Ochronosis is a congenital metabolic disease whose damaging effects on health usually do not become apparent until middle age. Because of the initial lack of symptoms, the metabolic disease is rarely diagnosed in young children.
What is ochronosis?
The medical name ochronosis is derived from the color ochre, a shade of yellow. As ochronosis progresses, yellowish to brownish discolorations are typically visible on certain body tissues. These brownish areas are caused by an increased storage of colored pigments in the intercellular tissue. The connective tissues of the cartilage and skin are particularly affected by ochronosis. The disease has an incidence of 1:250,000, which means that on average one in 250,000 people will develop the disease. However, this does not apply globally, but refers to specific ethnic groups and areas. In Slovakia as well as in the Dominican Republic, ochronosis occurs more frequently than in other parts of the world. This fact is considered to be certain, but it is still not known why ochronosis is more common in these countries than elsewhere.
Causes
Strictly speaking, the disease symptoms of ochronosis, which is used to describe the yellowing of connective tissue components, are only the symptom of a causative disease, alkaptonuria. Patients diagnosed with ochronosis also suffer from alkaptonuria, the actual cause. Alkaptonuria is a so-called autosomal recessive genetic disease. As a result, there is a disturbance in tyrosine metabolism because a certain enzyme, homogentisic acid dioxigenase, is not produced in sufficient quantities. However, without a sufficient presence of this enzyme, certain important metabolic processes cannot take place correctly. This is a deficiency of this enzyme, but it is not completely absent, as is the case with many other congenital enzyme defects. The lack of the enzyme causes an accumulation of homogentisic acid in the connective tissue of the body. This chemical compound is initially colorless, but as it progresses, polymerization and oxidation occur. Only then does the yellowish-brownish color pigment typical of ochronosis develop. This particular form of exogenous ochronosis must be distinguished from one caused by alkaptonuria. In the tropics, hydroquinone is occasionally used for hyperpigmentation; this toxic-reducing agent can also cause ochronosis of the connective tissue.
Symptoms, complaints and signs
In ochronosis due to alkaptonuria, the deposition of homogentisic acid begins in early infancy. Over time, more and more of this substance is deposited in the cartilage of joints and in the connective tissue of the skin. Initially, this does not lead to any symptoms of disease, but only in the further course of life, from about middle age, oxidation and polymerization lead to the typical yellowish-brown discoloration. Unfortunately, ochronosis is not only a cosmetic problem, but leads insidiously to destruction and cell damage. Those affected therefore suffer in particular from painful restrictions in the spine and joints. The connective tissue of vessels, for example the aorta, as well as the heart valves can also be damaged by the storage of homogentisic acid in such a way that their functioning is considerably restricted. The only and first diagnostic indication in children and infants may be a very dark colored urine, which cannot be attributed to a lack of fluid intake. On diapers or white underwear, this dark-colored urine is particularly easy to see.
Diagnosis and course of the disease
From the age of 30 to 40, the symptoms and complaints increase noticeably. The skin and also the sclerae on the eye may gradually change color. Bluish, but also yellowish to deep brownish discolorations occur. The most stressed joints, for example knee joints or hips, are particularly affected by pain. These joint complaints, which also frequently occur in the shoulder joints and in the lower part of the spine, run a chronic-progressive course. If the diagnosis of ochronosis is not recognized or made even in the advanced stage, then the symptoms can hardly be alleviated by conservative measures against joint complaints.Since the complaints in the lower part of the back, i.e. in the lumbar spine, also occur at night, the differential diagnosis to exclude ankylosing spondylitis is also important. In advanced stages, ochronosis can lead to heart dysfunction, kidney stones, and even bone fractures.
Complications
In most cases, early diagnosis and treatment are not possible in ochronosis because the disease is discovered relatively late. In most cases, those affected suffer from discoloration, so that the skin looks yellow or brown. This can also lead to inferiority complexes or a significantly lowered self-esteem. Most of those affected are ashamed of these complaints, so that social discomfort or depression are also common. Damage to individual muscles or joints also occurs. Especially at the heart, ochronosis can lead to serious complications and, in the worst case, even to the death of the affected person. The urine of those affected is also usually darker in color due to ochronosis. There is a general fatigue and a significantly reduced ability to work under pressure. There is often pain at the hips or in the joints and thus significant restrictions in movement. Ochronosis can be treated with the help of medication. As a rule, no particular complications occur. However, the further course of the disease depends strongly on the time of diagnosis, so that a general course cannot usually be predicted.
When should you go to the doctor?
