Albinism oculocutaneous (overview)E70.3

Group of genetically different, almost exclusively autosomal-recessive inherited metabolic diseases characterized by diffuse hypopigmentation in skin, hair and eyes; caused by partial or complete absence of melanin in the melanocytes The number of epidermal and follicular melanocytes is normal.

7 (8) types are differentiated on the basis of molecular differences:

• OCA 1 (tyrosinase-negative OCA): Based on reduced or absent tyrosinase activity; about 80 mutations in the tyrosinase gene(TYR) have been described so far. OCA1A is the classic tyrosinase-negative oculocutaneous albinism; OCA 1B is also known as yellow albinism. OCA1Ts refers to temperature-sensitive oculocutaneous albinism (hair on cooler parts of the body darkens in the course of life)
• OCA 2 (tyrosinase-positive OCA): Caused by mutations in the(OCA2 gene/P gene); the protein encoded by this gene increases melanin synthesis via a chloride channel by modulating melanosome pH (Bellono NW et al. 2014).The regulation of pH in melanosomes is of crucial importance. OCA 2 is also referred to as brown albinism or brown African albinism.
• OCA 3 (OMIM 203290)- Red albinism: Caused by mutations in the tyrosinase-related protein gene(TYRP1 gene; the Tyrp1 protein is a melanocyte-specific gene product involved in eumelanin synthesis). OCA3 is only associated with mild ocular symptoms. Often remains clinically undetected. Frequently described in African-American ethnic groups.
• OCA 4 (OMIM 606574): Caused by mutations of a "membrane associated transporter protein" gene(SLC45A2 gene), which encodes a transport protein for melanin precursors. Variable clinical symptoms comparable to OCA type 2. Common in Korea and Japan.
• OCA 5: OCA 5 has been described in a Pakistani family (white skin, golden hair and eye symptoms). The gene is still unknown; it could be assigned to chromosome locus 4q24, a gene locus that probably codes for lysosomal proteins (Kausar T et al. 2013).
• OCA 6: OCA 6, like OCA 4, is a mutation of the transporter protein encoded by SLC24A5 on chromosome 15q21.1. The encoded protein is a calcium-potassium-sodium antiporter that transports 1 Ca(2+) and 1 K(+) to the melanosome in exchange for 4 cytoplasmic Na(+).
• In OCA7 (OMIM: 614537) a mutation in the"LRMDA gene" localized on chromosome 10q 22.2-22.3 was detected. This gene codes for a protein that is important for melanocyte differentiation. This rather mild variant was described in a consanguineous Faroese family (Gronskov K et al. 2013).

• OCA8 was identified due to a DCT gene mutation. DCT stands for: dopachrome tautomerase. The gene is located on chromosome 13q32.1 and encodes the L-dopachrome tautomerase TYRP2, which plays a role in melanin biosynthesis.

Further OCA genotypes are expected in the future.

The most common inherited disease with diffuse depigmentation of the skin. The prevalence is estimated at 1:17,000 - 1:20,000 inhabitants; in some African strains it is 1:1,500 inhabitants.

For the tyrosinase-negative subtype OCA1 (affects 40% of all forms of albinism), the estimated prevalence in the European population is 1:40,000.

The tyrosinase-positive subtype OCA2 (affects 50% of all forms of albinism worldwide) occurs predominantly in the African population. In South Africa and Tanzania, the prevalence is 1:1,400 to 1:10,000 inhabitants (cited in Kubasch A 2017)

All types of oculocutaneous albinism (OCA) have an autosomal recessive mode of inheritance, except for a few families with autosomal dominant OCA. The disease is caused by mutations that directly affect the tyrosine gene TYR, or genes of proteins that regulate the processing of the copper-containing enzyme tyrosinase and the biosynthesis of melanin in the melanosomes and the ejection of mature melanosomes into the epidermis (cited in Kubasch A et al. 2017).

Despite various preclinical approaches (e.g. tyrosinase gene transfer, etc.), the only therapeutic options remaining are strict physical and chemical sun protection. Regular dermatological check-ups are necessary (incidences of basal cell carcinoma and squamous cell carcinoma are significantly increased, but not of malignant melanoma).

Oculocutaneous albinism can be associated with some rare syndromes:

• Waardenburg Syndrome
• Hermansky-Pudlak syndrome
• Chediak Higashi Syndrome
• Griscelli Syndrome

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