Disease

Brief Summary

Oculocutaneous albinism, type 1B (OCA1B) is a genetic disease caused by problems in the gene that makes tyrosine. Tyrosine is an amino acid needed to produce pigment in the skin, hair, and eyes. This disease is inherited in an autosomal recessive manner. The loci for the gene must have both the mutation in order to express such. In the population, the parents of an albino child are usually carriers of the mutated gene but show no signs or symptoms of the condition.

The gene responsible:

Gene - TYR, 606933.0002

Location - 11q14.3

On the molecular basis, the condition is caused by mutation in the tyrosinase gene

Source

Image:

Person affected by albinism

Frequency

It affects 1 in 20,000 people all over the world. This condition varies among the geographical regions and ethnic groups.

Inheritance

The transmission pattern of OCA1B in a family observed was consistent with an autosomal recessive inheritance. In most cases, the parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they do not show signs and symptoms of the condition.

Brief Summary

OCULOCUTANEOUS ALBINISM

History of Disease

According to recorded history, Sir Archibald Edward Garrod was the first to identify this condition in 1908. He observed hypersensitivity to light and eye misalignment among his patients in Africa and was termed ‘albinism’ referring to ‘white African American’. This was classified to be a lack of pigment (melanin) in the color of skin. Until now, this genetic disorder is prominent in the sub-Saharan region of Africa.

History of Disease

Pathogenesis

The yellow mutant form was naturally found in patients with abundant pheomelanin and little eumelanin. Eumelanin is the black or brown pigment that is derived from tyrosine residues. On the other hand, pheomelanin is the red or yellow pigment derived from tyrosine and cystine. Hence, with a relatively greater amount of pheomelanin, the person would tend to have lighter skin. As mentioned previously, a mutation in tyrosinase gene (606933.0002) causes the phenotype.

Oculocutaneous albinism can be classified into tyrosinase-negative or tyrosinase-positive which mainly tells the presence or absence of the enzyme. In this case, type IIB albinism is known to be clinically similar to tyrosinase-positive albinism. The enzyme is present, however, it cannot enter the pigment cells and synthesize melanin.

According to Spritz et al (1989), a pro81-to-leu substitution was found in a patient with the condition. It is said to interfere with the normal folding of the tyrosinase polypeptide. This relates with the aforementioned inability of the enzyme to enter pigment cells.

Source

Image:

Mutation in the MATP gene that results in albinism compared to a normal gene

Symptoms

Eyes

- Decreased iris pigment

- Decreased retinal pigment

- Choroidal vessels visible

- Decreased visual acuity

- Strabismus

- Nystagmus

- High refractive errors (hyperopia, myopia, astigmatism)

- Misrouting of the optic nerves at the chiasm

- Reduced stereoscopic vision

Skin

- White skin at birth

- Decreased skin pigmentation

- Tan with sun exposure (in some patients)

- Pigmented nevi and freckles (sun-exposed areas)

Hair

- White or light yellow hair at birth

- Light blond to golden brown hair with age

Social Concerns

Individuals with this condition are faced with negative social outcomes. Most of the time, they are avoided and rejected. Some of them were even killed because of their physical appearance. This stigma creates an emotional and mental impact especially to albino children. This calls for a reorientation on the perspective on albinism, as well as awareness of their differences.

Treatment

Eye care:

annual eye exam
wearing prescription lenses/sunglasses
vision correction surgery (e.g. Correction of nystagmus in patients)
skin care and prevention of skin cancer
receiving an annual skin assessment
use of sunscreen/ avoiding sun exposure to prevent burns or cancer

Genetic counseling

regular monitoring
genetic advice on proper treatment

Source

Image:

Vision treatment

Clinical Trials

Title:

Vision Response to Dopamine Replacement

Intervention:

Drug: Levodopa/carbidopa

Phase:

Phase 2

Procedure:

In this study the investigators propose that the retina itself in albinism is deficient in dopamine, and vision improvement will occur as a result of improved retinal function in response to the deficient neurotransmitter dopamine. This study has a pretest-posttest design in order to determine if improvement in vision is in response to replacement of deficiency (dopamine). The electroretinography (ERG) testing and optical coherence tomography (OCT) will be critical determinants to confirm vision improvement as a result of improved retinal function, but are not primary outcome data. Main outcome measures will be collected at pre-treatment, 1 month, 3 months, and 4 months. Change in visual acuity as measured in logMAR by Snellen or sweep visual evoked potential (SVEP) after 3 months of treatment is the primary outcome. Patients include OCA1a patients, OCA1b, OCA2, and unclassified Oculocutaneous albinism (OCA). OCA1a patients clinically are known to have the worst vision, and physiologically have the lowest (or absent) levels of tyrosinase function (Dopamine Production). All patients will be treated with Levodopa/carbidopa 4mg/kg/day in three divided doses.

Goals:

The purpose of the study is to evaluate and document physiologic and functional changes in visual performance and retinal function of patients diagnosed with albinism (a dopamine deficiency state) following a trial of oral Levodopa/carbidopa treatment.This study will have an intent to treat goals. Anyone that fits the inclusion criteria for the study will be entered and receive a study drug.

Further details at:

https://clinicaltrials.gov/ct2/show/NCT01663935?cond=Oculocutaneous+Albinism&draw=2&rank=3

Clinical Trials

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