eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Alkaptonuria: Differential Diagnoses & Workup

Author: Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Contributor Information and Disclosures

Updated: Apr 27, 2009

Differential Diagnoses

Mitral Valve Insufficiency
Porphyria, Acute

Other Problems to Be Considered

Aortic stenosis, rheumatic
Osteoarthritis
Mitral stenosis, rheumatic

Workup

Laboratory Studies

  • In patients with alkaptonuria, homogentisic acid can be identified in urine using gas chromatography – mass spectroscopy. Spectrophotometric quantitation shows 2 orders of magnitude elevations above normal.
  • Because many patients present without dark urine, looking for homogentisate in all patients with radiographic evidence of osteoarthritis may be advisable.
  • After DNA extraction from whole blood, screening for mutations can be performed with polymerase chain reaction (PCR) technique.

Imaging Studies

  • Spinal radiography reveals disk degeneration combined with dense calcification, particularly in the lumbar area.
  • Chest radiography is advised to assess for possible involvement of aortic or mitral valves.
  • In affected individuals older than 55 years, CT scanning may provide evidence of coronary artery calcifications.

Other Tests

  • Electrocardiography may be advisable, with particular attention directed at any signs of myocardial insufficiency.

Procedures

  • Other studies and procedures should be directed at the joint disease itself.
  • Joint replacements may become necessary in severely affected larger joints.

Histologic Findings

  • In association with the gross visual finding of black-stained cartilage in various areas of the body (eg, larynx, costochondral junctions, trachea), microscopic examination reveals pigment deposition within and outside cells in these tissues.
  • No specific stain is available to distinguish homogentisate-derived pigment from melanin, and the 2 compounds have similar solubility characteristics.

More on Alkaptonuria

Overview: Alkaptonuria
Differential Diagnoses & Workup: Alkaptonuria
Treatment & Medication: Alkaptonuria
Follow-up: Alkaptonuria
Multimedia: Alkaptonuria
References
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References

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

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

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

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

  5. 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. Dec 1998;21(8):791-8. [Medline].

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

  7. Fisher AA, Davis MW. Alkaptonuric ochronosis with aortic valve and joint replacements and femoral fracture: a case report and literature review. Clin Med Res. Nov 2004;2(4):209-15. [Medline].

  8. Keller JM, Macaulay W, Nercessian OA, Jaffe IA. New developments in ochronosis: review of the literature. Rheumatol Int. Mar 2005;25(2):81-5. [Medline].

  9. Levine HD, Parisi AF, Holdsworth DE, Cohn LH. Aortic valve replacement for ochronosis of the aortic valve. Chest. Oct 1978;74(4):466-7. [Medline].

  10. Lorenzini S, Mannoni A, Selvi E. Alkaptonuria. N Engl J Med. Apr 3 2003;348(14):1408; author reply 1408. [Medline].

  11. Mayatepek E, Kallas K, Anninos A, Muller E. Effects of ascorbic acid and low-protein diet in alkaptonuria. Eur J Pediatr. Oct 1998;157(10):867-8. [Medline].

  12. 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.

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

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

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

  16. 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].

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

  18. Wolff JA, Barshop B, Nyhan WL, et al. Effects of ascorbic acid in alkaptonuria: alterations in benzoquinone acetic acid and an ontogenic effect in infancy. Pediatr Res. Aug 1989;26(2):140-4. [Medline].

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Further Reading

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Keywords

alkaptonuria, ochronosis, alcaptonuria, homogentisuria, dark urine, inborn error of metabolism, IEM, Croonian lectures, abnormal intermediate, homogentisic acid oxidase, homogentisate, vitamin C, arthritis, osteoarthritis, rheumatoid arthritis, ankylosis, dark stained diapers, coronary artery disease, myocardial infarction, phenylketonuria, treatment, diagnosis, joint effusion, aortic valvulitis, mitral valvulitis

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Contributor Information and Disclosures

Author

Karl S Roth, MD, 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 Clinical 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, and Southern Society for Pediatric Research
Disclosure: MDS Pharma Salary Employment

Medical Editor

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 Research, and College of American Pathologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Leonard G Feld, MD, PhD, MMM, FAAP, Sara H Bissell and Howard C Bissell Endowed Chair in Pediatrics, Chief Medical Officer, Levine Children's Hospital, Carolinas Medical Center
Leonard G Feld, MD, PhD, MMM, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, and Juvenile Diabetes Foundation International
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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