Alkaptonuria (Ochronose) 4/5 (1)

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Definition of alkaptonuria

Alcaptonuria is also called ochronosis and is a rare, inherited (genetic) disease that causes the amino acids phenylalanine and tyrosine not to be broken down. Thus, they accumulate / accumulate in, among other things, articular cartilage and heart valves. The disease, which is very rare, is not covered by newborn screening in Norway (as of 2022). Alcaptonuria is most often detected by pediatricians, but rheumatic symptoms mean that rheumatological assessment may also be relevant in some cases.

Occurrence of alkaptonuria

Alkaptonuri is very rare. The number of new cases per year (incidence) is between 1: 250 000 and 1: 1 000 000, which corresponds to approx. 5-25 cases in Norway. Heredity follows an autosomal recessive pattern.

Symptoms of alkaptonuria

This image is missing alt text; its filename is Alkaptonuri-PMC4707406_SaudiMedJ-36-1486-g001.png
Alkaptonuria. The urine in the glass B has been for 24 hours and has become dark. Alajoulin OA, 2015. Openi. CC BY NC SA 3.0

Most people with alkaptonuria have no childhood symptoms. In the 30s, typical symptoms develop that include noticeable early joint and back pain due to Osteoarthrtitis (Ochronosis) in the hips, knees («osteoarthritis») and in the back (spondylosis). Over time, the back can become crooked and crooked (kyphoscoliosis). Narrowing of the spinal cord is seen in spinal stenosis in old age. Some people experience early symptoms of kidney and gallstones, as well as salivary gland stones with swelling in large salivary glands (parotis, submandibularis).

Already in childhood, one can observe striking brown urine that turns almost black if it stands over time. This can lead to an early diagnosis.

Examinations

Medical history includes typical symptoms as mentioned above.

Clinical At a medical examination, the joints and back are assessed with regard to unusually early osteoarthritis. Late in the course of the disease, tendons, including the Achilles tendon, can be damaged. Also osteoporosis (Osteoporosis) can be developed. Skin, eyes and ears are examined because gray discoloration / pigmentation occurs in skin, but also in eyes (on the sclera) and ear cartilage. The heart can be attacked in the form of heart valve disease (aortic and mitral valves).

Laboratory tests in the form of urine test for homogenetic acid (HGA) is important for the diagnosis. discolored urine is not sufficiently specific. Homogentisic acid for 24 hours urine collection is measured via gas chromatography-mass spectrometry (GC-MS). The amount excreted every day in alkaptonuria / ochronosis is between 1 and 8 grams.

Genetic testing also of close family contributes to mapping.

Imaging detects osteoarthritis with a noticeable amount of calcifications in the joints. Unusual calcium is also seen in the back in the intervertebral discs, which can appear as white on X-ray and CT or as black on DEXA scan (osteoporosis measurement). Ultrasound of the heart (echocardiography / Doppler) can detect heart valve changes and on CT of the heart, the coronary arteries (coronary arteries) are often calcified.

Diagnosis

An early diagnosis is crucial in order to reduce late injuries of the disease. The diagnosis is based on symptoms and examination findings. Urine testing for homogeneous acetic acid is especially crucial along with subsequent genetic testing.

Similar diseases (differential diagnoses) in alkaptonuria

Treatment of alkaptonuria

A diet that reduces the intake of phenylalanine and tyrosine (guidance via a nutritionist) is tried. High doses of ascorbic acid (vitamin C) are used, but on a somewhat uncertain basis.

A newer, promising drug is nitisinone. This has shown a clear effect on the disease by inhibiting the metabolism of tyrosine to homogenic acid.

Prognosis

Pain and reduced quality of life. Often need for joint prostheses. Not shortened service life.

References

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