Albinism

What is Albinism?

Albinism, which means “white” in Latin, refers to a collection of hereditary conditions linked to a reduction or absence of melanin, the pigment that gives color to the skin, hair, and eyes. Because of this, individuals with albinism typically have a distinctive pale appearance. The most commonly recognized type of albinism is oculocutaneous albinism (OCA). OCA is caused by genetic defects that affect melanin production and mainly affects the eyes and skin. Depending on the specific variation of OCA, skin symptoms can range considerably in their severity.

A vital role of melanin during pregnancy is to help signal the proper development of eye structures, so problems with melanin can lead to consistent eye-related symptoms in those with OCA. To date, seven types of OCA have been identified, but this discussion of albinism wouldn’t be complete without mentioning a separate type called isolated ocular albinism (OA1), and two syndromic versions, Hermansky-Pudlak syndrome (HPS) and Chediak-Higashi syndrome (CHS).

The syndromic versions of albinism share the same lack of skin and eye pigment as OCA but are caused by different, more far-reaching genetic problems. For instance, mutations linked to HPS result in issues with bleeding, while those linked to CHS increase susceptibility to infections. There are also other conditions that might appear to be albinism due to similar features like abnormal eye movement or generalized lighter skin color. Noteworthy are two syndromes called Angelman (AS) and Prader-Willi (PWS), which show albinism-like traits because they involve the same genes affected in OCA type 2.

What Causes Albinism?

Albinism is due to inherited changes in our genes that cause certain skin cells, called melanocytes, to malfunction. These defective cells cannot effectively produce or spread a pigment called melanin in the skin. What sets albinism apart from conditions like piebaldism and vitiligo is that the number of melanocytes remains the same; they’re just not working properly. The specifics of which gene changes cause each type of albinism are explained further in the “History and Physical” section.

Risk Factors and Frequency for Albinism

Occurrence rates for albinism range from 1 in 17,000 to 1 in 20,000 people overall. About 1 out of 70 people carry a mutation associated with Oculocutaneous Albinism (OCA). Among these mutations, the most common is OCA2, especially in sub-Saharan Africa. This is due to cultural practices that support marriages between close relatives, which increases the occurrence of the recessive trait in families.

The number of cases for each type of albinism varies:

• OCA1: This type of albinism occurs in about 1 in 40,000 people worldwide. It is most common in America and China, accounting for 70% of cases.
• OCA2: This is the most common type of albinism worldwide, with a prevalence of about 1 in 39,000 people. In African Americans, it occurs in about 1 in 10,000 individuals, while in the general American population, the rate is about 1 in 36,000. In sub-Saharan Africa, the prevalence is higher, at about 1 in 3,900.
• OCA3: This type of albinism primarily impacts individuals in southern Africa, with a prevalence of about 1 in 8,500. It is also found in populations in Pakistan, Germany, India, and Japan.
• OCA4: Although it occurs in about 1 in 100,000 people, it makes up 24% of Japanese cases of albinism. It also occurs in populations in Germany, Turkey, India, Korea, China, Denmark, and Morocco.
• OCA5: This is a very rare form of albinism, which has only been reported in a Pakistani family.
• OCA6: This is also very rare, and has been noted in a Chinese family and a man from eastern India.
• OCA7: This is a very rare form, known from one family in the Faroe Islands.
• Hermansky-Pudlak syndrome (HPS): This occurs in about 1 in 500,000 people globally, but is much more common in Puerto Rico, with a prevalence of about 1 in 1,800.
• Chediak-Higashi syndrome (CHS): This is a very rare form of albinism, with fewer than 500 cases reported in the past 20 years.
• Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS): The prevalence of these conditions (AS at 1 in 12,000 to 20,000 and PWS at 1 in 15,000) is higher than the OCA forms. However, only about 1% of AS and PWS patients have the genetic changes causing an OCA2-like presentation.
• Ocular albinism (OA1): The prevalence of this condition is about 1 in 50,000.

Signs and Symptoms of Albinism

Ocular Cutaneous Albinism (OCA), commonly known as albinism, is a condition that affects the amount of pigment in the skin, hair, and eyes. It is categorized differently, depending on the amount of pigmentation and other symptoms present. One type, OCA1A, causes a complete lack of melanin – the pigment that gives color to our skin, hair, and eyes. As a result, people with this type have white skin, hair, eyelashes, and pink eyes. Other types of albinism also affect pigmentation but to a lesser extent, and in these cases, comparing the individual’s pigmentation to that of family members can be useful in diagnosing the condition.

Beyond the skin, albinism also has significant effects on the eyes. People with this condition may experience light sensitivity, discomfort in bright light, certain vision deficiency and lack of a specific reflex in the eye upon examination. Another common feature is an involuntary eye movement disorder that usually starts 1.5 to 2 months after birth and can be an early indicator of visual deficits. Other ocular symptoms can include misalignment of the eyes, reduced depth perception, and pigmentation changes in the iris.

