Albinism

Last updated: 1 February 2010.

Introduction

AlbinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information is an inherited genetic condition that occurs when the body is unable to produce or distribute melaninMelanin is a naturally produced polymer found in a multitude of locations in the body, from the eye and ear, to the brain and skin. Click here for more information., our own body’s pigment. The resulting lack of pigment in the skin, hair and eyes is characteristic of albinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information. AlbinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information can be classified into oculocutaneous albinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information (OCA) types 1, 2, 3 and 4, ocular albinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information (OA), Chediak-Higashi Syndrome (CHS), Hermansky-Pudlak Syndrome (HPS), and Griscelli Syndrome (GS). CHS and HPS have extra-pigmentary effects on the components of the blood, such as clotting cells and immune cells. GS affects the immune system and nerves.

Incidence

The different sub-types of albinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information have different incidences and they range from 1 in 15,000 individuals for OCA type 2 to 1 in 50,000 for OA. The syndromic forms of albinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information (i.e. CHS, HPS and GS) are extremely rare.

Causes

Genetic defects that cause a lack of, or little, production or distribution of melaninMelanin is a naturally produced polymer found in a multitude of locations in the body, from the eye and ear, to the brain and skin. Click here for more information. result in the manifestation of albinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information. AlbinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information can be passed down through families. Individuals can carry a defective gene mutation without being albinistic – i.e. they are ‘carriers’. A child has an increased risk of being albinistic, if both parents are carriers of a defective gene mutation.

Symptoms

Depending on the sub-type of albinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information, the disorder can manifest as:

• Complete absence of colouring on the skin, eyes and hair; or
• Partial absence of colouring on the skin and hair; or
• Areas of absence of colouring – i.e. ‘patchy’ skin.

Several sub-types of albinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information results in visual disorders including:

• Crossed eyes (strabismus);
• Rapid eye movements (nystagmus);
• Sensitivity to light (photophobia); and/or
• Impaired vision (can be severe enough in individuals to be deemed legally blind).

AlbinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information is diagnosed through genetic testing. The appearance of skin, eyes and hair at birth may also aid in diagnosis.

Treatments

AlbinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information cannot be cured and treatments are aimed at managing the symptoms. Avoiding sun exposure and the use of broad-spectrum sunscreens may help prevent skin damage. Individuals with albinismAlbinism is an inherited genetic condition that occurs when the body is unable to produce or distribute melanin, our own body’s pigment. Click here for more information, particularly those with OCA, should be reviewed for skin cancers on a regular basis. Genetic counselling should be offered, to parents of affected infants, on ways to manage the disorder. Visual problems may require corrective lenses or surgery. Referral to a low-vision clinic is also an option.

Introduction

Albinism encompasses a number of genetic disorders that affect the melanin system. Albinism can be classified into oculocutaneous albinism (OCA) types 1, 2, 3 and 4, ocular albinism (OA), Chediak-Higashi Syndrome (CHS), Hermansky-Pudlak Syndrome (HPS), and Griscelli Syndrome (GS). CHS and HPS have extra-pigmentary effects on platelets and lymphocytes. GS affects the immune and the nervous system. Each sub-type of albinism involves a genetic mutation on a different chromosome. The hypopigmentation that is characteristic of albinism ranges from complete absence of melanin to minimal reduction in skin and hair colour for the different sub-types. On the other hand, the visual disorders that result from the different sub-types of albinism are essentially constant.

Epidemiology and prevalence

Oculocutaneous albinism (OCA) comprises a heterogeneous group of autosomal recessive disorders. Melanin is either absent or present at reduced levels in these conditions. The incidences of the different sub-types of OCA are:

• 1 in 40,000 individuals for OCA type 1
• 1 in 15,000 individuals for OCA type 2 (found at higher rates in African populations)
• 1 in 8,500 individuals for OCA type 3 (occurs almost exclusively in African populations)
• OCA type 4 is rare except in Japanese populations, where 18% of individuals with OCA are afflicted by this sub-type.

Ocular albinism (OA) is characterised by normal or near-normal pigmentation of the skin and hair, but an absence of melanin in the eyes. About 1 in 50,000 individuals are affected by this condition. OA is inherited as a X-linked recessive disorder and hence, predominates in males.

The syndromic forms of albinism (i.e. CHS, HPS and GS) are extremely rare in the general population.

