Ocular Manifestations of Albinism
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Albinism refers to a group of hereditary disorders that involve an abnormality of melanin synthesis or distribution.
The term albinism comes from the Latin word albus, which means white, and, in 1908, Garrod first scientifically described it. [1] Clinically, albinism presents as a pigmentation abnormality of the skin, the hair, and/or the eyes. Albinism can be divided into 2 broad categories, as follows: oculocutaneous albinism and ocular albinism. Oculocutaneous albinism involves both the skin and the eyes, whereas ocular albinism mainly affects the eyes with minimal to no skin involvement.
The primary morbidity of both oculocutaneous albinism and ocular albinism is eye related. Signs and symptoms include photophobia, refractive errors, monocular vision, strabismus, pendular nystagmus, iris transillumination defects, foveal hypoplasia, and abnormal decussation of the optic nerve fibers. These ocular manifestations are almost always present in both forms of albinism; however, the degree of their presentation can vary depending on the type of albinism and the racial background of the patient.
The inheritance pattern of albinism is also quite variable. Oculocutaneous albinism is mostly an autosomal recessive disorder, whereas ocular albinism is transmitted as a sex-linked or autosomal recessive disease.
Oculocutaneous albinism is divided into approximately 10 different types. Two of the more common forms are type I (tyrosinase negative) [2] and type II (tyrosinase positive) oculocutaneous albinism. Patients with type I disease have no skin or ocular pigmentation, whereas those with type II disease can develop some pigmentation as they grow older.
Another important form of oculocutaneous albinism is type IB, which was previously called yellow mutant oculocutaneous albinism. Patients with type IB are similar to those with type I but can exhibit some pigmentation of their skin, hair, and ocular structures.
Two additional rare types of oculocutaneous albinism with important systemic findings and an increased risk of mortality are Hermansky-Pudlak syndrome and Chediak-Higashi syndrome.
Ocular albinism type I is an X-linked disorder associated with the OA1 gene. Type I is the most common form of ocular albinism. Female carriers can show minor signs, whereas males with ocular albinism can show a constellation of any of the above-mentioned findings.
The visual acuity in patients with albinism is variable and ranges from 20/40 to 20/400. [3, 4]
Melanin is the pigment responsible for skin, hair, and eye coloration. Albinism is caused by a disorder of melanin metabolism, and the defect can lie with either melanin synthesis or distribution. Melanin is synthesized in melanocytes from the amino acid tyrosine. This process takes place in special organelles called melanosomes. The pathophysiology of oculocutaneous albinism involves a reduction in the amount of melanin present in each of the melanosomes. The pathophysiology of ocular albinism is a reduction in the number of melanosomes, although each melanosome may be fully pigmented.
The most important enzyme in the synthesis of melanin is tyrosinase, which converts tyrosine to dopa. The gene for the enzyme tyrosinase has been localized to chromosome 11. A number of mutations have been found at this locus, which can result in an absent or defective tyrosinase enzyme. This results in type I oculocutaneous albinism, which is characterized by complete absence of skin and eye pigmentation, despite a normal number of melanosomes.
In contrast, the type II (tyrosine positive) oculocutaneous albinism defect is within the P polypeptide, which is a melanosomal tyrosine transporter. The P gene has been mapped to chromosome 15 and is more commonly linked with albinism in patients of African descent. These patients do have some pigment, but they have lighter pigmentation than expected due to their relatives and ethnicity.
Ocular albinism type I is an X-linked disorder related to defects in the OA1 gene. This gene produces pigment cell-specific, intracellular G-protein coupled receptor 143 (GPR143), [5] which appears to result in faulty transport of melanosomes and lysosomes as well as macromelanosomes. Patients with this disorder are found to have giant melanosomes in their skin melanocytes and retinal pigment epithelium.
The exact mechanism by which the absence of pigmentation leads to foveal hypoplasia and abnormal decussation of optic nerve fibers is not completely understood. It has been postulated that retinal pigment epithelial pigmentation around the macula is necessary for the normal development of the fovea. It also has been suggested that the absence of dopa, which is an antimitotic agent, can influence normal retinal development. This foveal hypoplasia is responsible for some degree of decreased visual acuity in almost all types of albinism. The abnormal decussation of optic nerve fibers is responsible for strabismus and monocular vision. Photophobia results from iris transillumination defects.