• Photophobia or photodysphoria
• Refractive defects
• Lack of foveal reflex in the eye
• Involuntary eye movement (nystagmus) starting a few months after birth
• Misaligned eyes or disconjugate gaze
• Reduced fine depth perception
• Changes in eye pigmentation

The different forms of albinism have varying characteristics. They range from OCA1, characterized by total absence of melanin, white skin, hair, and light-colored eyes, to other types like OCA2 and OCA3, where skin pigmentation varies from creamy white to brown, and hair color can range from yellow to light brown. Ocular problems like nystagmus and foveal hypoplasia are common across all types. Some forms are accompanied by other health issues, like Hermansky-Pudlak syndrome (HPS) that involves mild to moderate bleeding, lung or kidney abnormalities, and Chediak-Higashi syndrome (CHS) that causes susceptibility to infections and peripheral neuropathy.

Other rare conditions, like Angelman syndrome and Prader-Willi syndrome, show features of albinism but also have additional symptoms like mental retardation and inappropriate laughter in Angelman syndrome, and poor muscle tone and hyperphagia leading to obesity in Prader-Willi syndrome.

Ocular albinism affects only the eyes, and any skin pigmentation difference is subtle and compared to family members. Most female carriers of this type have pigmentary differences in the retina, which aids diagnosis in affected male children and distinguishes OCA1 from OCA2.

Testing for Albinism

Recognizing the symptoms of diseases affecting the eyes early is very important. It can help manage symptoms and maximize a person’s vision, which can impact their safety, learning, self-esteem, and cognitive development. In some conditions such as Ocular Albinism (OCA), symptoms might not be obvious right away. Signs like changes in skin, hair, or eyelashes’ color might go unnoticed, especially in lighter-skinned families.

The pigmentation or coloring of the iris of the eyes may not reach the adult color until a child is six to nine months old, so changes might be overlooked. Often, changes in a child’s eyes grab the attention of caregivers or doctors in the first three to six months. Pediatricians often suspect OCA during the 2 or 4-month baby check-ups.

When there are different signs along with changes in color, like hearing problems, doctors might look into other related conditions or syndromes. It’s important to note if there are other symptoms like frequent infections, bleeding, or cognitive delays to get the right diagnosis.

An eye specialist can help confirm OCA. The doctor will look for specific changes in the eyes like unusual rapid eye movement, sensitivity to light, reduced pigment in iris and retina, change in eye structure, decrease in clarity of sight, misalignment of eyes, or changes in optic nerves. Skin discoloration combined with these signs will lead to diagnosing ocular albinism.

If there’s a discoloration in the skin with a normal eye examination, doctors will consider whether there may be a nutritional or metabolic disorder present. These could include conditions like phenylketonuria, homocystinuria, histidinemia, Menkes syndrome (copper deficiency), and kwashiorkor. In cases where there is hearing loss, Tietz syndrome could be a possibility.

Genetic testing can confirm the diagnosis, but it is often expensive and not done regularly. Doctors can usually diagnose this condition with a thorough eye exam. However, genetic testing can sometimes be useful, like when differentiating OCA1A and OCA1B in infants as they can appear very similar during the first year of life. Genetic testing can also help when family members of patients with albinism want to find out if they carry the trait.

Lastly, it is important to know that there are no specific blood tests or imaging required for diagnosing or managing ocular albinism.

Treatment Options for Albinism

In albinism, life-long sun protection is vital. People should avoid long exposure to UV light sources, like the sun and tanning beds, or meds that enhance sun sensitivity. For any time spent outside, even if brief, sunscreen of SPF 30+ should be applied liberally and frequently (every 2 hours). While there’re no solid studies favoring high SPF, some suggest using SPF 50 or higher. Protective garments and eyewear, hats, UPF-tagged clothes, and UV protective sunglasses can offer extra defense. Bright light sensitivity can be minimized with dark-lens glasses, or brimmed hats if the glasses hamper vision.

Self-checks and being educated about melanoma detection techniques are key. If there are new skin abnormalities, changes in pre-existing lesions, or lesions that are asymmetrical, have irregular borders, varied colors, or are larger than 6mm, a dermatologist should be consulted. Regular, life-long check-ups (once or twice per year) with a dermatologist are critical, especially starting from adolescence as skin cancer may emerge as early as teenage years.

Eye twitching or nystagmus naturally reduces over time. People may learn to adjust their head posture to reach a position where the twitching is least, often termed the nystagmus null point. Eye muscle surgery can help align eyes, improve posture, and enhance vision in severe cases. Optic evaluations should be conducted up to 4 times a year (for 1-2 year-olds), 1-3 times per year (for 3-6 year-olds), annually (for 5-18 year-olds), and every 2-3 years for adults. The aim should be to treat refractive defects with corrective lenses ideally from 4-6 months of age. Despite these measures, normal vision can’t be assured due to irreversible foveal hypoplasia. With age, bifocals and low-vision aids can help, along with teaching aids and special classroom considerations to mitigate educational delays from visual issues.

