Alex V. Levin

BASICS

DESCRIPTION

• Oculocutaneous albinism (OCA) is a group of hereditary diseases marked by absent or decreased melanin biosynthesis within melanocytes, or abnormalities of melanosome formation or function.

– Hypopigmentation of the hair, skin, and eyes

– Four types of OCA

– OCA1: Usually white hair, pale skin, and light irides

– OCA2: Usually less severe than type 1, more frequent in African Americans, Africans and some Native Americans

– OCA3: Brown (BOCA) or rufous (ROCA), more frequent in Africa

– OCA4: Similar to type 2, more frequent in Japan and Turkey

– Because of phenotypic overlap, the types of OCA are most accurately distinguished by their genetic defects

• Ocular albinism (OA) is a disorder marked by abnormal melanosomes (macromelanosomes), though each is fully pigmented.

– Signs and symptoms are mostly limited to the eye.

EPIDEMIOLOGY

Incidence

• Varies by region, about 1 in 20,000 births worldwide

• The highest incidence in the world is found in the Kuna Indians of the San Blas Islands of Panama

• OCA1 and OA1 are the most common forms

Prevalence

• 1 in 17,000 people have one of the forms of albinism

• 1 in 70 people are carriers for one of the implicated genes

• 1 in 60,000 males is affected by ocular albinism type 1, also known as the Nettleship-Falls type, the most common type of ocular albinism

RISK FACTORS

Genetics

• Oculocutaneous albinism is usually autosomal recessive. Autosomal dominant is rare.

• Patients typically harbor 2 different mutations in 1 gene for oculocutaneous albinism (i.e., compound heterozygotes).

– Tyrosinase (TYR) – OCA1

– P-gene – OCA2

– Tyrosinase-related protein 1 (TRP1) – OCA3

– Membrane-associated transporter protein (MATP, also called SLC45A2) – OCA4

• Ocular albinism is usually X-linked recessive, female carriers may manifest signs by lyonization

– G protein-coupled receptor 143 (GPR143, albinism type 1). The gene protein controls the growth and maturation of melanosomes.

– Autosomal recessive ocular albinism has also been described.

– Digenic inheritance has also been reported.

GENERAL PREVENTION

• Genetic counseling

• Prenatal molecular diagnosis available when cultural attitudes may result in psychosocial disability

PATHOPHYSIOLOGY

Hypopigmentation in RPE during early gestation leads to macular hypoplasia, which in turn leads to delayed ganglion cell differentiation and abnormal chiasmal decussation.

ETIOLOGY

The different types of oculocutaneous albinism are due to genes involved in the biosynthesis of melanin and melanosomes in melanocytes (see “Genetics”).

COMMONLY ASSOCIATED CONDITIONS

• Hermansky-Pudlak syndrome

– Platelet aggregation deficiency. More prevalent in Puerto Ricans and Swiss. May have accumulation of ceroid throughout the body, leading to pulmonary fibrosis, granulomatous enteropathic disease, and renal failure

• Chediak–Higashi syndrome

– Impaired bactericidal activity and thus an increased susceptibility to infection

• Griscelli syndrome

– Large clumps of pigment in hair shafts. Immunodeficiency in one variant; neurologic deficits in another

• Prader-Willi

– Neonatal hypotonia, hyperphagia, and obesity, small hands and feet, hypogonadism, mental retardation

• Angelman syndrome

– Neonatal hypotonia, developmental delay, microcephaly, severe mental retardation, ataxic movements, inappropriate laughter

DIAGNOSIS

• Ophthalmic features of oculocutaneous and ocular albinism include various degrees of:

– Congenital nystagmus

– Strabismus

– Iris transillumination

– Photophobia

– Hypopigmentation of the fundus

– Macular hypoplasia

– Reduced visual acuity (20/40–20/400)

– Refractive errors

– Amblyopia due to strabismus or anisometropia

– Grey optic nerves with or without optic nerve hypoplasia

• Cutaneous features of oculocutaneous albinism include various degrees of:

– Skin hypopigmentation

– Hair hypopigmentation

– May have nevi (ephelides)

HISTORY

• Family history

• Decreased vision

• Photosensitivity

• Review of systems should assess easy bruising and bleeding (Hermansky–Pudlak) and propensity for infection (Chediak–Higashi)

PHYSICAL EXAM

• External examination including hair and skin

• Complete ophthalmic examination including refraction, motility, slit lamp examination (iris transillumination defects), and dilated fundus examination (hypoplastic fovea, hypopigmented retina with highly visible choroidal vasculature)

DIAGNOSTIC TESTS & INTERPRETATION

Diagnostic Procedures/Other

• Prenatal diagnosis possible if gene mutation known

• Albinism is a clinical diagnosis which can be confirmed in some cases with DNA testing

• Optical coherence testing (OCT) demonstrates macular hypoplasia

• Multichannel visual evoked potentials demonstrate excessive decussation of retinal ganglion cell axons at the chiasm in most cases

• Molecular genetic testing may determine the specific mutations and thus helps identify the subtype of oculocutaneous albinism

• Tests for OCA1, OCA2, and OA1 are available clinically

• Tests for other genes only for research purposes

Pathological Findings

• Macromelanosomes may be seen on skin biopsy in OA1, Hermansky–Pudlak syndrome, and Chediak–Higashi syndrome.

TREATMENT

ADDITIONAL TREATMENT

General Measures

• Address refractive error with glasses or contact lens

• Tinted or polychromic lens for photophobia

• Treat amblyopia, which can result from strabismus or anisometropia

• High contrast reading material and large type fonts

• Distance low vision aids (usually after first grade)

• Suntan lotion (minimum 15 SPF) and other protective measures against UV sunlight exposure

SURGERY/OTHER PROCEDURES

Eye muscle surgery for strabismus or nystagmus

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

• Ophthalmologist

• Low vision

• Primary care doctor or dermatologist for periodic skin examinations

• Hematology evaluation if Hermansky–Pudlak or Chediak–Higashi syndrome a concern

PATIENT EDUCATION

The National Organization for Albinism and Hypopigmentation (http://www.albinism.org)

PROGNOSIS

• Normal lifespan, development, intelligence, fertility

• Increased risk of skin cancer

COMPLICATIONS

• Visual loss

• Actinic keratosis, squamous cell carcinoma, and basal cell carcinoma in sun-exposed areas

ADDITIONAL READING

• Grønskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet Journal of Rare Diseases 2007;2:43.

• Okulicz JF, Shah RS, Schwartz RA, et al. Oculocutaneous albinism. J Eur Acad Dermatol Venereol. 2003;17(3):251–256.

CODES

ICD9

270.2 Other disturbances of aromatic amino-acid metabolism

CLINICAL PEARLS

• Oculocutaneous albinism (OCA) is a group of hereditary diseases marked by absent or decreased melanin or melanosome synthesis within melanocytes.

• OCA is usually autosomal recessive and affects the eyes, skin, and hair.

• Ocular albinism is an X-linked recessive disorder generally limited to the eye, due to a genetic defect leading to macromelanosomes.

• Visual acuity is usually reduced.

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