United States
The frequency of type I (tyrosinase negative) oculocutaneous albinism is approximately 1 in 17,000 to 1 in 20,000.
The frequency of type IB albinism appears to be higher among Amish people.
The frequency of type II (tyrosinase positive) oculocutaneous albinism is higher in the African American population, where it can be 1 in 10,000, as compared to 1 in 36,000 in Caucasian Americans.
The prevalence of X-linked ocular albinism is estimated to be 1 in 50,000.
International
The frequency of type I oculocutaneous albinism worldwide is about the same as in the United States.
The frequency of type II oculocutaneous albinism is higher in African countries, where it can range from 1 in 2000 to 1 in 5000.
Similarly, the frequency of Hermansky-Pudlak syndrome is much higher in Puerto Rico, where it is approximately 1 in 2700.
The main cause for morbidity in patients with albinism is decreased visual acuity.
In tropical regions, there can be higher mortality among these patients secondary to an increased incidence of skin cancer due to sun exposure.
Mortality also is increased in patients with Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. Patients with Hermansky-Pudlak syndrome have a bleeding diathesis secondary to platelet dysfunction and also experience restrictive lung disease, inflammatory bowel disease, cardiomyopathy, and renal disease. Patients with Chediak-Higashi syndrome are susceptible to infection and also can develop lymphofollicular malignancy.
Albinism affects all racial groups. However, type II oculocutaneous albinism occurs more frequently in African American and African populations. Similarly, there is a much higher incidence of Hermansky-Pudlak syndrome among people of Puerto Rican origin.
Oculocutaneous albinism affects both sexes equally. Ocular albinism is a disease primarily of males because of its sex-linked transmission.
Most people with albinism are diagnosed during infancy or early childhood.
Visual prognosis in patients with albinism is quite variable. Usually, no improvement in visual acuity occurs in patients with type I oculocutaneous albinism. Visual acuity may improve with increased pigmentation in other forms of albinism as the patient grows older.
Garrod AE. Inborn errors of metabolism. Lecture II. Lancet. 1908. 2:73-79.
Giordano F, Simoes S, Raposo G. The ocular albinism type 1 (OA1) GPCR is ubiquitinated and its traffic requires endosomal sorting complex responsible for transport (ESCRT) function. Proc Natl Acad Sci U S A. 2011 Jul 19. 108(29):11906-11. [Medline]. [Full Text].
Dijkstal JM, Cooley SS, Holleschau AM, King RA, Summers CG. Change in Visual Acuity in Albinism in the Early School Years. J Pediatr Ophthalmol Strabismus. 2011 Jul 6. 1-6. [Medline].
Merrill K, Hogue K, Downes S, Holleschau AM, Kutzbach BR, MacDonald JT, et al. Reading acuity in albinism: evaluation with MNREAD charts. J AAPOS. 2011 Feb. 15(1):29-32. [Medline].
De Filippo E, Schiedel AC, Manga P. Interaction between G Protein-Coupled Receptor 143 and Tyrosinase: Implications for Understanding Ocular Albinism Type 1. J Invest Dermatol. 2017 Feb. 137 (2):457-465. [Medline].
McCafferty BK, Wilk MA, McAllister JT, Stepien KE, Dubis AM, Brilliant MH, et al. Clinical Insights Into Foveal Morphology in Albinism. J Pediatr Ophthalmol Strabismus. 2015 May-Jun. 52 (3):167-72. [Medline].
Filloux FM, Hoffman RO, Viskochil DH, Jungbluth H, Creel DJ. Ophthalmologic features of Vici syndrome. J Pediatr Ophthalmol Strabismus. 2014 Jul 1. 51 (4):214-20. [Medline].
Seo JH, Yu YS, Kim JH, et al. Correlation of visual acuity with foveal hypoplasia grading by optical coherence tomography in albinism. Ophthalmology. 2007 Aug. 114(8):1547-51. [Medline].
Rossi S, Testa F, Gargiulo A, Di Iorio V, Pierri RB, D’Alterio FM, et al. The role of optical coherence tomography in an atypical case of oculocutaneous albinism: a case report. Case Rep Ophthalmol. 2012 Jan. 3(1):113-7. [Medline]. [Full Text].