Ochronosis is a disease that is usually diagnosed in middle age. People in adulthood should always participate in the preventive examinations offered. This allows for early detection of numerous diseases and may be beneficial for prompt intervention in the event of gradual changes in health. If there are limitations in the possibilities of movement, a doctor should be consulted. If daily obligations can no longer be fulfilled without discomfort, or if unusual irregularities occur in the performance of sporting activities, a doctor is needed. If the limitations are more severe than the natural aging process, action is required. Disturbances in movement patterns, changes in skin appearance and a general feeling of malaise should be investigated. Discoloration is characteristic of ochronosis. If there are yellowish-brown shades on the skin or in the urine, a visit to the doctor should be initiated as soon as possible. In some cases, there is also discoloration of sweat secretions. Abnormalities of the connective tissue, disturbances of the blood circulation or a decrease of the resilience are further signs of a present disease. A doctor should be consulted, as ochronosis triggers cell damage and has a progressive disease course. Impairments of the muscles, but also psychological irregularities should be discussed with a doctor. If the joints can no longer be moved as usual, there is cause for concern and a visit to the doctor is advised.
Treatment and therapy
Ochronosis is diagnosed by analyzing homogentisic acid in the urine. In addition, the responsible genetic disorder of alkaptonuria can also be detected beyond doubt by molecular biology. If homogentisic acid is present in the urine, it turns deep black after the addition of sodium hydroxide. The diagnosis can therefore be made unequivocally, but this should be done as early as possible, preferably in infancy. Only then can targeted treatments and therapies be initiated as early as possible and destruction of the cartilage or connective tissue be prevented or at least reduced. In addition to symptomatic therapy for pain relief, a dietary supply of the two amino acids phenylalanine and tyrosine has proven effective.
Outlook and prognosis
Ochronosis is an incurable, chronic disease. It usually causes severe physical disorders and defects. Patients suffer from defects of the heart valves, stiffening of the spine or kidney stones, for example. As a result, in many cases patients are unable to move independently. The severe pain in the limbs often leads to concomitant symptoms in the patients, which must be included in the prognosis. The discomfort has a strong negative impact on well-being.Patients are dependent on drug treatment with painkillers and must be treated as inpatients. The quality of life is greatly reduced. The disease eventually leads to total loss of motor functions. There is no prospect of recovery. Accordingly, the prognosis is usually poor. However, individual factors such as the patient’s general condition and the severity of the disease must be taken into account. The prognosis is determined by the pediatrician or a specialist. Due to the usually severe course, parents must usually be offered therapeutic support. Despite a poor prognosis, individual symptoms can be treated well, so that the patient’s quality of life can be restored, at least in the short term.
Prevention
Because alkaptonuria and ochronosis are genetically determined inherited diseases, direct prophylaxis is not possible. Amniocentesis, an amniocentesis performed early in pregnancy, can detect the very rare congenital defect of tyrosine degradation.
Follow-up
In most cases of ochronosis, the options for direct follow-up are significantly limited. Affected individuals should primarily see a physician very early in the course of this disease to avoid other complications and symptoms. The earlier a doctor is consulted, the better the further course of the disease usually is, so that a doctor should be consulted as early as possible. Ochronosis cannot heal itself. If the affected person or the children wish to have children, a genetic examination and counseling should be performed in any case to prevent a recurrence of the disease. Most patients are dependent on surgical intervention for ochronoseua, through which many of the symptoms can be well alleviated. In any case, the affected person should rest and take it easy after such an operation, refraining from exertion or from stressful and physical activities. Regular checks and examinations by a doctor are often still necessary after the procedure. If the disease is detected and treated early, there is usually no reduced life expectancy of the affected person.
What you can do yourself
Because ochronosis is a congenital disease, it is not yet possible to treat the condition causally. Therapy focuses on alleviating the symptoms and allowing the sufferer to live a relatively symptom-free life. The treatment can be supported by the affected person through some measures. First of all, dietary measures are recommended. The diet is optimally composed of many amino acids, especially tyrosine and phenylalaline. In general, attention should be paid to a healthy and balanced diet with sufficient fresh vegetables and lean meat. For the treatment of joint damage that has already occurred, sporting activity and physiotherapeutic measures are recommended. Together with the responsible physician, the affected person must create an exercise plan that is optimally adapted to the respective complaints. It is essential to exercise the affected joints regularly in order to slow down their deterioration. Further measures depend on which symptoms are added to the characteristic joint ailments. For example, functional disorders of the heart or kidney stones must always be treated by a specialist. The most important self-help measure consists of sufficient rest and bed rest. Since ochronosis is also a psychological burden, therapeutic advice must be sought to accompany it. Support from relatives and friends is equally important.
