Albinism

Background
Albinism consists of a group of inherited abnormalities of melanin synthesis and are typically
characterized by a congenital reduction or absence of melanin pigment. Albinism results from
defective production of melanin from tyrosine through a complex pathway of metabolic reactions.
Several types of albinism are recognized. The phenotypic heterogeneity of albinism is due to the
different gene mutations affecting various points along the melanin pathway, resulting in varying
degrees of decreased melanin production. Additionally, associated developmental changes occur in
the optic system as a result from this hypopigmentation.
The ophthalmologist plays an important role in detecting albinism because most forms of albinism
present with ocular features as the primary morbidity. The changes to the optic system associated with
hypopigmentation include decreased visual acuity secondary to foveal hypoplasia and misrouting of
the optic nerves at the chiasm. Other features include photophobia, iris transillumination, nystagmus,
and pigment deficiency in the peripheral retina. These ocular changes are common to all types of
albinism.

Classification of albinism
Traditionally, albinism has been classified according to clinical phenotype, and the 2 main categories
are oculocutaneous albinism (OCA) and ocular albinism (OA).
The albinism subtypes were reclassified in 2009. With the availability of new molecular genetic
studies, the classification of albinism has shifted emphasis to genotype as opposed to phenotype
alone.[1] Hence, this has led to redefining existing phenotypic categories and the addition of new
subtypes based on specific genetic mutations. The following is a brief overview of the current
classification of albinism.
OCA is characterized by the reduction or absence of melanin in the skin, hair, and optic system
(including the eyes and optic nerves). The lack of skin pigment results in a pale skin appearance and
an increased risk of skin cancer. As shown in Table 1, OCA is divided further into several subtypes
based on the distinct genetic mutation.
Table 1. Oculocutaneous Albinism Types (Open Table in a new window)
OCA Subtypes

Gene Position

Affected Protein

OCA 1

11q14-21

Tyrosinase

15q11-13

P protein

9p23

Tyrosinase-related protein

OCA 1A (tyrosinase-negative OCA)

OCA 1B (yellow-mutant/Amish/
xanthous, temperature-sensitive)
OCA 1A/1B heterozygote
OCA 2

(tyrosinase-positive OCA, brown OCA)

OCA 3

OA is characterized by changes in the optic system only with no clinical difference in skin and hair
color. As shown in Table 2, two major disorders exist in this category, ocular albinism 1 (OA 1) and
autosomal recessive ocular albinism (AROA).
Table 2. Ocular Albinism Types (Open Table in a new window)
OA Subtypes

Gene Position

Affected Protein

OA 1 (X-linked recessive OA/Nettleshop-Falls

type)

X p22.3-22.2

The protein product of the OA 1 gene named OA 1 (and also identified as GPR143 in
GenBank)[2, 3]

AROA

Not a distinct
position

Tyrosinase in some cases;

P protein in some cases

Pathophysiology
Melanin is a photoprotective pigment in the skin that absorbs UV light from the sun, thereby preventing
skin damage. With sun exposure, the skin normally tans as a result of increased melanin pigment in
the skin. However, many albinos are sensitive to sunlight and develop a sunburn because of the lack
of melanin.
In addition to the skin, melanin is important to other areas of the body, such as the eyes and brain,
although the function in these areas is not currently known.

Melanin in the eye

The eye has 2 origins from which pigmented cells are derived, as follows:

The neuroectoderm of the primitive forebrain is the origin of melanocytes in the retinal pigment
epithelium, iris epithelium (anterior and posterior), and ciliary epithelium (outer pigmented and inner
nonpigmented).

The neural crest is the origin of melanocytes in the iris stroma, ciliary stroma, and choroid.
Melanoblasts from the neural crest migrate to the skin, inner ear, and uveal tract.
The presence of melanin during ocular development is important. The fovea fails to develop properly if
melanin is absent during development. Other areas of the retina develop normally regardless of the
presence of melanin. Additionally, neural connections between the retina and the brain are altered if
melanin in the retina is absent during development. The amount of pigment necessary for appropriate
ocular development is currently unknown. More research needs to be completed.

