Oculocutaneous albinism type 1A (ORPHA:79431)
A severe form of oculocutaneous albinism type 1 (OCA1) characterized by complete absence of melanin and manifesting as white hair and skin, blue, fully translucent irises, nystagmus and misrouting of the optic nerves.
Epidemiology
The worldwide prevalence of OCA1 is estimated at 1/40,000. OCA type 1A (OCA1A) is considered to account for about half of the overall OCA1 cases among non-Hispanic, Caucasian patients.
Clinical description
Patients have white skin and hair at birth. Irises are blue to pink and fully translucent. These features do not change throughout a patient's life. Nystagmus may be present at birth or it may develop in the first 3 to 4 months of life. It continues throughout life but usually slows down after childhood and is less noticeable when a person is relaxed and well rested. Visual acuity ranges from 20/100 and 20/400 and an alternating strabismus is often present. The reduction in visual acuity is associated with foveal hypoplasia. Severe photophobia is common. Nevi and ephelides are common but are unpigmented and pink. Patients do not tan, and if proper sun protection methods are not followed, skin becomes rough, coarse, thickened and can have solar keratoses. Patients have an increased risk of developing basal and squamous cell carcinomas but melanomas are rare.
Etiology
OCA1A is caused by a mutation in the TYR gene (11q14.2) encoding tyrosinase. The mutation leads to a completely inactive or incomplete tyrosinase enzyme polypeptide. Melanocytes contain no melanin, as without this enzyme the melanin biosynthetic pathway is blocked.
Diagnostic methods
The characteristic clinical findings along with confirmatory genetic testing are used to diagnose OCA1A. Ophthalmologic examination reveals visualization of the choroidal blood vessels, reduced retinal pigment and foveal hypoplasia. Alternating strabismus, reduced stereoscopic vision, and an altered visual evoked potential (VEP) are associated with the characteristic misrouting of the optic nerves at the chiasm. Molecular genetic testing is usually necessary to make the correct diagnosis of this subtype.
Differential diagnosis
Differential diagnoses include the other forms of OCA and X-linked ocular albinism (XLOA) as well as syndromes with albinism as a feature such as Hermansky-Pudlak syndromes 1-11, Chediak-Higashi syndrome, Griscelli syndromes 1-3, and Waardenburg syndrome type II.
Antenatal diagnosis
Prenatal testing is possible for at risk pregnancies by molecular genetic testing.
Genetic counseling
This disorder is inherited autosomal recessively. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child at each pregnancy.
Management and treatment
Annual ophthalmologic examination is necessary and corrective lenses or glasses are given to improve visual acuity. Dark glasses may be needed to relieve photophobia. Strabismus surgery can be performed for functional or cosmetic reasons. Protection from sunlight is imperative and patients should wear clothing and sunscreen on exposed skin to prevent burning and reduce the risk of skin cancer. Annual skin examinations should also be performed to identify any pre-cancerous or cancerous lesions.
Prognosis
OCA1A is not life threatening, unless malignancies develop, and remains stable after childhood. The medical and social consequences can however have major impacts on a patient's daily life.

                            Last update: 
                            December 2020


                            - Expert reviewer(s): 
                            Dr Masahiro HAYASHI  - Dr Tamio SUZUKI