Oculocutaneous albinism type 1A: A case report
Published Web Locationhttps://doi.org/10.5070/D31w92n374
Oculocutaneous albinism type 1A: A case reportDepartment of Medical Genetics, Erzurum Training and Research Hospital, Turkey
Ali Karaman MD
Dermatology Online Journal 14 (11): 13
The term, oculocutaneous albinism (OCA), describes a group of inherited disorders of melanin biosynthesis that exhibits congenital hypopigmentation of ocular and cutaneous tissues. The clinical spectrum of OCA ranges from a complete lack of melanin pigmentation to mildly hypopigmented forms. OCA1A is the most severe type with a complete lack of melanin production throughout life; the milder forms OCA1B, OCA2, OCA3 and OCA4 show some pigment accumulation over time. Clinical manifestations include various degrees of congenital nystagmus, iris hypopigmentation and translucency, reduced pigmentation of the retinal pigment epithelium, foveal hypoplasia, reduced visual acuity and refractive errors, color vision impairment, and prominent photophobia. All four types of OCA are inherited as autosomal recessive disorders. At least four genes are responsible for the different types of the disease (TYR, OCA2, TYRP1, and MATP). Diagnosis is based on clinical findings of hypopigmentation of the skin and hair in addition to the characteristic ocular symptoms. Herein we present a case with OCA1A.
A 13-year-old boy, the first child of an unrelated couple, was born following normal gestation and delivery. At term, birth weight was 3450 g, and length was 53 cm. OCA was noted at birth; there was total depigmentation of the skin, hair, and iris. The family history was unremarkable.
The patient had white hair, eyebrows, eyelashes, and depigmented skin (Fig. 1). Ophthtalmologic examination revealed chracteristic iris depigmentation and translucency, retinal depigmentation, foveal hypoplasia, misrouting of the optic nerve fibers, reduced visual acuity (1/10), prominent photophobia, and nystagmus. He had normal mental development. The boy was examined carefully to exclude other congenital deformities. He did not have any abnormalities of internal organs.
Diagnosis. Oculocutaneous albinism type 1A.
Oculocutaneous albinism is a group of congenital heterogeneous disorders of melanin biosynthesis within the melanocytes. Albinism can affect people of all ethnic backgrounds and has been extensively studied. Approximately one in 17,000 people have one of the types of albinism . This suggests that about 1 in 70 people carry a gene for OCA. Oculocutaneous albinism 1 has a prevalence of approximately 1 per 40,000  in most populations but is very uncommon among African-Americans. In contrast, OCA2 is the most common type of albinism in African Black OCA patients. The overall prevalence of OCA2 is estimated to be 1:36,000 in the USA, but is about 1:10,000 among African-Americans . Oculocutaneous albinism 3 has been reported to affect 1:8,500 individuals in Africa, whereas it is very rare in Caucasians and Asian populations . Recently, mutations in a fourth gene were shown to be the cause of another form of albinism, OCA4 , OCA4 has been estimated to affect approximately 18 percent of Japanese patients with albinism .
All types of OCA have similar ocular findings, including various degrees of congenital nystagmus, hypopigmentation of the iris leading to iris translucency, reduced pigmentation of the retinal pigment epithelium, foveal hypoplasia, reduced visual acuity usually in the range 20/60 to 20/400 and refractive errors, and sometimes a degree of color vision impairment [1, 7]. Photophobia may be prominent. A characteristic finding is misrouting of the optic nerves, consisting in an excessive crossing of the fibers in the optic chiasma that can result in strabismus and reduced stereoscopic vision . The abnormal crossing of fibers can be demonstrated by monocular visual evoked potential . Absence of misrouting excludes the diagnosis of albinism.
In OCA1A the hair, eyelashes, and eyebrows are white and the skin is white and does not tan. Irises are light blue and fully translucent. Pigment does not develop and amelanotic nevi may be present. The symptoms do not vary with age or race. Visual acuity is 1/10 or less and photophobia is intense. In OCA1B, the hair and skin may develop some pigment with time (after 1 to 3 years) and blue irises may change to green/brown. Visual acuity is 20/100.
