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X-linked recessive ocular albinism
X-linked recessive ocular albinism (XLOA) is a rare disorder characterized by ocular hypopigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity in males.
ORPHA:54Classification level: Disorder
The estimated birth prevalence is from 1/60,000 to 1/150,000 live male births.
Nystagmus, sometimes associated with head nodding, usually develops in affected males within the first 3 months of life. It can diminish with time but rarely completely disappears. Best-corrected visual acuity is usually between 20/40 and 20/200, and often improves during childhood. Most patients have photodysphoria, strabismus and absent or reduced stereoacuity. Ocular findings include iris translucency, foveal hypoplasia, hypopigmentation of the fundus and excessive crossing of the nerves from the eye to the brain. Some males have irregular hypopigmented spots on the extremities, but they escape clinical notice. Carrier women, in the vast majority of cases, are asymptomatic. XLOA is less severe in those with dark constitutive skin pigmentation than those who are more lightly pigmented.
XLOA is caused by a mutation in the G-protein coupled receptor 143 GPR143 gene located at Xp22.3 that encodes for a membrane glycoprotein found in melanosomes. The few cases where females displayed the same phenotypes as males are thought to have been due to either a homozygous mutation in GPR143, partial monosomy of the X chromosome or X-chromosome inactivation.
Diagnosis is based on the presence of characteristic ocular findings and molecular genetic testing. A family history consistent with X-linked inheritance provides further evidence of XLOA. A GPR143 mutation is found in 90% of affected males. Melanin macroglobules (macromelanosomes) are usually found on skin biopsy but are not pathognomonic. Female obligate carriers are identified by finding patchy mottling or streaking of pigment in the midperipheral retina (pigmentary mosaicism), representing random X inactivation.
Differential diagnoses include various types of oculocutaneous albinism (OCA), blue cone monochromatism, congenital stationary night blindness, ocular albinism with sensorineural deafness, cone dystrophy with supernormal rod response, Leber congenital amaurosis, complete and incomplete achromatopsia, X-linked congenital nystagmus (see these terms), and autosomal dominant infantile nystagmus syndrome.
Prenatal testing can be performed when women are known carriers of the GPR143 mutation, using chorionic villus sampling or amniocentesis. Preimplantation genetic diagnosis may be available.
XLOA is inherited in an X-linked recessive manner so genetic counseling is possible. Affected males do not transmit the disease causing mutation to their sons but all of their daughters become carriers. Female carriers have a 50% risk of transmitting the mutation to their offspring, whether male or female; however, only sons with the mutation will display the disease. Carrier testing can be offered to at-risk individuals.
Management and treatment
Annual ophthalmologic examinations are recommended for patients under the age of 16, and after that every 2-3 years. Treatment consists of visual correction with eyeglasses or contact lenses. Sunglasses, photochromic lenses or special filter glasses can help to relieve photodysphoria. Extraocular muscle surgery can be performed to restore alignment and/or improve a head posture that is compensatory for nystagmus. Visual aids, changing electronic font size, and special education for the visually impaired may be needed. Patients should wear hats/caps, clothing, and sunscreen on sun-exposed skin to prevent burning and skin cancer.
XLOA is not life threatening. The reduced visual acuity and the social consequences of albinism can however have an impact on a patient's daily life.