Melanin pathway
Melanin is formed in the melanosome organelle of the melanocyte. Melanocytes are found in the skin,
hair follicles, and pigmented tissues of the eye. The melanin pathway consists of a series of reactions
that converts tyrosine into 2 types of melanin, as follows: black-brown eumelanin and red-blond
pheomelanin. Genetic mutations affecting proteins/enzymes along this pathway inevitably result in
reduced melanin production.
Tyrosinase is the major enzyme (coded on chromosome 11) involved in the series of conversions to
form melanin from tyrosine. It is responsible for converting tyrosine to DOPA and then to dopaquinone.
Through a sequence of steps, dopaquinone subsequently is converted to either eumelanin or
pheomelanin. Mutation to the tyrosinase enzyme produces either OCA 1 or AROA.
Additionally, 2 other enzymes involved in the formation of eumelanin are tyrosinase-related protein 1
(TRP1; DHICA oxidase) and tyrosinase-related protein 2 (TRP2; dopachrome tautomerase). Both of
these enzymes are coded on chromosome 9. Mutation to the TRP1 gene causes OCA 3. Mutation to
the TRP2gene does not produce albinism.
Finally, P protein is a melanosomal membrane protein that is believed to be involved in the transport of
tyrosine prior to melanin synthesis. Mutation to this P gene produces OCA 2.

Pathogenesis of ocular features

The development of the optic system is highly dependent on the presence of melanin. If melanin is
absent or reduced, the ocular features appear. The mechanisms for these changes include the
following:

Abnormal decussation of optic nerve fibers is due to misrouting of the retinogeniculate

projections. It is postulated that melanin determines neuronal target specificity in the brain.
Therefore, when pigmentation is incomplete, the developing optic tracts almost completely cross at
the chiasm. In nonalbino persons, 45% of axons originating in the temporal half of the retina remain
uncrossed as they pass through the chiasm and project to the ipsilateral lateral geniculate nucleus.
Most of these fibers serve the central 20 of the temporal retina. However, in albino persons, most of

the fibers decussate at the chiasm and synapse in the contralateral lateral geniculate nucleus. This
leads to a predominance of monocular vision and decreased binocular depth perception.
Light scattering within the eye causes the sensation of photophobia and decreased visual
acuity. The translucent irides cause increased light to enter the eye, resulting in light scattering.
Patients typically have a supernormal electroretinography (ERG) recording.
Light-induced retinal damage has been postulated as a contributing mechanism to decreased
visual acuity. With increased light scattering, it has been proposed that light-generated free radicals
are responsible for nonthermal light damage to the retina. Additionally, it is believed that melanin may
play a protective role in reducing these free radicals.
Foveal hypoplasia is the most significant factor causing decreased visual acuity. The macula
lutea pigment is believed to be absent. Currently, the etiology of foveal hypoplasia is not completely
known; however, it may be due to the decreased melanin in the retinal pigment epithelium (RPE).
Congenital nystagmus usually occurs in the first 3 months of life and may lead to the
misdiagnosis of congenital motor nystagmus.
Light-induced subclinical damage to the corneal epithelium and its binding to the Bowman
membrane have been postulated as a contributing mechanism to the decreased adhesion of the
corneal epithelium in LASIK surgery, leading to a very high risk of epithelial abrasion during LASIK in
patients with albinism. Possibly, the increased light scattering produces light-generated free radicals
that are responsible for nonthermal light damage to the epithelial linking proteins. Additionally, it is
believed that melanin may play a protective role in reducing these free radicals.

Epidemiology
Frequency
United States
An estimated 1 in 17,000 people have one of the types of albinism. Approximately 18,000 people in
the United States have albinism.
OCA 1 occurs in approximately 1 in 40,000 individuals in most populations.
OCA 2 is the most common type of albinism and is especially frequent among African Americans and
Africans. The estimated frequency in African Americans is 1 case per 10,000 population, while in
whites, the frequency is 1 case per 36,000 population. The overall frequency is 1 case per 15,000
population across all races.
Hermansky-Pudlak syndrome (HPS) s the most common type of albinism in Puerto Rico, with a
frequency of 1 case per 2,700 population. This disorder is very rare in other parts of the world.