Genetic consultation can be helpful for parents of albino kids, the patients themselves and their siblings before they start their families. Albinism is a hereditary condition with a 100% chance of passing on the defective gene. Risk analysis can be done with genetic testing of the unaffected partner if the defective gene variant is known. There are varying chances of producing an albino or a carrier offspring depending on the combination of defective and normal genes. Parents must be informed that non-albino siblings have a 67% chance of being carriers before they contemplate having kids.

Regarding therapy, Nitisinone might aid pigmentation in some albinism types according to animal models, while tests are ongoing. Aminoglycosides offer potential, unproven therapy. Despite some reports, L-DOPA did not improve vision in a 45-patient study. Gene therapy delivering a functional copy of the tyrosine gene in patients provides another therapeutic avenue.

What else can Albinism be?

If a patient experiences nystagmus, an eye condition that causes fast, uncontrollable movements of the eyes, doctors would consider possible causes such as:

• OCA syndromes: A group of conditions that can cause changes in skin, hair, and eye color as well as vision problems
• Ocular albinism: A genetic disorder that primarily affects the eyes
• Optic nerve atrophy and hypoplasia: This can cause poor vision, nystagmus, and a pale appearance of the optic nerve
• Inherited retinal dystrophy: A group of inherited eye disorders that can cause vision loss
• FRMD7-related infantile nystagmus syndrome: A genetic disorder that can cause involuntary eye movement and reduced visual clarity
• Aniridia: A rare genetic condition where the iris, the colored part of the eye, is partially or completely missing
• Aland Island eye disease, Cross-McKusick-Breen syndrome, and Achromatopsia are other potential causes, all of which can cause additional eye-related symptoms

Also, if a patient has hypopigmentation, which is a decrease in skin and hair color, doctors would consider conditions such as:

• OCA syndromes
• Hermansky-Pudlak syndrome: A genetic disorder that can cause albinism, lung and bowel diseases, bleeding problems, and weak or absent platelets
• Chediak-Higashi syndrome: A rare condition that affects the immune system
• Angelman syndrome and Prader-Willi syndrome: These are genetic disorders that can cause a range of physical and intellectual disabilities
• Vici syndrome: A disorder that affects many parts of the body and can cause hypopigmentation among many other symptoms
• Waardenburg syndrome type II and Tietz albinism-deafness syndrome: These are other potential causes, each with their own specific set of symptoms
• Griscelli syndrome: Another rare genetic disorder characterized by immune system problems and distinctive hair color

The doctor will investigate these potential causes and carry out necessary tests to arrive at an accurate diagnosis.

What to expect with Albinism

People with non-syndromic OCA, a type of albinism, generally live as long as the average person. However, they do face a higher risk of getting skin cancer. This risk can vary based on how much sun they’re exposed to in their geographical area and certain social and economic factors.

These factors include not having easy access to sunscreen, not knowing how to protect oneself from the sun, cultural clothing practices, not having easy access to healthcare facilities for regular check-ups which could lead to late diagnosis and treatment, and problems with following through or completing treatment.

In areas where poverty is more prevalent, people with albinism may face social stigma. They can also be targets of discrimination, hostility, and even violence. Tragically, there have been instances where people with albinism are murdered for their organs that are sold illegally.

Despite these challenges, it’s important to note that people with albinism have the same intelligence level as the general population. They may experience some delay in vision development, which could affect their education if not addressed early. Besides, issues related to self-perception and social exclusion can lead to feelings of loneliness and depression. Also, they seem to have a higher rate of attention deficit disorder.

Possible Complications When Diagnosed with Albinism

Visual deficits, such as problems with sight, can have major impacts on one’s day-to-day life. Some examples include:

• Work limitations, as certain jobs require good vision
• Difficulties in reading which could lead to delays in education
• An inability to get a driver’s licence due to poor sight

People with Chediak-Higashi syndrome are at a high risk of getting infections.

Individuals with Hermansky-Pudlak syndrome can often have a Bleeding Diathesis, a condition that causes tendency to bleed or bruise easily.

Prolonged exposure to the sun can cause damage to the skin such as Pachydermia (coarse, thick, and rough skin), actinic keratoses, solar lentigines (more common in non-OCA1A albinos), and solar erythema.

Albinism can increase the risk of skin cancers such as basal and squamous cell carcinomas (BCC, SCC). Among albinos, SCC is the most common, making up over 75% of cancer cases, with some diagnoses happening as early as the teenage years. The areas most affected are the head, face, and hands. Albinism can increase the risk of SCC by as much as 1000 times, particularly in the African population. BCC makes up around 24% of cancer cases, with melanoma accounting for about 1%. Despite the higher risk, melanomas are actually quite rare in albinos, and interestingly, they usually occur in areas not typically exposed to sunlight. Health practitioners are therefore advised to be vigilant, as these melanomas are both rare and tend to be colorless in albinos.