Oculocutaneous albinism type 2 is the most common variant of albinism worldwide, affecting the skin, hair, and eyes. The phenotypic appearance of the disease covers a wide range, from barely visible to complete albinism. Equally variable are the visual impairments associated with this type of albinism.
What is oculocutaneous albinism type 2?
The main phenotypic symptom accompanying all forms of oculocutaneous albinism type 2 (OCA2) is largely unpigmented skin. Another feature is hair color, which in some cases may be blond or even brown, referred to as brown OCA. Because affected individuals may also have blond hair, the disease is often not recognized in residents of Scandinavia. This is because the skin color does not differ from that of particularly fair-skinned Scandinavians, especially since the iris of the eyes can also take on a brown to blue-green coloration. The visual defects often associated with OCA2 consist in a limited visual acuity and a very strong sensitivity to light. The loss of much of the pigmentation is attributed to a defectively encoded membrane protein of melanosomes. Melanosomes, like lysosomes, are functional organelles in pigment cells. They synthesize melanin in the melanocytes of the epidermis and in the pigment epithelial cells of the iris. Because of a genetic defect, there is a dysfunction of the enzyme tyrosinase, which is involved in the formation of melanin from tyrosine.
Causes
The skin pigment melanin is produced by a specific type of skin cell, the melanocyte. These cells are located in the basal layer of the epidermis. The pigment is formed from tyrosine in special cell organelles called melanosomes and is released to horny cells (keratinocytes), which migrate to the surface of the skin within 28 days and are exfoliated as tiny scales. The formation of melanin from tyrosine in the melanosomes requires the enzyme tyrosinase, which is produced in the endoplasmic reticulum. To cross the membrane enclosing the melanosome, tyrosinase relies on a special transport protein called P protein. The P protein is encoded by the so-called P gene, which is located on the long arm of chromosome 15 (gene locus 15q11-13). A mutation in intron 1 of the P-gene leads to a faulty coding of the P-protein with an extensive loss of function. As a result, the tyrosinase, which is urgently needed in melanosomes, cannot cross their membrane and is instead excreted or metabolized beforehand. Ultimately, the incorrectly encoded P protein results in insufficient melanin production. OCA2 is inherited in an autosomal recessive manner. This means that both parents must have the same genetic defect for the disease to occur.
Symptoms, complaints, and signs
The most noticeable symptom that is seen in oculocutaneous albinism type 2 is the decreased endowment of the skin with the pigment melanin. This is not a complete loss of pigment, but a “base pigmentation” remains. This means that those affected have a lighter skin color compared to healthy people. However, this symptom is less noticeable in fair-skinned Scandinavians, especially in winter, so the symptoms may be overlooked in them. Affected individuals often later develop clearly visible pigmented patches on the skin, called nevi. Since OCA2 is not caused by a uniform genetic defect but by different genetic mutations, the occurrence of symptoms and signs also varies. Most importantly, visual impairment varies in severity.
Diagnosis and course of the disease
Oculocutaneous albinism type 2 is caused exclusively by mutations of the P gene. No other causes such as contact with pollutants, infections suffered, or unusual psychosocial problems can be considered. The course of the disease requires certain protective measures against direct sunlight, both for the eyes and for the skin. The eyes are usually very sensitive to sunlight, and the skin is insufficiently protected against sunburn by melanin. Ultimately, a clear and reliable diagnosis can only be made by molecular genetic testing.
Complications
In oculocutaneous albinism type 2, the pigment melanin in the skin is absent, so skin protection is lost. Therefore, the only way to avoid complications is to provide adequate sun protection for the eyes and skin. Thus, sunglasses should be worn at all times to protect the eyes. Otherwise, there is a dramatic reduction in visual acuity, which can lead to blindness. Sometimes eye tremor or strabismus (squinting) is also observed. In addition to eye protection, pre-existing vision problems must be compensated with special glasses or contact lenses. To prevent blindness, in some cases the lens must be surgically replaced. To protect the skin, sunscreens that have a strong UV filter should always be used. Otherwise, there is a great risk of developing skin cancer. In most cases, multiple basaliomas (white skin cancer) develop. These are semi-malignant skin tumors that do not lead to death, but in their vicinity to the complete destruction of the tissue. As the second most common form of skin cancer, spinalioma, a so-called squamous cell carcinoma, can develop. In addition to severe destruction of the tissue, metastases also form here in distant regions of the body. However, the most dangerous is the so-called melanoma (black skin cancer), which forms metastases very quickly and can affect all organs of the body. Patients with oculocutaneous albinism type 2 should therefore be examined regularly for skin tumors.
When should you see a doctor?
