Ochronosis is a congenital metabolic disease whose harmful effects on health usually only become noticeable in middle age. Due to the lack of symptoms at first, the metabolic disease is rarely diagnosed in infancy.
What is ochronosis?
The medical term ochronosis is derived from the color ochre, a shade of yellow. In the course of the ochronosis disease, yellowish to brownish discolorations are typically visible on certain body tissues. These brown spots are caused by an increased accumulation of colored pigments in the interstitial tissue. See aviationopedia for NPC Explanations.
The connective tissue of the cartilage and the skin are particularly affected by ochronosis. The disease has an incidence of 1 in 250,000, which means that on average one in 250,000 people will develop it. However, this does not apply globally, but refers to certain ethnic groups and areas.
Ochronosis is more common in Slovakia and the Dominican Republic than in other parts of the world. This fact is considered to be certain, but it is still not known why ochronosis occurs more frequently in these countries than elsewhere.
Strictly speaking, the symptoms of ochronosis, which describes the yellow discoloration of connective tissue, are only the symptom of a causative disease, alkaptonuria. Patients diagnosed with ochronosis also have alkaptonuria, the root cause.
Alkaptonuria is a so-called autosomal recessive genetic disease. As a result, the tyrosine metabolism is disrupted 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 work properly.
There is a deficiency of this enzyme, but it is not completely absent, as is the case with many other inherited enzyme defects. The absence of the enzyme leads to an accumulation of homogentisic acid in the body’s connective tissue. This chemical compound is initially colorless, but as it progresses it undergoes polymerization and oxidation.
Only then does the yellowish-brownish color pigment typical of ochronosis develop. The particular form of exogenous ochronosis must be distinguished from that caused by alkaptonuria. In the tropics, hydroquinone is occasionally used for hyperpigmentation; this toxic-reducing agent can also trigger ochronosis of the connective tissue.
Symptoms, Ailments & Signs
In ochronosis due to alkaptonuria, the deposition of homogentisic acid begins in early childhood. 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 illness, only later does the typical yellowish-brownish discoloration appear from around middle age due to oxidation and polymerisation.
Unfortunately, ochronosis is not just a cosmetic problem, but gradually leads 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, and the heart valves can also be damaged by the storage of homogentisic acid in such a way that their functionality is significantly restricted.
The only and first diagnostic clue in children and infants can be very dark-colored urine, which cannot be attributed to a lack of fluid intake. This dark-colored urine is particularly easy to see on diapers or white underwear.
Diagnosis & course of disease
From the age of 30 to 40, the symptoms and complaints increase noticeably. The skin and also the sclera on the eye can gradually discolour. There are bluish, but also yellowish to deep brownish discolorations. The joints that are subjected to the most stress, such as knee joints or hips, are particularly affected by pain.
These joint problems, which also frequently occur in the shoulder joints and in the lower part of the spine, are chronically progressive. 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 problems.
Since the symptoms in the lower part of the back, i.e. in the lumbar spine, also occur at night, the differential diagnosis to rule out Bechterew’s disease is also important. In advanced stages, ochronosis can lead to cardiac dysfunction, kidney stones, and even fractures.
In most cases, early diagnosis and treatment of ochronosis is not possible 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 reduced self-esteem.
Most of those affected are ashamed of these symptoms, which often leads to social problems or depression. It also causes damage to the individual muscles or joints. Especially in the heart, ochronosis can lead to serious complications and, in the worst case, to the death of the affected person. The urine of those affected is also usually dark in color due to ochronosis.
This leads to general fatigue and a significantly reduced resilience. There is often pain in the hips or joints, which leads to significant limitations in movement. Treatment of ochronosis can be done with the help of medication. As a rule, there are no special complications. However, the further course of the disease depends heavily 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 not diagnosed until middle age. Adults should always take part in the preventive medical check-ups that are offered. This enables early detection of numerous diseases and can be advantageous for the fastest possible intervention in the event of gradual changes in health. If you are restricted in your mobility, you should consult a doctor. If everyday obligations can no longer be fulfilled without symptoms or if unusual irregularities occur when performing sporting activities, a doctor is needed.