With the exceptions discussed above, all races and both sexes are equally affected by albinism

Clinical features

All sub-types of OCA and OA have similar optical findings. These include:

• Varying degrees of nystagmus;
• Iris translucency due to hypopigmentation;
• Hypopigmentation of the retinal epithelia;
• Foveal hypoplasia;
• Reduced visual acuity;
• Refractive disorders;
• Strabismus;
• Photophobia; or
• Reduced stereoscopic vision.

Misrouting of the optic nerves, as demonstrated by monocular visual evoked potential, is characterised by excessive crossing of optic fibres at the optic chiasma. Absence of misrouting excludes the diagnosis of albinism.

For skin and hair hypopigmentation, the different sub-types exhibit different phenotypes as discussed below:

• OCA type 1 is further classified into types 1A and 1B. In type 1A, the hair and skin are white and the skin does not tan. The irises are fully translucent and appear light blue or almost pink. Photophobia is severe and visual acuity is poor (1/10). In type 1B, skin and hair pigmentation may develop with time. Cooler areas of the body, such as the hands and feet, may develop pigmented hairs. Visual acuity is poor (2/10).
• In OCA type 2, the amount of skin pigmentation varies. The hair is almost always pigmented, however, and naevi and pigmented freckles can develop over time. Visual acuity is about 3/10.
• In OCA type 3, patients have red hair and reddish-brown skin. Visual anomalies in this group are rare.
• In OCA type 4, the manifestations are phenotypically similar to that of OCA type 2.

In OA, cutaneous hypopigmentation is not apparent. The visual anomalies, as discussed above, do occur.

The syndromic forms of albinism are not due to defects in the melanin pathway per se, but manifest due to dysfunction of organelles, such as melanosomes or lysosomes. As a result, albinism occurs along with other extra-pigmentary disorders such as immune and neurological defects. Furthermore, there are other congenital hypopigmentation disorders, such as Waardenburg syndrome, which resemble albinism but are distinct clinical entities.

Aetiology and pathogenesis

Embryologically, melanocytes are derived from the neural crest and these cells migrate to the skin, brain, inner ear, uveal tract, iris stroma, ciliary stroma and choroid. The amino acid tyrosine is converted to melanin in a sequence of biochemical reactions. A number of enzymes and associated regulatory proteins catalyse these biochemical reactions. Within the melanocytes are organelles called melanosomes into which the melanin pigment is contained. In the skin, the melanosomes are transferred to the surrounding keratinocytes.

Albinism is caused by one or more mutations in the genes involved in melanin biosynthesis. In OCA type 1, mutations in the tyrosinase (TYR) gene on chromosome 11q14.3 cause degradation of the enzyme tyrosinase. Consequently, melanin synthesis does not occur or occurs to a limited extent.

In OCA type 2, mutations in the OCA2 gene (also known as the P gene) affects its protein product, an integral melanosomal protein. This protein is important in the transport of other melanosomal proteins and is involved in the normal biogenesis of melanin. Located on chromosome 15q11.2-q12, over 75 mutations have been reported in the OCA2 gene.

In OCA type 3, mutations in the tyrosine-related protein 1 (TYRP1) gene, which is located on chromosome 9p23, causes a delayed maturation and early degradation of tyrosine, the precursor of melanin.

In OCA type 4, mutations in the membrane-associated transport protein (MATP) gene, which is located on chromosome 5p13.3, affects pigmentation. The precise function of the protein product is unknown but it has been postulated that MATP functions as a membrane transporter in melanosomes.

OA is inherited as an X-linked recessive trait. The OA gene is located on chromosome Xp22.3. The function of the protein product is unknown.

CHS, HPS and GS are inherited in an autosomal-recessive fashion and the mutations involved affect trafficking of melanosomes and other cell systems.

The impairment of vision seen in albinism is due to a multitude of factors. As a result of foveal hypoplasia, the central cones are spaced apart leading to impaired central acuity. Intraocular light scatter also plays a role in reduced visual acuity. The misrouting of optic fibres is thought to play a role in reduced stereoscopic vision. Reduced levels of melanin lead to defects in neuronal migration in the visual system via complex interactions between ganglion cells and optic chiasm embryonic neurons.

