Symptómy choroby


Jedným z hlavných symptómov Alkaptonúrie (AKU) je osteoartritída.

Pri vzorke 20- až 30-ročných pacientov pozorujeme ako jeden z prvých príznakov bolesť kĺbov, najmä v zadnej časti a v oblasti chrbtice. Je to výsledkom procesu nazývaného ochronóza, ktorý nastáva ukladaním kyseliny homogentisovej (HGA) v spojivovom tkanive tela (akým sú napríklad kosti, chrupavky a koža). Ochronóza je jedným z hlavných identifikátorov alkaptonúrie: pacienti pozorujú čierne bodky v očiach a chrupavky ich uší začínajú hrubnúť a tmavnúť.

HGA attacks the bones and cartilage, turning them black and brittle over time. Joints become less able to cope with activities which put them under strain, with the large weight-bearing joints, such as the knees, shoulders, hips and the spine, the worst-affected. Arthropathy, diseased joints characterised by swelling and enlarged bones, is commonly associated with AKU. Normal wear and tear on the body causes the weakened cartilage to break apart and bones to rub together, which causes painful and debilitating osteoarthritis.

Alkaptonuria patients suffer intense joint pain and decreased mobility. Many will have surgery to replace black and brittle joints, and sometimes patients end up wheelchair-bound. In general, patients start complaining of back pain in their 20s and 30s, and knee pain in their 40s. However, the onset of osteoarthritis can vary greatly from one patient to the next. Hip and shoulder pain often occurs later by their 50s.

Many people have at least one joint replaced by the time they reach 55. It is common for AKU patients to have far more than one joint replacement. Many AKU patients have between five and ten joint replacements in their lifetime, sometimes more.

Srdcové komplikácie

Homogentisic acid (HGA) can accumulate in the blood vessels (veins and arteries) and inside the heart. The aortic and mitral valves, which separate the chambers of the heart are usually the most affected. HGA attacks the vessels and valves of the heart, causing them to harden.

A build-up of HGA causes the vessels and valves to harden. They then become blackened, brittle and less effective at managing the flow of blood around the body. This can cause increased blood pressure and it is thought to lead to heart disease. Many AKU patients have to have a heart valve replacement within their lifetime. Surgeons have reported that it’s a difficult surgery to perform, due to hard and brittle cartilage surrounding the heart. Is it thought that, due to the effects of alkaptonuria, there is a risk that debris can fall into the blood stream and increase a patient’s risk of stroke.

Our group based at the US National Institutes of Health (NIH) are carrying out research into the potential heart complications caused by AKU. There seems to have been an increase in AKU patients reporting problems with their heart, blood pressure and cholesterol. It is the only symptom of alkaptonuria that has the potential to be fatal.

Some health professionals believe the link between heart problems and AKU may have been previously underestimated. However, involvement of the heart is still believed to be an uncommon symptom, usually occurring later in life.

Čierny moč

Čierny moč je jedným z charakteristických symptómov alkaptonúrie (AKU).

V prípade ak je moč alkaptonurických pacientov vystavený otvorenému prostrediu, tmavne a napokon sa stáva čiernym. Dĺžka času potrebná na zmenu farby môže byť v prípade jednotlivých pacientov rôzna, od menej ako hodiny až do približne dvoch dní, avšak je pozorovateľná u takmer všetkých AKU pacientov. Existujú však záznamy o malom počte AKU pacientov, ktorí nemajú čierny moč.

Čierny moč nespôsobuje zdravotné problémy, je však využívaný ako diagnostický nástroj. Je zároveň jedným z prvých symptómov Alkaptonúrie pozorovateľný u mladých pacientov, skorá diagnóza je možná aj v prípade moču obsiahnutého v plienkach. Obsiahnutá kyselina homogentisová (HGA), ktorá spôsobuje čierny moč, môže zároveň ovplyvňovať mechúr, prostatu a spôsobovať obličkové kamene.

Čierne škvrny objavujúce sa v očiach

Veľa pacientov s Alkaptonúriou (AKU) sa vyznačuje čiernymi bodkami v očnom bielku (beľmo), zapríčinených procesom nazývaným ochronóza. Čierne bodky v oku neovplyvňujú videnie.

Black spots in the eyes are not present from birth but develop as the disease progresses. Patients usually begin to develop black spots in their eyes during their 40s, which slightly increase in size as they get older.

Although this can appear to be a serious symptom of AKU, it does not cause any pain or other complications. Unfortunately, there is no clinically proven treatment available to prevent or reverse this symptom.

Strata zafarbenia uší

The ears of nearly all alkaptonuria (AKU) patients turn a darkened, blue-black colour. This is due to homogentisic acid (HGA) attaching to cartilage within the ear.

Rovnako ako čierne bodky v očiach, this can appear to be a serious symptom of AKU, but it does not cause any pain or other complications.

Alkaptonuria patients also produce black ear wax, which is due to the accumulation of HGA. This is a similar process to the one which causes other symptoms, such as black urine or black sweat.

There is no clinically proven treatment available to prevent or reverse this symptom. However, a small number of patients have reported that the discolouration of their ears has reduced when taking nitisinone. Reports such as these are being monitored at the National AKU Centre during yearly visits, and our clinical trials are looking at the effectiveness of nitisinone as a treatment for AKU.

Ďalšie symptómy

Alkaptonúria (AKU) môže takisto ovplyvniť niekoľko ďalších oblastí ľudského tela.

Obličkové kamene

Some homogentisic acid (HGA) is eliminated from the body in urine, but as it passes through the genitourinary tract, it can increase the likelihood of developing stones. This can be seen as kidney or bladder stones in both male and female patients and as prostate stones in males. Stones are a fairly common symptom of AKU, but they don’t have a serious effect on health. They can be painful, but most pass out of the body naturally. Occasionally larger stones can be removed by simple operations.

Dýchací aparát (orgány a prvky zapojené do dýchania)

HGA is known to be deposited on the cartilage of the voice box (larynx), the windpipe (trachea) and the airways to the lungs (bronchi). While this causes a black discolouration, it is not thought to cause any serious medical problems.

Zmeny na koži

Effects on the skin are most noticeable in areas exposed to the sun and where sweat glands are located. Skin takes on a blue-black speckled discolouration. Sweat can stain clothes brown. Pigmentation of the skin is more visible in some patients than others. It is often first seen in the ear lobe. It can also be seen in the bridge of the nose, cheeks, hands and skin overlying tendons. The age at which these effects become noticeable varies according to the individual.

Ostatné systémy ľudského tela

The teeth, central nervous system (brain and spinal cord) and endocrine organs (which make hormones) may also be affected. The symptoms of AKU vary from one person to another. Those described here do not necessarily apply to every patient, but generally will be seen to some degree.