 Dioxygenase Variants in Alkaptonuria Patients and Establishment of a Novel LOVD-Based HGD Mutation Database. JIMD Rep. 2012. 4:55-65. [Medline]. [Full Text].

  4. Lindner M, Bertelmann T. On the ocular findings in ochronosis: a systematic review of literature. BMC Ophthalmology. January 2014. 14:12. [Medline].

  5. Lok ZS, Goldstein J, Smith JA. Alkaptonuria-associated aortic stenosis. J Card Surg. 2013 Jul. 28(4):417-20. [Medline].

  6. Oexie K, Engel K, Tinschert S, et al. Three-generational alkaptonuria in a non-consanguineous family. J Inherit Metab Dis. Dec/2008. Epub:Epub.

  7. US Preventive Services Task Force. Screening for phenylketonuria (PKU): US Preventive Services Task Force Reaffirmation recommendation. Ann Fam Med. 2008 Mar-Apr. 6(2):166. [Medline].

  8. Peker E, Yonden Z, Sogut S. From darkening urine to early diagnosis of alkaptonuria. Indian J Dermatol Venereol Leprol. 2008 Nov-Dec. 74(6):700. [Medline].

  9. de Haas V, Carbasius Weber EC, de Klerk JB, et al. The success of dietary protein restriction in alkaptonuria patients is age-dependent. J Inherit Metab Dis. 1998 Dec. 21(8):791-8. [Medline].

  10. Ffolkes LV, Brull D, Krywawych S, Hayward M, Hughes SE. Aortic stenosis in cardiovascular ochronosis. J Clin Pathol. 2007 Jan. 60(1):92-3. [Medline].

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  16. O'Brien W, La Du BN, Bunim JJ. Biochemical, pathological and clinical aspects of alcaptonuria, ochronosis and ochronotic arthropathy: review of the world literature (1584-1962). Am J Med. 1963. 34:813-38.

  17. Perry MB, Suwannarat P, Furst GP, Gahl WA, Gerber LH. Musculoskeletal findings and disability in alkaptonuria. J Rheumatol. 2006 Nov. 33(11):2280-5. [Medline].

  18. Phornphutkul C, Introne WJ, Perry MB, et al. Natural history of alkaptonuria. N Engl J Med. 2002 Dec 26. 347(26):2111-21. [Medline].

  19. Suwannarat P, O'Brien K, Perry MB, et al. Use of nitisinone in patients with alkaptonuria. Metabolism. 2005 Jun. 54(6):719-28. [Medline].

  20. Vavuranakis M, Triantafillidi H, Stefanadis C, Toutouzas P. Aortic stenosis and coronary artery disease caused by alkaptonuria, a rare genetic metabolic syndrome. Cardiology. 1998. 90(4):302-4. [Medline].

  21. Watts RW, Watts RA. Alkaptonuria: a 60-yr follow-up. Rheumatology (Oxford). 2007 Feb. 46(2):358-9. [Medline].

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Upon microscopic examination, amber-colored, oval-shaped structures are detected in the mid-to-upper dermal tissues (hematoxylin and eosin, original magnification X40).
 
 
 
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