In OCA2, the amount of cutaneous pigment may vary and newborns nearly always have pigmented hair. Nevi and ephelids are common. Iris color varies. Visual acuity is usually better than in OCA1. In Africans, brown OCA is associated with light brown hair and skin, and gray irises. OCA3 results in red OCA in African individuals, who have red hair and reddish brown skin. Visual anomalies are not always detectable. Oculocutaneous albinism 4 cannot be distinguished from OCA2 on clinical findings.
At least four genes are responsible for the different types of OCA (OCA1-4). Oculocutaneous albinism 1 is caused by mutations in the tyrosinase gene (TYR) on chromosome 11q14.3 . The gene consists of 5 exons spanning about 65 kb of genomic DNA and encoding a protein of 529 amino acids . TYR is a copper-containing enzyme that catalyzes the first two steps in the melanin biosynthesis pathway, converting tyrosine to L-dihydroxy-phenylalanine (DOPA) and subsequently to DOPAquinone .
Mutations completely abolishing tyrosinase activity result in OCA1A, whereas mutations rendering some enzyme activity result in OCA1B, allowing some accumulation of melanin pigment over time. Mutations in the OCA2 gene cause the OCA2 phenotype . The gene consists of 24 exons spanning almost 345 kb of genomic DNA in the region 15q11.2-q12 and encodes a protein of 838 amino acids . OCA2 protein is important for normal biogenesis of melanosomes and for normal processing and transport of melanosomal proteins such as TYR and TYRP1 .
Oculocutaneous albinism 3 is caused by mutations in tyrosinase-related protein 1 gene (TYRP1) on chromosome 9p23 . TYRP1 spans almost 17 kb genomic DNA and consists of 8 exons encoding a protein of 536 amino acids . Tyrosinase-related protein 1 is an enzyme in the melanin biosynthesis pathway that catalyzes the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) monomers into melanin. Studies of mouse melanocytes showed that Tyrp1 functions to stabilize Tyr and that mutations in Tyrp1 cause a delayed maturation and an early degradation of Tyr .
Mutations in the membrane-associated transporter protein gene (MATP) cause OCA4 . The MATP gene consists of 7 exons spanning approximately 40 kb of genomic DNA and mapping to chromosomal position 5p13.3. The MATP protein of 530 amino acids contains 12 putative transmembrane domains and shows sequence and structural similarity to plant sucrose transporters . Mutations in MATP were found for the first time in a Turkish OCA patient .
The diagnosis of OCA is based on clinical findings of hypopigmentation of the skin and hair, in addition to the characteristic ocular symptoms. However, due to the clinical overlap between the OCA subtypes, molecular diagnosis is necessary in order to establish the gene defect and thus the OCA subtype. Molecular genetic testing is based on mutational analysis of the genes, by standard screening methods such as denaturing high performance liquid chromatography (DHPLC) or single stranded conformational polymorphism (SSCP), followed by DNA sequencing.
All four types of OCA are inherited as autosomal recessive disorders. Thus, the parents of an affected child are obligate carriers and the recurrence risk for another affected child is 25 percent. Offspring of an affected person are obligate carriers. Heterozygous carriers are asymptomatic. Carrier detection and prenatal diagnosis are possible when the disease causing mutations have been identified in the family. Prenatal testing can be done on DNA extracted from chorionic villus sampling at 10-12 weeks gestation or on DNA extracted from cultured amniocytes. Pre-implantation diagnosis using molecular genetic analysis is also possible in principle.
Reduced visual acuity can be helped in various ways. Glasses, possibly bifocals, may often be of sufficient help. Photophobia can be improved with dark glasses or photochromic lenses that darken with exposure to bright light. Nystagmus may be improved by using contact lenses or undergoing surgery on the eye muscles. Children should be given special attention at school, for instance with high contrast written material, large type textbooks, various optic devices such as enlargement machines, and special computers. Most people with severe forms of OCA do not tan and easily get sunburned. In these cases sunscreen and protective clothing are recommended. The incidence of skin cancer is increased in patients with OCA . Regular skin checks for early detection of skin cancer should be offered.
The differential diagnosis includes ocular albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome, Waardenburg syndrome type II, Prader Willi syndrome, and Angelman syndrome. Persons with OCA have a normal lifespan, normal development, normal intelligence, and normal fertility.
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