Oculocutaneous albinism type 2 is not in itself a pigmentary disorder requiring treatment. In Scandinavia, where fair skin and blond hair are normal, oculocutaneous albinism type 2 is often not even recognized. But the associated sensitivity to light and the risk of developing skin cancer from UV rays are risks that necessitate regular visits to the doctor. Eye diseases associated with albinism may also require a visit to the ophthalmologist. Protection of pigment-less skin and sensitive eyes is an urgent measure when oculocutaneous albinism type 2 has been diagnosed. Sunglasses should be worn at all times, even on cloudy days. Otherwise, there is a risk of blindness. Sunscreens should have the strongest sun protection factor. A physician should regularly examine the skin for nevi or signs of skin cancer. There are clustered basal cell carcinomas in oculocutaneous albinism type 2.
Treatment and therapy
Treatment options for OCA2 are essentially exhausted to treatment of symptoms and protective measures suitable to effectively protect the eyes and skin from the UV component of sunlight. Sunscreen and sunglasses should be able to block or filter out a sufficiently high UV component of sunlight. For long stays in tropical and subtropical countries, clothing that provides designated UV protection is recommended. Special attention should be paid to the eyes, because in many cases the fovea centralis, the tiny zone of sharpest vision, suffers from the lack of melanin, which can lead to impaired visual acuity. If premature lens opacification, which resembles cataracts, occurs due to insufficient UV protection of the eyes, surgical replacement of the lens can restore vision.
Outlook and prognosis
Oculocutaneous albinism type 2 is not a life-threatening condition, but it is often a life-impacting inherited pigmentation disorder. This represents the more common form of albinism. Affected individuals are completely white-skinned. They have white-blond hair because of a disorder of melanin formation, melanosome formation or transfers of melanosomes. Affected individuals are more susceptible to skin cancers because of the lack of pigmentation in the skin. Otherwise, affected individuals often suffer lifelong stigma because of their light hair and skin color, and increased sensitivity to light. The degree of social exclusion depends on the region in which they live. The level of information about albinism also plays a role. In some tribes in Africa, the inheritance rate is significantly increased. There, albinism is not considered uncommon. The prevalence of oculocutaneous albinism type 2 can be 1:1,500 in some tribes. This compares to a prevalence of 1:15,000 or 1:20,000 births in other countries.Oculocutaneous albinism type 2 is common among the Hopi or Navaho Indians. In some albinos in Africa, the skin is dotted with dark brown patches called nevi. Overall, the prognosis is good. Such people can live to a ripe old age if they protect themselves from UV radiation. The prognosis becomes worse if there is concomitant Prader-Willi syndrome, or Angelman syndrome.
Prevention
Preventive measures that could prevent autosomal recessive oculocutaneous albinism type 2 are nonexistent. However, preventive measures that mitigate the risk of developing sequelae are recommended. First and foremost, because of the increased risk of skin cancer from sun exposure, regular dermatologic examination of the skin is indicated. Regular examinations increase the chance that developing skin cancer can be detected at an early stage and treated. Equally important is effective UV protection for the eyes to minimize the risk of developing cataracts at an early age.
Follow-up
Basically, follow-up care is necessary to prevent the disease from recurring in the future. Oculocutaneous albinism is not considered curable. Therefore, medical management cannot be the goal. Instead, appropriate aftercare should help the patient to cope with everyday life and prevent complications. In the case of acute symptoms, those affected should consult a physician. Regular examinations are rather the exception with albinism. Already at the time of diagnosis, patients receive comprehensive information about the effects of albinism. Appropriate skin protection is considered a preventive measure for aftercare. Affected persons must avoid direct sunlight. UV radiation is highest, especially at midday, and sunscreen with a high sun protection factor is strongly recommended. People suffering from albinism often also suffer from impaired vision. Here, glasses can bring relief. A very light and pale skin is considered characteristic and a psychological aftercare is therefore advisable. Young sufferers in particular often find their appearance very distressing. Ostracism from peers due to the difference occurs again and again. Some patients also complain about disadvantages in the workplace. Thanks to psychological therapy, anxiety disorders and depression can be prevented at an early stage. Such therapy can be ordered by a doctor.
What you can do yourself
So far, there are no adequate treatment methods, which is why it is mainly the affected person who must take action. This includes the observation of the skin for the smallest changes as well as a regular dermatological examination by a specialist. In this way, possible skin cancer can be detected at an early stage. The earlier this happens, the more effective and less invasive the subsequent treatment. Since fair skin reacts very sensitively to sunlight, suitable sun protection must be consistently applied on a daily basis throughout the year. This can be done in a variety of ways and depends largely on the current sensitivity of the skin. For all skin areas that are permanently exposed to daylight, such as the face, neck and hands, sunscreen with a sun protection factor of 50 or higher is recommended from the pharmacy. In order to protect the eyes and lips sufficiently, it is essential to use a UV filter in sunglasses and lip balms. A few points must also be taken into account when it comes to clothing. Although every piece of clothing protects the skin it covers from UV radiation, the density of the fabric determines the extent of this protection. Particularly tightly woven clothing or UV-protective clothing offers the greatest possible protection. Of course, appropriate headgear should not be forgotten. In everyday life, products such as UV-curing nail polish should be avoided, as should visits to a conventional solarium.