Alkaptonuria is an uncommon heritable disorder caused by a gene mutation. It is of historical significance as one of the first so-called 'inborn errors of metabolism' when it was described by the British physician Sir Archibald Garrod in 1902. It is also historically significant for it was another British physician, William Bateman, who suggested to Garrod that his family was an example of a pattern of human disease transmission called autosomal recessive.
Connective tissue throughout the body (as in tendons, and ligaments) is damaged by the cumulative deposition of a metabolic by-product (homogentisic acid or HGA) and becomes brittle and weak. This tissue is also stained by HGA which may be apparent under the arm pits, in the nail beds, the external ears, the forehead, inside the mouth, the white part of the eyes, and in the genital areas. Dark perspiration may cause stained clothing.
The most disabling and painful symptoms result from the degeneration of joint cartilage, especially in the spine and large joints such as knees, shoulders, and hips. These symptoms usually become significant in patients during their 30s and 40s and may require surgical repairs such as joint replacements in the next decade or two. Some people form kidney stones and develop symptoms of damaged heart valves.
This is an autosomal recessive condition in which affected individuals receive one mutation from each parent. Individuals such as the parents with a single copy of the mutation (carriers) do not have symptoms. Couples in which both parents are carriers transfer a 25% risk for alkaptonuria to each child.
Many individuals are diagnosed during infancy or early childhood when parents note stained diapers because darkening of the urine on exposure to the air is a prominent symptom. Staining of connective tissue may also be evident as darkening of the white part of the eye and in the ears. In others the diagnosis is not made until much later in life when joint disease leads to pain and limitation of motion. Degeneration of the disks between the vertebrae of the spinal column can lead to shortening of stature and abnormal curvature of the spine. Heart valves such as those of the aorta can malfunction due to stiffness and calcification.
Because of the widespread manifestations, a multidisciplinary approach with orthopedists, ophthalmologists, urologists, and cardiologists is advisable to treat specific affected areas. Heart valve replacement, joint replacement and spinal surgery may be indicated. Urinary stones may require surgical removal. Periodic eye examinations are needed to monitor the level of astigmatism and to check for glaucoma.
Physical therapy might be helpful in some individuals. It is suggested that activities such as contact sports and weight lifting be limited to minimize joint trauma.