Diagnosis

Albinism is diagnosed based on clinical findings of hypopigmentation of the skin and hair as well as the visual defects described above. In order to distinguish between the different subtypes, however, molecular genetic testing is required. Genetic testing of the TYR and OCA2 genes are now available clinically. Analysis of TYRP1 and MATM are available only in specialized research laboratories and, therefore, not performed routinely. Diagnosis of OA is carried out by performing a skin biopsy, to check for macromelanosomes in the epidermis, on female family members to check for carrier status. For CHS, silver-coloured hair and the presence of neutrophils with large inclusions on a blood smear confirms diagnosis. Individuals with HPS, on the other hand, would be expected to have minimal to moderate hypopigmentation and reduced blood-clotting upon testing. For GS, immunological testing and testing for neurological abnormalities is indicative of the disease. It should be noted that these investigations are not routine clinical tests and are not usually performed unless clinically warranted.

Prevention

Albinism is a genetic condition and cannot be prevented or cured. The symptoms can be managed or controlled and precautions can be taken to avoid exacerbations, as discussed in the ‘Treatments’ section below.

Treatments

Parents of affected infants should be offered genetic counselling. Avoiding sun exposure and the use of broad-spectrum and high-protection sunscreen is recommended. Visual problems can be improved through corrective lenses or surgery. Photophobia can be helped with dark glasses. At school, children may be offered large-print textbooks and magnifiers for computer use. Referral to a low-vision clinic may be necessary.

Prognosis

Patients with OCA have a normal lifespan. However, because of their increased risk of developing skin cancers, they should be offered regular follow-ups to check for neoplasms. It should be noted that patients with OCA may be restricted in their activities because of their increased risk of sun-induced damage and photophobia. Patients with OCA and OA are also afflicted by visual disorders, which may reduce their quality of life. Contrary to common misconceptions, these patients have normal intelligence and normal fertility.

On the other hand, patients with the syndromic forms of albinism (CHS, HPS and GS) have a reduced lifespan. CHS and GS patients usually die in the first decade of life due to bleeding disorders and chronic infections respectively. HPS proves fatal in the fifth decade of life due to pulmonary fibrosis and cardiomyopathy. As can be inferred, the syndromic forms of albinism are fatal due to extra-pigmentary and extra-cutaneous effects, rather than hypopigmentation per se. Patients with these syndromes, therefore, require regular clinical review to check for progression of these extra-pigmentary disorders.

References

• Carden, S M, Boissy, R E, Schoettker, P J & Good, W V (1998). ‘Albinism: modern molecular diagnosis’. British Journal of Opthalmology, Vol 82, pp. 189-195.
  
• emedicine.com (2008) Albinism. [Online]. Available online [Accessed 27/11/2008].
• Gronskov, K, Ek, J & Brondum-Nielsen, K (2007). ‘Oculocutaneous Albinism’. Orphanet Journal of Rare Diseases, Vol 2(43).
• Lee, S, Nicholls, R D, Bundey, S, Laxova, R, Musarella, M, Spritz, R A (1994). ‘Mutations of the P Gene in Oculocutaneous Albinism, Ocular Albinism, and Prader-Willi Syndrome Plus Albinism’. The New England Journal of Medicine, Vol 330(8), pp. 529-534.
• nlm.nih.gov (2008) Albinism. [Online]. Available online [Accessed 27/11/2008].
• Scheinfeld, N S (2003). ‘Syndromic albinism: a review of genetics and phenotypes’. Dermatology Online Journal, Vol 9(5).
• Vancoillie, G, Lambert, J, Nayaert, J M (1999). ‘Melanocyte biology and its implications for the clinician’. European Journal of Dermatology, Vol 9(3), pp. 241-251.

Online resources:

• NCBI: Albinism – A comprehensive resource guide for people with albinism from the US government
• NOAH (USA) – National Organisation for Albinism and Hypopigmentation
• Information for parents of children and infants with albinism – from Vision Australia
  
• International Albinism Centre - University of Minnesota

Online associations:

• NOAH (USA) – National Organisation for Albinism and Hypopigmentation (USA)
• Albinism Fellowship (UK)
• Albinism Fellowship of Australia
• Albinism Trust (New Zealand)
• Australian Association for Parents of Vision Impaired
• ALBA
• Albinismo.org
• Albinizm.ru
• Hermansky-Pudlak Syndrome Network Inc