Albinism pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shadan Mehraban, M.D.[2]

Overview

Melanocytes are derived from neural crest ectoderm and are found in hair follicles, skin, eyes, and inner ear. Melanocytes produce melanin which protects skin from ultraviolet. Tyrosinase converts tyrosine to DOPA, dopaquinone, and then melanin. Mutation in Tyrosinase enzyme is responsible for causing albinism. Additionally, melanin is responsible for development of the fovea, optic nerves, optic tracts, and visual cortex.Decussation of some optic nerve fibers at optic chiasm are essential for binocular vision. However, in albinism, most of nerve fibers decussate at optic chiasm and cause monocluar vision presented as strabismus. In ocular albinism, macular pigment is absent and fovea hypoplasia leads to decreased visual acuity.

Pathophysiology

Physiology

• Melanocytes are derived from neural crest ectoderm and are found in hair follicles, skin, eyes, and inner ear
• Melanocytes account for 5% to 10% of cells in epidermal basal layers
• Melanocytes contain melanosomes which produce melanin
• Melanin protects skin from ultraviolet; with sun exposure melanin pigment increases in the skin
• Apart from the photo-protective effect of melanin, it has some roles in the development of ocular structures as well as oculoneural pathways
• Melanin converts 2 forms named eumelanin and pheomelanin
• Eumelanin is responsible for black or brown skin color and protects skin from ultraviolet B
• Pheomelanin is responsible for red or blond hair and light-colored, and ruddy skin
• On melanocytes, activation of melanocortin one receptors (MC1R) lead to synthesis of eumelanin over pheomelanin

Pathogenesis

• Mutation in Tyrosinase enzyme is responsible for causing albinism
• Tyrosinase converts tyrosine to DOPA and then dopaquinone; subsequenstly, dopaquionone converts to either eumelanin or pheomelanin
• Tyrosinase mutation is seen in oculocutaneous albinism 1 (OCA1) and autosomal-recessive ocular albinism (AROA)
• Lack of melanin increase chances of sun-damage related diseases including actinic keratosis and UV-related malignancies
• Ocular albinism pathway:
  • In uterus, melanin is responsible for development of the fovea, optic nerves, optic tracts, and visual cortex
  • Decussation of some optic nerve fibers at optic chiasm are essential for binocular vision
  • In people without albinism, about 45% of optic nerve fibers from the temporal part of retina do not cross the optic chiasem to controlateral lateral geniculate nucleus
  • In albinism, most of nerve fibers decussate at optic chiasm and cause monocluar vision
  • Monocular vision is manifested as strabismus
  • In albinism, macular pigment is absent and fovea hypoplasia leads to decreased visual acuity
  • Visual acuity ranges from 20/60 to 20/400

Genetics

• Genetic mutation in albinism include:
  • Tyrosinase in OCA1; autosomal recessive
  • P protein in OCA2;autosomal recessive
  • Tyrosinase-related protein 1 (TYRP1)in OCA3; autosomal recessive
  • solute carrier family 45, member 2 (SLC45A2) in OCA4; autosomal recessive
  • Gene mutation in OCA5 is not identified; autosomal recessive
  • SLC24A5 in OCA6; autosomal recessive
  • Leucine-rich melanocyte differentiation associated protein (LRMDA) in OCA7; autosomal recessive
  • Gene mutation in Hermansky-Pudlak syndrome (HPS) subtypes are as following:
    • HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1; autosomal recessive
  • LYST in [[Chediak-Higashi syndrome ](]; autosomal recessive
  • GPR143 in ocular albinism 1 (OA1) ;X-linked

Histological Findings

• Macromelanosomes are seen in male patients with albinism and female carriers of OA1