Meyer CH, Lapolice DJ, Freedman SF. Foveal hypoplasia in oculocutaneous albinism demonstrated by optical coherence tomography. Am J Ophthalmol. 2002 Mar. 133(3):409-10. [Medline].
Sepúlveda-Vázquez HE, Villanueva-Mendoza C, Zenteno JC, Villegas-Ruiz V, Pelcastre-Luna E, García-Aguirre G. Macular optical coherence tomography findings and GPR143 mutations in patients with ocular albinism. Int Ophthalmol. 2014 Oct. 34 (5):1075-81. [Medline].
Sheth V, Gottlob I, Mohammad S, McLean RJ, Maconachie GD, Kumar A, et al. Diagnostic Potential of Iris Cross-sectional Imaging in Albinism Using Optical Coherence Tomography. Ophthalmology. 2013 May 29. [Medline].
Cornish KS, Reddy AR, McBain VA. Concentric macular rings sign in patients with foveal hypoplasia. JAMA Ophthalmol. 2014 Sep. 132 (9):1084-8. [Medline].
Prins D, Hanekamp S, Cornelissen FW. Structural brain MRI studies in eye diseases: are they clinically relevant? A review of current findings. Acta Ophthalmol. 2015 Sep 11. [Medline].
Mohammad S, Gottlob I, Sheth V, Pilat A, Lee H, Pollheimer E, et al. Characterization of Abnormal Optic Nerve Head Morphology in Albinism Using Optical Coherence Tomography. Invest Ophthalmol Vis Sci. 2015 Jul. 56 (8):4611-8. [Medline].
Schulze Schwering M, Kumar N, Bohrmann D, Msukwa G, Kalua K, Kayange P, et al. Refractive errors, visual impairment, and the use of low-vision devices in albinism in Malawi. Graefes Arch Clin Exp Ophthalmol. 2015 Apr. 253 (4):655-61. [Medline].
Sinha MK, Chhablani J, Shah BS, Narayanan R, Jalali S. Surgical challenges and outcomes of rhegmatogenous retinal detachment in albinism. Eye (Lond). 2016 Mar. 30 (3):422-5. [Medline].
Farahi A, Hashemi H, Mehravaran S. Combined cataract surgery and aniridia ring implantation in oculocutaneous albinism. J Cataract Refract Surg. 2015 Nov. 41 (11):2438-43. [Medline].
Abadi R, Pascal E. The recognition and management of albinism. Ophthalmic Physiol Opt. 1989 Jan. 9(1):3-15. [Medline].
Carden SM, Boissy RE, Schoettker PJ, et al. Albinism: modern molecular diagnosis. Br J Ophthalmol. 1998 Feb. 82(2):189-95. [Medline].
Creel D. Problems of ocular miswiring in albinism, Duane’s syndrome, and Marcus Gunn phenomenon. Int Ophthalmol Clin. 1984 Spring. 24(1):165-76. [Medline].
Creel D, Witkop CJ Jr, King RA. Asymmetric visually evoked potentials in human albinos: evidence for visual system anomalies. Invest Ophthalmol. 1974 Jun. 13(6):430-40. [Medline].
Creel DJ, Summers CG, King RA. Visual anomalies associated with albinism. Ophthalmic Paediatr Genet. 1990 Sep. 11(3):193-200. [Medline].
Davis PL, Baker RS, Piccione RJ. Large recession nystagmus surgery in albinos: effect on acuity. J Pediatr Ophthalmol Strabismus. 1997 Sep-Oct. 34(5):279-83; discussion 283-5. [Medline].
François J. Albinism. Ophthalmologica. 1979. 178(1-2):19-31. [Medline].
Garner A, Jay BS. Macromelanosomes in X-linked ocular albinism. Histopathology. 1980 May. 4(3):243-54. [Medline].
Hermansky F, Pudlak P. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies. Blood. 1959 Feb. 14(2):162-9. [Medline].
Ilia M, Jeffery G. Retinal mitosis is regulated by dopa, a melanin precursor that may influence the time at which cells exit the cell cycle: analysis of patterns of cell production in pigmented and albino retinae. J Comp Neurol. 1999 Mar 15. 405(3):394-405. [Medline].
