What causes Oculocutaneous albinism and how is it managed?

Oculocutaneous Albinism: Causes and Management

Oculocutaneous albinism (OCA) is primarily caused by lack of melanization of melanocytes rather than tyrosinase deficiency or absence of melanocytes. The condition results from genetic mutations affecting melanin biosynthesis while melanocytes are present but unable to produce normal amounts of pigment.

Causes of Oculocutaneous Albinism

Genetic Basis and Types

OCA is a group of inherited disorders characterized by reduced melanin biosynthesis. There are several types with different genetic causes:

1. OCA1 (Tyrosinase-related OCA) 1, 2

   • Caused by mutations in the TYR gene (encoding tyrosinase)
   • Accounts for approximately 85% of cases with white hair at birth 2
   • Subtypes:
     • OCA1A: Complete absence of tyrosinase activity with no melanin production throughout life
     • OCA1B: Partial tyrosinase activity with some pigment accumulation over time

2. OCA2 (P gene-related OCA) 1, 3

   • Caused by mutations in the OCA2 (P) gene
   • Second most common form (12.2% of cases in some populations) 4
   • The P protein modulates the processing and transport of tyrosinase 3

3. OCA3 (TYRP1-related OCA) 1, 4

   • Caused by mutations in the TYRP1 gene
   • Less common (approximately 1.2% of cases) 4

4. OCA4 (SLC45A2/MATP-related OCA) 1, 4

   • Caused by mutations in the SLC45A2 gene
   • Rare (less than 1% of cases in some populations) 4

Pathophysiology

The key pathophysiological mechanism in OCA is not the absence of melanocytes but rather their inability to produce melanin normally 1, 3. In OCA:

• Melanocytes are present in normal numbers
• The melanosomes (pigment-producing organelles) are present but lack normal melanin content
• In OCA2, the P protein affects the processing and transport of tyrosinase, leading to altered melanin synthesis 3

Clinical Manifestations

Ocular Manifestations

• Congenital nystagmus
• Iris hypopigmentation and translucency
• Reduced pigmentation of retinal pigment epithelium
• Foveal hypoplasia
• Reduced visual acuity (typically 20/60 to 20/400)
• Refractive errors
• Color vision impairment
• Photophobia
• Misrouting of optic nerves leading to strabismus and reduced stereoscopic vision 1

Cutaneous Manifestations

• Hypopigmentation of skin and hair (varying degrees based on OCA type)
• Increased susceptibility to sunburn
• Elevated risk of skin cancer 1, 5

Management of Oculocutaneous Albinism

Ocular Management

• Vision correction: Prescription glasses (possibly bifocals) for reduced visual acuity 1
• Photophobia management: Dark glasses or photochromic lenses 1
• Strabismus and nystagmus: Surgical correction as necessary 1

Skin Protection and Monitoring

• Sun protection: Rigorous use of sunscreens, protective clothing, and sun avoidance 6
• Skin cancer surveillance: Regular skin examinations for early detection of skin cancers 6, 1
• Patient education: Extensive and repetitive education regarding sun avoidance and protection 6

Genetic Counseling

• Carrier detection and prenatal diagnosis are possible when disease-causing mutations have been identified in the family 1
• All forms of OCA are inherited as autosomal recessive disorders 1

Psychosocial Support

• Address psychosocial challenges that may affect quality of life 5
• Educational interventions to improve understanding of the condition 5

Prognosis

People with OCA generally have:

• Normal lifespan
• Normal development and intelligence
• Normal fertility 1

The main ongoing concerns are visual impairment and increased risk of skin cancer, which require lifelong management and monitoring.