Alkaptonuria (protection) is a disease in which the body does not break down two amino acids - phenylalanine and tyrosine. As a consequence, the product of their transformation - homogentisic acid - accumulates in the body, leading, inter alia, to to pigmented skin changes, arthritis and tendonitis, and in more serious cases to impaired kidney function or damage to the heart valves. What are the causes and symptoms of alkaptonuria? What is the treatment?
Alkaptonuria(protection) , colloquiallyblack urine disease , is a genetically determined metabolic disease in the course of which the metabolism of two amino acids - phenylalanine and tyrosine is disturbed. The conversion of these compounds is not complete but is stopped at the homogentisic acid stage. As a consequence, this compound accumulates in the body in the form of polymers, which over time lead to a discoloration of the tissues (specialized in protecting diseases) and their damage. Homogentisic acid is most often deposited in the skin, cartilage, fascia, vascular walls, lungs, sclera of the eye, heart valves, dura mater and eardrum.
Alkaptonuria is diagnosed in one in 100-250 thousand. people in the world, but in some areas it is more common, such as in the northwest of Slovakia (where the prevalence is estimated at about 1 in 20,000 people) and in the Dominican Republic, some parts of Jordan and southern India.
In addition, the disease is twice as common in men as in women and is more common in children of related parents.
Alkaptonuria - causes
The disease is caused by a deficiency of an enzyme called homogentisic acid oxidase (HGO), which is involved in the conversion of tyrosine and phenylalanine and is responsible for the breakdown of homogentyisic acid in the body. This deficiency is caused by a mutation in the HDG gene, which contains instructions for the production of the above-mentioned. enzyme.
The disease is inherited in an autosomal recessive manner, i.e. in order for a child to become ill, they must receive one copy of the defective gene from each parent.
Alkaptonuria - symptoms
During childhood, the disease can only manifest itself by changing the color of urine from straw to black or dyeing the color of nappiesand underwear.
The full-blown form of the disease appears only around 30-40 years of age. Then the following appear:
- changes to the skin - yellow, yellow-brown, brown, dark brown or gray-blue spots. They are of different sizes and appear on different areas of the body:
- auricles - dark brown or gray-blue spots appear there very often. Then the accompanying symptom is dark or even black earwax - face - in the area of the zygomatic arch, the skin takes on a brown or dark color - eyelids - black spots appear - limbs - spots appear on the fingers on the side of the hand, on the nail plates, on the soles of the feet - chest - a gray-blue discoloration of the skin is noticeable - under the armpits, around the anus and genitals - there is a brown-olive color - over the tendons, most often around the wrists
A characteristic symptom of alkaptonuria is the change in color of urine to black upon contact with air
- changes in the osteoarticular system
- the so-called protective arthropathy, i.e. degenerative changes in joints, usually affecting large joints (shoulder, hip and knee), which are manifested, among others, by joint pain, morning stiffness, limited mobility of joints and their deformation - feeling of stiffness and pain in the sacro-lumbar region of the spine, which is the result of destruction of discs and calcification of the vertebrae, especially in the lumbar spine - deepening of thoracic kyphosis with simultaneous reduction of lumbar lordosis
- hearing impairment - is the result of homogentisic acid build-up in the eardrum, leading to hearing loss or deafness
- black spots on the eyeball - where the sclera meets the cornea
- nephrolithiasis and renal impairment
- calcifications in coronary arteries and damage to aortic valves
- in men calcifications in the prostate gland
Alkaptonuria - diagnosis
If alkaptonuria is suspected, gas chromatography is performed - a test that detects homogentisic acid in the urine.
In addition, X-rays of the spine (showing disc degeneration and calcifications in the lumbar spine) and joints are necessary.
Alkaptonuria - treatment
Patients can be given high doses of ascorbic acid (vitamin C), which may limit the deposition of protective pigment in the tissues. However, the most recent discovery in the treatment of alkaptonuria is the preparation NTBC, i.e. the 4-hydroxyphenylpyruvic acid dioxygenase inhibitor, whichreduces the production of homogentisic acid.
Until recently, doctors recommended a low-protein diet, which was to inhibit the production of homogentisic acid. However, it turned out that its long-term use did not bring the expected results.
In addition, symptomatic treatment is used, i.e. non-steroidal anti-inflammatory drugs, kinesitherapy, physical therapy, massage.
In very advanced degenerative changes in joints, it may be necessary to insert implants (arthroplasty). A surgeon's intervention may also be necessary in the event of damage to the mitral valve.