Alkaptonuria
Syn .: MIM*203500, ochronosis.
Def.: Rare metabolic hereditary disease with autosomal recessive deficiency of homogentyisic acid oxidase (2,5-dioxyphenylacetic acid).
Epid.: Very rare. Frequency – 1: 300. In certain regions, eg in some parts of Slovakia – 000: 1.
Etiol .: Homogentisic acid oxidase deficiency, has a gene locus on chromosome 3q (3q21-q23). In humans, 1890 random mutations associated with the disease have been reported. This leads to the accumulation of homogentyisic acid and its metabolites: phenylalanine and tyrosine. As a result of oxidation of the acid product to acetic acid benzoquinone in the connective tissue and cartilage, deposits of melanin-like, brown or blue-black dye – protectose – accumulate. Urine darkens in air (alkaptonuria) or with the addition of alkali.
The enzyme – homogentyisic acid oxidase – contains SH sulfhydryl groups that are blocked by certain chemicals or drugs: phenol, resorcinol, mepacrine and other antimalarial agents that can cause so-called acquired protection. Exogenous protection, mainly of the cheeks, may result from the excessive use of whitening creams with hydroquinone.
Clin.: In patients with congenital alkaptonuria, the first clinical symptoms appear in the 4th decade of life. The only manifestation of the disease in childhood is a change in the color of the urine or the staining of nappies and linen treated with alkaline pH. The triad of consecutive symptoms is clinically characteristic: alkaptonuria, protection and protective arthropathy.
Skin changes: discoloration, usually in the 4th decade of life; the earliest is the thickening of the cartilages of the auricles with a dark or gray-blue color of the skin. There are disseminated skin discolorations, most pronounced on the cheeks, forehead, tip of the nose, armpits, over the joints, and around the genitals. Discoloration of the eyelid discs shine through the skin with a blue color. Sclerae may also be discolored, usually in the third decade of life, and the mucosa of the cheeks and larynx. There are discoloration of tendons or bones visible through the overlying skin. Earwax and sweat take on a brown or black tint. The nails sometimes turn brown.
Organ lesions: they may affect the middle ear with ossicles and deafness, lead to sclerotic changes in the prostate gland and black kidney stones. Large joints (knee, hip and shoulder) and the spine are affected, causing progressive back pain at the beginning of the 4th decade with progressive stiffness over the next 10 years. There may be acute pain syndromes caused by herniated nuclei and discopathy. Spondylosis lesions affecting the thoracic part can lead to a reduction in height of up to 15 cm. Restricted chest mobility causes symptoms of breathlessness. Increased atherosclerotic changes in old age affect the cardiovascular system, and often the mitral and aortic valves.
DL: Enzymatic and chromatographic tests show homogentisic acid in urine. Urine darkening test showing the presence of homogentisic acid after the addition of NaOH.
Hist.: Deposits of carbon black protective dye are macroscopically visible in the cartilages of intervertebral discs, larynx, trachea and joints, and in tendons. Black staining of connective tissue fibers with methylene blue distinguishes the dye from melanin.
DR: Darkening of nappies during infancy confirms the diagnosis. Joint diseases, symptomatic or exogenous protection, porphyria, myoglobinuria, haematuria.
But: There is no effective treatment. Rheumatological and orthopedic treatment as needed. Cosmetic camouflage.
Alkaptonuria exogenous: Protection of mainly the cheeks may result from the excessive use of whitening creams with hydroquinone.
Symptomatic alkaptonuria: Acquired alkaptonuria after the use of chemicals or drugs: phenol, resorcinol, mepacrine and other antimalarials that inactivate homogentisic acid oxidase.
Lit .: [1] Fernandez-Canon J.M., Grandino B., Beltron- Valero de Barnabe D. i wsp.: The molecular basis of alkaptonuria. Nat Gen 1996, 14; 19-24. [2] O’Brien W.M., La Du B.N., Bunim J.J.: Biochemical, pathologic and clinical aspects of alkaptonuria, ochronosis and ochronotic arthropathy. Review of world literature. Am J Med 1963, 34; 813-38.
Source: A. Kaszuba, Z. Adamski: “Lexicon of dermatology”; XNUMXst edition, Czelej Publishing House