Mortality/Morbidity

Albinism is not associated with mortality. Lifespan is within normal limits. Because the
reduction of melanin in the hair, skin, and eyes should have no systemic effects, the general health of
a child and an adult with albinism is normal. The growth and intellectual development of a child with
albinism should be normal, with developmental milestones expected for age.
The morbidity associated with albinism pertains to visual impairment, skin photosensitivity, and
increased cutaneous cancer risk. Patients who have syndromes associated with albinism (eg, HPS)
may have hearing difficulties or abnormalities of blood clotting. Albinism also has social ramifications
because patients may feel alienated as a result of the difference in appearance from their families,
peers, and other members of their ethnic group.

Race

Albinism affects all persons of races.

Parents of most children with albinism have normal eye color for their ethnic background.
A high incidence of HPS exists among Puerto Ricans.

Sex

Both males and females can be affected. However, in OA 1 (X-linked recessive OA), males
are affected, while females are only carriers.

Age

All types of albinism are usually congenital.

History
Patients with more severe forms of albinism with cutaneous manifestations are easier for a physician
to diagnose compared with those with more subtle forms or those with ocular albinism. With respect to

ocular complaints, patients typically report decreased central vision and photophobia. Skin symptoms
include skin photosensitivity.
Search for a history of easy bruising, frequent nosebleeds, or bleeding after surgery or dental work. A
positive history may point in the direction of HPS. A history of frequent infections may be consistent
with Chediak-Higashi syndrome (CHS).
Inquire about a family history of albinism. Children with albinism tend to prefer reading with a head tilt
and usually hold reading material up close.
The following is a more detailed description of the different subtypes of albinism:

Oculocutaneous albinism
Oculocutaneous albinism 1
OCA 1 is a disorder that results from mutations to the tyrosinase gene found
on chromosome 11 (band 11q14-21). Several different types of mutations to the tyrosinase gene
(missense, nonsense, and frameshift) are responsible for producing the 2 types of OCA 1 (OCA
1A and OCA 1B). Mutations can result in either inactive/no tyrosine (null mutations) or in the
production of tyrosine enzyme that has reduced activity from normal (leaky mutations). Null
mutations produce OCA 1A, while leaky mutations result in OCA 1B.
An important distinguishing characteristic of OCA 1 is the presence of marked
hypopigmentation at birth. Most individuals with OCA 1 (especially OCA 1A) have white hair,
milky white skin, and blue irides at birth. The irides can be very light blue and translucent, such
that the whole iris appears pink or red in ambient or bright light. However, with age, the irides
usually become darker blue and may remain translucent or lightly pigmented, with reduced
translucency.
Oculocutaneous albinism 1A
OCA 1A (classic tyrosinase-negative OCA) is the most severe form of OCA. It
is caused by nonsense, frameshift, and missense mutations of the tyrosinase gene on
chromosome 11 (band 11q24). These null mutations produce completely inactive tyrosinase,
resulting in no melanin formation throughout the patient's life.
The typical phenotype is white hair and skin, with blue and translucent irides.
No pigmented lesions develop in the skin, although amelanotic nevi may be present. Because of
a lack of pigmentation, these patients have no tanning potential and are at risk for sunburn and
skin cancer. This phenotype is the same in all ethnic groups and in all ages. Visual acuity usually
is diminished to as low as 20/400. Photophobia and nystagmus tend to be the worst in this
subtype. Hair bulb incubation in tyrosinase is usually negative.
Oculocutaneous albinism 1B
OCA 1B (yellow mutant OCA, Amish albinism, xanthous albinism) is produced
by leaky mutations of the tyrosinase gene that result in reduced/residual enzyme activity. To date,
55 mutations to the tyrosinase gene have been found to cause OCA 1B. These different
mutations result in differing amounts of residual tyrosinase activity and are the primary reason for
the variation in pigmentation in individuals with OCA 1B.
The range in pigmentation can vary from very little cutaneous pigment to
nearly normal skin pigmentation. Occasionally, a moderate amount of residual activity can lead to
near normal skin pigmentation and the wrong diagnosis of ocular albinism. These patients
completely lack pigment at birth, which can cause difficulty in distinguishing it from OCA 1A.
However, because some tyrosinase activity is still present, individuals may show an increase in
skin, hair, and eye pigment with age and may tan with sun exposure.
Patients rapidly develop yellow hair pigment in the first few years of life and
then continue to slowly accumulate pigment, principally yellow-red pheomelanin, in the hair, eyes,
and skin. Interestingly, patients with OCA 1B tend to develop dark eyelashes, often darker than
the scalp hair. The irides can produce hazel or light brown pigment that sometimes is limited to
the inner third of the iris. Visual acuity may be 20/90 to 20/400 and may improve with age.
Pigmented nevi can develop, although most nevi are amelanotic. Hair bulb testing shows greatly
reduced activity of tyrosinase, though still present.
Temperature-sensitive albinism
Temperature-sensitive albinism is a subtype of OCA 1B. This type of OCA 1B
is caused by a mutation of the tyrosinase gene that produces a temperature-sensitive tyrosinase
enzyme.[4]Heat-sensitive tyrosinase has approximately 25% the activity of normal tyrosinase at
37C and improved activity at lower temperatures. The enzyme does not work at regular body
temperatures (axillary and scalp region) but functions in cooler areas of the body (arms and legs).
Therefore, because melanin synthesis occurs in cooler areas of the body, arm and leg hair