Jeffery G. The retinal pigment epithelium as a developmental regulator of the neural retina. Eye. 1998. 12 (Pt 3b):499-503. [Medline].
Jeffery G, Schutz G, Montoliu L. Correction of abnormal retinal pathways found with albinism by introduction of a functional tyrosinase gene in transgenic mice. Dev Biol. 1994 Dec. 166(2):460-4. [Medline].
Kerr R, Stevens G, Manga P, et al. Identification of P gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa. Hum Mutat. 2000. 15(2):166-72. [Medline].
King RA, Hearing VJ, Creel DJ. Albinism. Scriver CR, Beauder AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York: McGraw Hill; 1995. 4353-92.
Kinnear PE, Jay B, Witkop CJ Jr. Albinism. Surv Ophthalmol. 1985 Sep-Oct. 30(2):75-101. [Medline].
Kriss A, Russell-Eggitt I, Harris CM, et al. Aspects of albinism. Ophthalmic Paediatr Genet. 1992 Jun. 13(2):89-100. [Medline].
Lyle WM, Sangster JO, Williams TD. Albinism: an update and review of the literature. J Am Optom Assoc. 1997 Oct. 68(10):623-45. [Medline].
O’Donnell FE Jr, Green WR, Fleischman JA, et al. X-linked ocular albinism in Blacks. Ocular albinism cum pigmento. Arch Ophthalmol. 1978 Jul. 96(7):1189-92. [Medline].
Oetting WS. Albinism. Curr Opin Pediatr. 1999 Dec. 11(6):565-71. [Medline].
Oetting WS, Brilliant MH, King RA. The clinical spectrum of albinism in humans. Mol Med Today. 1996 Aug. 2(8):330-5. [Medline].
Oetting WS, King RA. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat. 1999. 13(2):99-115. [Medline].
Oetting WS, Summers CG, King RA. Albinism and the associated ocular defects. Metab Pediatr Syst Ophthalmol. 1994. 17(1-4):5-9. [Medline].
Palmisano I, Bagnato P, Palmigiano A, Innamorati G, Rotondo G, Altimare D, et al. The ocular albinism type 1 (OA1) protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells. Hum Mol Genet. 2008 Aug 18. [Medline].
Schiaffino MV, Tacchetti C. The ocular albinism type 1 (OA1) protein and the evidence for an intracellular signal transduction system involved in melanosome biogenesis. Pigment Cell Res. 2005 Aug. 18(4):227-33. [Medline].
Smith SA, Wong PK, Jan JE. Unilateral alpha reactivity: an electroencephalographic finding in albinism. J Clin Neurophysiol. 1998 Mar. 15(2):146-9. [Medline].
Spritz RA. Molecular genetics of oculocutaneous albinism. Hum Mol Genet. 1994. 3 Spec No:1469-75. [Medline].
Summers CG, Knobloch WH, Witkop CJ Jr, et al. Hermansky-Pudlak syndrome. Ophthalmic findings. Ophthalmology. 1988 Apr. 95(4):545-54. [Medline].
Weleber RG, Pillers DA, Powell BR, et al. Aland Island eye disease (Forsius-Eriksson syndrome) associated with contiguous deletion syndrome at Xp21. Similarity to incomplete congenital stationary night blindness. Arch Ophthalmol. 1989 Aug. 107(8):1170-9. [Medline].
Witkop CJ Jr, White JG, Nance WE, et al. Classification of albinism in man. Birth Defects Orig Artic Ser. 1971 Jun. 7(8):13-25. [Medline].
Mohammed O Peracha, MD Associate Physician, Midwest Eye Center
Mohammed O Peracha, MD is a member of the following medical societies: American Academy of Ophthalmology
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Frances M Cosgrove, MD Resident Physician, Department of Ophthalmology, Indiana University School of Medicine
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Enrique Garcia-Valenzuela, MD, PhD Clinical Assistant Professor, Department of Ophthalmology, University of Illinois Eye and Ear Infirmary; Consulting Staff, Vitreo-Retinal Surgery, Midwest Retina Consultants, SC, Parkside Center
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Dean Eliott, MD Associate Director, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School
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Ocular Manifestations of Albinism
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