Genetic counseling is the process of providing individuals Alkaptonuria is inherited in an autosomal recessive manner. – ALKAPTONURIA; AKU – HOMOGENTISIC ACID OXIDASE in the homogentisate 1,2-dioxygenase gene (HGD; ) on chromosome 3q Alkaptonuria is a rare inherited genetic disorder in which the body cannot process the amino acids phenylalanine and tyrosine, which occur in protein.

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GlyArg [ Srsen et al ].

A number sign is used with this entry because alkaptonuria AKU is caused by homozygous or compound heterozygous mutation in the homogentisate 1,2-dioxygenase gene HGD; on chromosome 3q Activities that place significant physical stress to the spine and joints such as high impact sports gentics heavy manual labor should be avoided.

Older individuals may require removal and fusion of lumbar discs.

However, this testing is not required to confirm the diagnosis. Homogentisate 1,2-dioxygenase functions in the metabolism of HGA by catalyzing an oxidative cleavage of the benzene ring to yield maleylacetoacetic acid. Hereditary ochronosis Homogentisic acid oxidase deficiency Prevalence: Evaluation of relatives at risk: We need long-term secure funding to provide you the information that you need at your fingertips.

Cystinuria Hartnup disease Iminoglycinuria Lysinuric protein intolerance Fanconi syndrome: This assigns scores to the presence of particular symptoms and features, such as the presence of eye and skin pigmentation, joint pain, heart problems, and organ stones.

In general, pigmentary changes are observed after age 30 years.

Rare Disease Database

Specialised Social Services Eurordis directory. Alkaptonuria is a rare disease ; it occurs in one genetixspeople, but is more common in Slovakia and the Dominican Republic. Resources RareConnect offers a safe patient-hosted online community for patients and caregivers affected by this rare disease.


Younger individuals with alkaptonuria should be directed toward non-contact and lower-impact sports. Beltran-Valero de Bernabe, D.


For a detailed summary of gene and protein information, see Table AGene. Joint-replacement surgery hip and shoulder is often necessary at a relatively young age. Surveillance for cardiac complications every one to two years is advisable after age 40 years and should include:. In earlier studies, nitisinone was shown to significantly reduce accumulations of homogentisic acid in individuals with alkaptonuria. Joint mobility is usually diminished and fluid buildup in affected joints effusions may also occur.

Areas with increased frequencies of the disorder have been alkaptonura in Slovakia, the Dominican Republic and Germany.

In many individuals, cartilage within the ear may become thickened, irregular and discolored blue, grey or black.

Ankylosis may be present. Orphanet encyclopedia, Last update October Joint disease in alkaptonuria tends to begin earlier and progress more rapidly in males than females. Joint disease appears to start earlier and progress more rapidly in males than in females.


The joint and spinal symptoms associated with alkaptonuria can geneticw symptoms associated with other disorders such as alkqptonuria arthritis, ankylosing spondylitis, and osteoarthritis. No mutational hot spot or founder effect has been identified in the US [ Phornphutkul et al ]. The pain can be severe to the point that interferes with activities of daily living and may affect ability to alkapgonuria. New England Journal of Medicine During infancy, diapers may be stained black from urine exposure to airalthough this is often missed or ignored.

Differential diagnosis Differential diagnosis includes acute intermittent porphyria, rheumatoid arthritis, ankylosing spondylitis see aloaptonuria terms and osteoarthritis. In the case reported by Steinmann et al. Affected individuals eventually develop ochronosis, which is the bluish-black discoloration of connective and other tissue within the body.


Information on current clinical trials is posted on the Internet at www. The defect was narrowed down to homogentisic acid oxidase deficiency in a study published in To establish the extent of disease and needs in an individual diagnosed with alkaptonuria, the following evaluations are recommended:. Over time rarely before adulthoodit eventually changes the color of affected tissue to a slate blue or black. Prevention of Secondary Manifestations Maintaining joint range of motion through moderate non-weight-bearing exercise such as swimming may have beneficial effects.

Retrieved 17 April The chart in the right lower corner indicates the percentual proportion of individual mutation identified in Slovakia out of Slovak AKU chromosomes. Alkaptonuria in the Trencin district of Czechoslovakia.

In addition to cartilage, homogentisic acid accumulates in other connective tissue including tendons and ligaments and even bone.

Alkaptonuria is caused by deficiency of homogentisate 1,2-dioxygenase, an enzyme that converts homogentisic acid HGA to maleylacetoacetic acid in the tyrosine degradation pathway.

Mutations in the HGD gene cause alkaptonuria. Long-term therapy in young patients with alkaptonuria is indicated.

Molecular Genetics of Alkaptonuria

Family members should be referred for genetic counseling. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. Prevalence At least affected individuals have been described in the literature; this is likely an underestimate.