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Albinism

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Albinism

Introduction

Albinism is a group of heritable conditions that primarily affect the ectodermal-derived

tissues of the body, where there is a relative decrease or absence of melanin pigment. The present

is more commonly known as oculocutaneous albinism (OCA), which means that the condition

phenotypically manifests in the eyes and the skin (Cleveland Clinic, 2021; MedlinePlus

Genetics, 2020). OCAs can either be isolated, syndromic, or non-syndromic (Mayo Clinic,

2018). Specifically, the isolated form is known as isolated ocular albinism (OA1); the syndromic

variants include Hermansky-Pudlak syndrome (HPS), Chediak-Higashi syndrome (CHS),

Angelman (AS) and Prader-Willi (PWS) syndromes. The non-syndromic variants that have been

identified are seven in number so far and are systematically arranged from OCA1 to OCA7

(Cleveland Clinic, 2021).

Generally, albinism occurs due to detective melanocytes that have undergone a genetic

point mutation leading to decreased melanin synthesis, particularly within the dermal tissues

(MedlinePlus Genetics, 2020). Epidemiologically, the occurrence rates within the global

population stand at 1:17,000 to 1:20,000 (MedlinePlus Genetics, 2020). The most common

mutation is the OCA2 nutation, which is prevalent in sub-Saharan Africa at 1:39,000; however,

in the U.S., the prevalence of OCA1 is 1:36,000, the most common form of albinism

(MedlinePlus Genetics, 2020).

Genetics of Albinism

The melanocyte population within the epidermal basal layer range from 5% to 10% of the

total number of cells in the layer (Genetic and Rare Diseases Information Center (GARD),
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2016). Therefore, in albinism, this number remains unaffected; the disparity arises from the

dysfunctional synthesis of the forms of melanin within melanocytes (Genetic and Rare Diseases

Information Center (GARD), 2016). Depending on differing conditions of OCA, syndromic

albinism, and selected albinism-associated disorders, albinism has differing genotypes relating to

point mutations that mediate melanin production within melanocytes (Genetic and Rare Diseases

Information Center (GARD), 2016).

Among the non-syndromic variants of albinism, most of them have an identifiable gene

mutation except the OCA5 variant (Genetic and Rare Diseases Information Center (GARD),

2016). However, all the variants are transmitted in an autosomal recessive manner. For instance,

OCA1 is affected through the TYR gene, which produces tyrosinase that hydroxylates L-tyrosine

to L-DOPA and oxidates L-DOPA to DOPAquinone (Genetic and Rare Diseases Information

Center (GARD), 2016). Failure to produce the enzyme results in decreased or absent melanin

production. Additionally, OCA2 is due to aberrations in the OCA2 gene, which is OCA2

melanosome transmembrane protein P, whose function is currently unknown. OCA3, OCA4,

OCA6 and OCA7 result from aberrations in the genes TYRP1, SLC45A2, SLC24A5, and LRMDA

genes, respectively (Genetic and Rare Diseases Information Center (GARD), 2016).

The syndromic variants HPS and CHS are transmitted in an autosomal recessive manner.

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) occur due to spontaneous partial

deletions of chromosome 15q; therefore, they are non-heritable (Genetic and Rare Diseases

Information Center (GARD), 2016). Ocular albinism (OA1) results from an X-linked mutation of

the GPR143 gene that leads to the dysfunctional biogenesis of melanosomes within melanocytes.
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The autosomal recessive variants, for instance, HPS, has ten different genotypes that

correspond to their clinical subtypes, which include the HPS1 gene (HPS1), AP3B1 gene

(HPS2), HPS3 gene (HPS3), HPS4 gene (HPS4), HPS5 gene (HPS5), HPS6 gene

(HPS6), DTNBP1 gene (HPS7), BLOC1S3 gene (HPS8), BLOC1S6 gene (PLDN), AP3D1 gene

(HPS10) (Genetic and Rare Diseases Information Center (GARD), 2016). Aside from their

phenotypical expression of albinism, the subtypes are associated with other pathological variants;

for example, the most severe forms, both HPS1 and HPS4, are strongly associated with early-

onset idiopathic pulmonary fibrosis and granulomatous colitis (Genetic and Rare Diseases

Information Center (GARD), 2016). Conversely, CHS is due to aberrations in the LYST gene,

leading to diminished chemotaxis in leucocytes and platelets (Genetic and Rare Diseases

Information Center (GARD), 2016). Aside from the characteristic hypomelanosis associated with

the syndrome, it is characterized by increased incidences of pyogenic infections, neutropenia,

peripheral neuropathy, and mild coagulopathy (Genetic and Rare Diseases Information Center

(GARD), 2016).

