What is the primary cause of oculocutaneous albinism (OCA), a condition characterized by the lack of melanin production?

Oculocutaneous Albinism: Primary Cause and Pathophysiology

Oculocutaneous albinism (OCA) is primarily caused by a lack of melanization of melanocytes, not by the absence of melanocytes or always due to tyrosinase deficiency. The condition results from genetic mutations affecting melanin biosynthesis or distribution within melanocytes that are present but dysfunctional.

Types and Genetic Basis

OCA is a heterogeneous group of autosomal recessive disorders characterized by hypopigmentation of the eyes, skin, and hair. There are several types:

1. OCA1 (Tyrosinase-related)

   • OCA1A: Complete absence of tyrosinase activity, resulting in no melanin production throughout life 1
   • OCA1B: Reduced tyrosinase activity, allowing some pigment accumulation over time 1

2. OCA2 (P gene-related): Most common form worldwide, caused by mutations in the OCA2 gene 2

3. OCA3 (TYRP1-related): Caused by mutations in the tyrosinase-related protein 1 gene 3

4. OCA4 (SLC45A2-related): Caused by mutations in the SLC45A2 gene 3

5. Newer types: OCA5, OCA6 (SLC24A5), and OCA7 (C10orf11) have been more recently identified 3

Pathophysiology

The key pathophysiological feature in all forms of OCA is the lack of melanization of melanocytes rather than the absence of melanocytes themselves 3. This is important to understand because:

• Melanocytes are present in normal numbers and distribution in the skin, hair follicles, and eyes
• The defect lies in the melanin biosynthesis pathway or melanin transport mechanisms
• In OCA1, tyrosinase (the key enzyme in melanin synthesis) is either absent or dysfunctional
• In other forms of OCA, different proteins involved in melanin production or distribution are affected

Clinical Manifestations

The clinical presentation varies depending on the type of OCA but typically includes:

• Hypopigmentation of skin, hair, and eyes
• Ocular abnormalities (nystagmus, photophobia, reduced visual acuity)
• Increased susceptibility to UV radiation damage and skin cancer 4

Diagnostic Approach

Diagnosis is based on:

1. Clinical features (hypopigmentation)
2. Ophthalmologic examination
3. Genetic testing to identify specific mutations 1

Management Considerations

Management focuses on:

1. Protection from UV radiation to prevent skin damage and cancer
2. Regular skin monitoring for early detection of malignancies 4
3. Visual rehabilitation and correction
4. Genetic counseling for affected families

Answer to Multiple Choice Question

Based on the evidence provided, the correct answer is: C. Due to lack of melanisation of melanocytes

This is the fundamental defect in OCA - melanocytes are present but cannot produce or distribute melanin properly due to various genetic mutations affecting the melanin biosynthesis pathway.

Option A (Always due to tyrosinase deficiency) is incorrect because while tyrosinase deficiency causes OCA1, other forms of OCA are caused by mutations in different genes.

Option B (Due to absence of melanocytes) is incorrect because in OCA, melanocytes are present but cannot produce or distribute melanin properly.