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

1. Baxter LL, Pavan WJ (2002) The oculocutaneous albinism type IV gene Matp is a new marker of pigment cell precursors during mouse embryonic development. Mech Dev 116: 209-212

2. Bellono NW et al. (2014) An intracellular anion channel critical for pigmentation. Elife: e04543).

3. Brilliant MH (2001) The mouse p (pink-eyed dilution) and human P genes, oculocutaneous albinism type 2 (OCA2), and melanosomal pH. Pigment Cell Res 14:86-93.

4. Gronskov K et al. (2013) Mutations in C10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism. Am J Hum Genet 92: 415-421.
5. Kamaraj B et al.(2014) Mutational analysis of oculocutaneous albinism: a compact review. Biomed Res Int doi: 10.1155/2014/905472.
6. Kausar T et al. (2013) OCA5, a novel locus for non-syndromic oculocutaneous albinism, maps to chromosome 4q24. Clin Genet 84:91-93.
7. King RA et al. (2003) Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype. Hum Genet 113: 502-513
8. Kubasch A et al. (2017) Oculocutaneous and ocular albinism. Dermatology 68: 867-875
9. King RA et al. (2003) MC1R mutations modify the classic phenotype of oculocutaneous albinism type 2 (OCA2). Am J Hum Genet 73: 638-645
10. Nakamura E et al. (2002) A novel mutation of the tyrosinase gene causing oculocutaneous albinism type 1 (OCA1). J Dermatol Sci 28: 102-105
11. Oetting WS et al. (2003) Oculocutaneous albinism type 1: the last 100 years. Pigment Cell Res 16: 307-311
12. Okulicz JF et al (2003) Oculocutaneous albinism. J Eur Acad Dermatol Venereol 17: 251-256

13. Power B et al. (2019) Hermansky-Pudlak syndrome and oculocutaneous albinism in Chinese children with pigmentation defects and easy bruising. Orphanet J Rare Dis 14:52

14. Rundshagen U et al. (2003) Mutations in the MATP gene in five German patients affected by oculocutaneous albinism type 4. Hum Mutat 23: 106-110
15. Terenziani M et al. (2003) Amelanotic melanoma in a child with oculocutaneous albinism. Med Pediatr Oncol 41: 179-180