Medical Care

In infancy, a history of dark-stained diapers should alert the physician to alkaptonuria.^[9]

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.

More recently, use of nitisinone, an inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase, which mediates formation of homogentisic acid, has been reported.^{[10, 11]} Urinary homogentisate excretion was markedly reduced, and safety of prolonged use is no longer an open question.

Surgical Care

Older individuals may require removal of lumbar discs with fusion.

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

Consultations

Consultations may include the following:

Biochemical geneticist
Neurosurgeon
Orthopedist
Cardiologist (older patients)

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.

Medication

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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. [QxMD MEDLINE Link]. [Full Text].
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Häberle J. Suitability of nitisinone for alkaptonuria. Lancet Diabetes Endocrinol. 2020 Sep. 8 (9):732-733. [QxMD MEDLINE Link].
Ranganath LR, Psarelli EE, Arnoux JB, Braconi D,. Efficacy and safety of once-daily nitisinone for patients with alkaptonuria (SONIA 2): an international, multicentre, open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2020 Sep. 8 (9):762-772. [QxMD MEDLINE Link].
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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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