If the limitations are greater than the natural aging process intends, there is a need for action. Movement disorders, changes in skin appearance and general malaise should be examined. Discolouration is characteristic of ochronosis. In the case of yellowish-brown tones on the skin or in the urine, a doctor’s visit should be initiated as soon as possible. In some cases, there is also discoloration of the sweat secretions.
Abnormalities of the connective tissue, circulatory disorders or a decrease in resilience are further signs of an existing disease. A doctor should be consulted because ochronosis causes cell damage and has a progressive course of the disease. 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 advisable.
Treatment & Therapy
The diagnosis of ochronosis is made by analyzing the homogentisic acid in the urine. In addition, the genetic disorder responsible for alkaptonuria can also be unequivocally demonstrated using 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.
Because only then can targeted treatments and therapies be initiated as early as possible and destruction of the cartilage or connective tissue prevented or at least reduced. In addition to symptomatic therapy for pain relief, dietary intake of the two amino acids phenylalanine and tyrosine has proven itself.
Outlook & Forecast
Ochronosis is an incurable, chronic disease. It usually causes severe physical disorders and defects. Patients suffer from defects in the heart valves, stiffening of the spine or kidney stones. As a result, in many cases the patients are unable to move independently. The severe pain in the limbs often leads to side effects in the patient, which must be included in the prognosis. The symptoms have a strong negative effect on well-being. The patients are dependent on drug treatment with painkillers and have to be treated as inpatients. The quality of life is greatly reduced. The disease eventually leads to the total loss of motor functions.
There is no prospect of recovery. The prognosis is usually correspondingly poor. However, individual factors such as the general condition of the patient and the severity of the disease must be taken into account. The prognosis is made by the pediatrician or a specialist. Due to the usually severe course, the parents usually have to 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.
Since alkaptonuria and ochronosis are genetically determined hereditary diseases, direct prophylaxis is not possible. As part of an amniotic fluid examination, amniocentesis, in the early phase of pregnancy, the very rare congenital defect of tyrosine degradation can be detected.
In the case of ochronosis, the options for direct follow-up care are significantly limited in most cases. Those affected should first and foremost consult a doctor very early on with this disease, so that there are no other complications and symptoms. The earlier a doctor is contacted, the better the further course of the disease, so that a doctor should be consulted as early as possible.
Self-healing cannot occur in ochronosis. If the affected person or the children wish to have children, a genetic examination and counseling should be carried out in any case in order to prevent the disease from reoccurring. Most patients with ochronoseua are dependent on an operative intervention, through which many of the symptoms can be alleviated.
The person concerned should definitely rest and rest after such an operation, whereby exertion or stressful and physical activities are to be avoided. Regular check-ups and examinations by a doctor are often necessary after the procedure. If the disease is recognized and treated early on, the life expectancy of the affected person is usually not reduced.
You can do that yourself
Since ochronosis is a congenital disease, it has not yet been possible to treat the condition causally. Therapy focuses on alleviating the symptoms and enabling the patient to lead a relatively symptom-free life. The treatment can be supported by the person concerned with a number of measures.
First of all, dietary measures are recommended. The diet is optimally composed of many amino acids, especially tyrosine and phenylalaline. In general, a healthy and balanced diet with enough fresh vegetables and lean meat should be observed. Sporting activities and physiotherapeutic measures can be used to treat joint damage that has already occurred. Together with the doctor responsible, the patient must draw up a training plan that is optimally adapted to the respective symptoms. It is essential to regularly exercise the affected joints to slow their deterioration.
Further measures depend on which symptoms are added to the characteristic joint disorders. 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 also represents a psychological burden, accompanying therapeutic advice must be obtained. Equally important is the support of family and friends.