Dermatology MCQ - Genetic Disorders - Oculocutaneous albinism (OCA)

A 6-month-old infant with very fair skin, white hair, and nystagmus is brought to clinic. The parents are concerned about the infant's poor vision and sensitivity to light. Genetic testing reveals a mutation in the tyrosinase gene (TYR) resulting in complete absence of enzyme activity. What is the most accurate classification, visual prognosis, and critical management priority for this child?

A. Oculocutaneous Albinism Type 1A (Tyrosinase-negative OCA); poor visual acuity but stable; management priority is rigorous sun protection to prevent skin cancer.
B. Oculocutaneous Albinism Type 1B (Yellow OCA); moderate visual impairment; management priority is low-vision aids.
C. Oculocutaneous Albinism Type 2 (Tyrosinase-positive OCA); variable pigmentation and vision; management priority is genetic counseling.
D. Hermansky-Pudlak Syndrome Type 1; includes bleeding diathesis and lung disease; management priority is hematologic surveillance.
E. Chediak-Higashi Syndrome; includes immune deficiency and neurological issues; management priority is infection prevention.

Correct Answer: A. Oculocutaneous Albinism Type 1A (Tyrosinase-negative OCA); poor visual acuity but stable; management priority is rigorous sun protection to prevent skin cancer.

Answer and Explanation

The correct answer is A. This question describes classic Oculocutaneous Albinism Type 1A (OCA1A), the most severe form. The key clues are the complete absence of melanin (white hair, very fair skin) from birth, nystagmus, photophobia, and poor vision due to foveal hypoplasia and misrouting of the optic nerves. A mutation in the TYR gene causing complete absence of tyrosinase enzyme activity is diagnostic for OCA1A. The visual acuity is significantly reduced and stable (non-progressive). While low-vision aids are important, the most critical medical priority from infancy is rigorous, lifelong sun protection to prevent the severe actinic damage and dramatically increased risk of cutaneous squamous cell carcinoma and basal cell carcinoma.

Why the Other Options are Incorrect:

• B. Oculocutaneous Albinism Type 1B (Yellow OCA): This is also caused by TYR mutations, but with residual enzyme activity. Affected individuals are born with white hair/skin but develop some yellow/red hair pigment over time. The description of persistent white hair points to the complete absence seen in OCA1A.

• C. Oculocutaneous Albinism Type 2 (Tyrosinase-positive OCA): Caused by mutations in the OCA2 gene. Individuals have some pigment at birth (light yellow/blond hair, some skin color) that may increase with age. The visual prognosis is similarly poor, but the description of complete absence of pigment fits OCA1A.

• D. Hermansky-Pudlak Syndrome (HPS): This is a syndromic form of albinism. While it includes oculocutaneous albinism, it is distinguished by platelet storage pool deficiency (causing easy bruising/bleeding) and, in some types, pulmonary fibrosis and granulomatous colitis. The question does not mention bleeding or other systemic issues.

• E. Chediak-Higashi Syndrome (CHS): This is another syndromic albinism characterized by silvery hair, severe immune deficiency, neurological deterioration, and giant granules in leukocytes. It does not present with complete absence of pigment (hair has a metallic sheen) and includes severe infections, not described here.

Additional High-Yield Information for Exams:

• Pathogenesis & Genetics: OCA is a group of autosomal recessive disorders affecting melanin synthesis in the skin, hair, and eyes. The lack of melanin in the retinal pigment epithelium and fovea causes the universal ocular findings: foveal hypoplasia, nystagmus, strabismus, reduced visual acuity (usually 20/100 to 20/400), photophobia, and iris translucency.

• Classification:

  • OCA1: TYR gene mutation. 1A: No tyrosinase activity, no melanin. 1B: Reduced activity, some melanin later.

  • OCA2: OCA2 gene mutation (most common worldwide). Some pigment present.

  • OCA3: TYRP1 mutation (rufous albinism), seen mainly in African populations.

  • OCA4: SLC45A2 mutation, similar to OCA2.

• Differential Diagnosis: The main differential is between non-syndromic OCA (types 1-4) and syndromic albinism:

  • Hermansky-Pudlak Syndrome (HPS): Bleeding diathesis is the key clue.

  • Chediak-Higashi Syndrome (CHS): Recurrent pyogenic infections and neurological issues.

• Associated Conditions & Prognosis:

  • Visual Prognosis: Poor but stable. Vision does not deteriorate further from the albinism itself, but refractive errors and strabismus need correction.

  • Skin Cancer Risk: Extremely high, especially in sunny climates. Squamous cell carcinoma is a major cause of morbidity and mortality in adulthood. Actinic damage occurs very early.

• Management & Rationale:

  • Rationale: A multidisciplinary approach focusing on maximizing visual function and preventing skin cancer.

  • First-line/Obligatory Measures:

    1. Dermatologic: Absolute, rigorous sun protection from infancy. This includes high-SPF broad-spectrum sunscreen, protective clothing, hats, and UV-blocking sunglasses. Regular skin exams to detect pre-cancers and cancers early.

    2. Ophthalmologic: Early referral to pediatric ophthalmology. Management includes correction of refractive errors, treatment of strabismus, and provision of low-vision aids (magnifiers, large-print materials). Tinted lenses help with photophobia.

  • Other: Genetic counseling for the family. For suspected syndromic forms, specific workups are needed (e.g., platelet aggregation studies for HPS).