Symptomatology of Albinism

The symptoms of albinism vary depending on the specific genetic aberration associated

with or based on the associated syndromes. The classic presentation of albinism is seen in the

form of white hair, white eyelashes, white skin, and pink eyes (Mayo Clinic, 2018). However,

due to residual pigmentation seen in varying states of albinism, some pigmentation can develop

with the age of the patient use of sunscreen, shampoos, and other cosmetic products.

Phenotypically, it is more challenging to distinguish albinism in the Caucasian populations,

particularly patients with a relatively higher expression of pheomelanin to eumelanin ratios

(Cleveland Clinic, 2021).

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The most debilitating symptoms are the ocular findings which include photophobia,

refractive errors, foveal hyperplasia, nystagmus, strabismus, stereopsis, reduced iris

pigmentation, and yellow or orange retina (Mayo Clinic, 2018). In the US, the most common

phenotype of the OCA1 type of albinism is divided into a type A and Type B form. Type A

forms present commonly due to the absence of melanin; the patients typically present with white

skin and white hair, which is the primary cutaneous manifestation. An ocular manifestation of

the type A form of OCA1, pink, red, or lightly colored irides in ambient light, nystagmus, foveal

hypoplasia, and photophobia. The visual acuity among individuals in this group range from

20/100 to 20/400. Conversely, type B OCA1 is due to a residual functioning of the TYR gene;

therefore, the patient demonstrates partial melaninization of skin and hair by three years, with a

partial tan or cream color. The irides are either blue, green, hazel, or light brown. Their visual

acuity ranges from 20/100 to 20/200.

Management of Albinism

In the management of albinism as a condition, it’s prudent to address some of the

causative mechanisms involved in the development of other complications. Chiefly, patients with

albinism must protect themselves from ultraviolet (UV) radiation from sun exposure or through

tanning beds (Health Direct, 2019). Therefore, such patients must apply sunscreen on their skin,

especially on potentially sun-exposed areas. The recommended sun protective factor (SPF) of 20

is desired; however, SPF above 50 is ideal if available (Health Direct, 2019). Additionally,

wearing wide-brimmed hats, long-sleeved clothes, and protective sunglasses to cover areas of

skin is also ideal (Health Direct, 2019). Moreover, the patients need to be educated on skincare

and self-examination to detect skin lesions to limit the occerence1 of squamous cell carcinomas

and malignant melanomas.

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Regarding eye abnormalities, refractive errors in vision can be managed using

prescription corrective lenses with UV protection. Teaching and visual aids should be provided

to assist such patients in reading to limit educational delays due to visual deficits (Health Direct,

2019). Non- refractive errors tend to resolve with age; however, severe forms may benefit from

corrective surgery of the extraocular muscles. Finally, patients may benefit from genetic

counseling when they desire to have children. Specifically, albinism is an obligate homozygote

condition where its transmission is almost 100%. Genetic testing of both partners is critical,

regardless of one being unaffected by the condition. Transmission of the defective gene is

possible when both partners have the same pathogenic variant of OCA, or they are obligate

carriers. A couple with an albino child has a 25% chance of having an albino child and a 50%

chance that the resulting children may be carriers as shown in Figure 1. There is a 25% chance

that the children will be non-carrier offspring; this will happen if one of the partners does not

have albinism. Suppose both are albino the chances of producing a second albino child after a

confirmed albino offspring is 50% (Figure 1). Additional concerns during genetic counseling are

that non-albino children have a 67% chance of being carriers of the albinism trait.
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References

Cleveland Clinic. (2021, August 5). Albinism: Types, Symptoms and Causes. Cleveland Clinic.

https://my.clevelandclinic.org/health/diseases/21747-albinism

Genetic and Rare Diseases Information Center (GARD). (2016). Albinism | Genetic and Rare

Diseases Information Center (GARD) – an NCATS Program. Nih.gov.

https://rarediseases.info.nih.gov/diseases/5768/albinism

Health Direct. (2019, November 24). Albinism. Healthdirect.gov.au; Healthdirect Australia.

https://www.healthdirect.gov.au/albinism

Mayo Clinic. (2018, April 7). Albinism - Symptoms and causes. Mayo Clinic.

https://www.mayoclinic.org/diseases-conditions/albinism/symptoms-causes/syc-

20369184

MedlinePlus Genetics. (2020, August 18). Oculocutaneous albinism: MedlinePlus Genetics.

Medlineplus.gov. https://medlineplus.gov/genetics/condition/oculocutaneous-albinism/
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Appendix

Figure 1

An Inheritance Pedigree Chart for Albinism