pigment is usually dark, while axillary and scalp hair remains white (occasionally developing a
yellow tint with time). Individuals are believed to have OCA 1A during the first few years of life,
with white hair and skin and blue eyes.
This may be because the temperature of the fetus is high, so the tyrosinase
has low activity, resulting in absent pigment. However, postnatally, the skin is cooler, and, with
time, body hair in the cooler areas of the body develops pigment, while the eyes remain blue and
the skin remains white and does not tan. The eyes are warmer than other areas of the skin;
therefore, they do not develop additional pigmentation.
Oculocutaneous albinism 2
OCA 2 (tyrosine-positive OCA) is the most prevalent type of albinism in all
races. This disorder is also autosomal recessive but coded on a different chromosome from OCA
1 (band 15q11-13). This mutated region also is deleted in Prader-Willi syndrome (PWS) and
Angelman syndrome (AS), accounting for the close linkage of OCA 2 to these syndromes.
In OCA 1, the genetic mutation affects the gene coding for tyrosinase;
however, the OCA 2 genetic mutation affects the gene coding for the P protein and tyrosinase is
normal. The human P gene located on band 15q11.2-q12 is the homologue of the mouse p locus
(mutation causes reduction of eumelanin, a black pigment in the mouse, causing the mouse pinkeyed dilution). It is postulated that this human P gene encodes for a melanosomal membrane
protein involved in the transport of tyrosine.[5]
The phenotypic spectrum of OCA 2 varies, ranging from absent pigmentation
to almost normal pigmentation. Even though the tyrosinase genes are normal, most type 2 albino
persons have no black pigment (eumelanin) in the skin, hair, or eyes at birth. As a result, pigment
is nearly absent at birth, sometimes making it indistinguishable from OCA 1. However,
pigmentation tends to develop with age. The exact mechanism of this delay in albinism is not
known. The intensity of pigment accumulation depends on the racial background of the patients.
As the child matures, the increased pigmentation also results in improved vision (20/100 to
20/40).
In whites with OCA 2, the amount of pigment at birth can vary substantially.
The hair can have a light yellow-blond color, or it may be darker with a darker blond-red color.
The normal delayed maturation of the pigment system can make it difficult to distinguish OCA 2
from OCA 1. The skin is white and does not tan. Iris color is blue-gray, and the degree of iris
translucency is proportional to the amount of pigment present. As the child ages, increased
pigmentation occurs with pigmented nevi and freckles developing in areas of repeated sun
exposure. The hair also may turn darker with age.
In African Americans and Africans, OCA 2 has a distinct phenotype. At birth,
the hair is usually yellow and tends to remain as such through life, although some darkening may
occur. The skin is white and has no tanning potential. The iris is blue-gray, and pigmented nevi
may develop in some individuals.
Brown OCA is part of the OCA 2 spectrum that is exclusive to Africans and
African Americans. It is speculated that this syndrome may arise from leaky mutations to the P
protein gene, resulting in reduced P protein activity. The hair and skin are light brown, and the
irides are gray. As time passes, the hair and irides may darken, while the skin color remains
mainly unchanged. The ocular features are characteristic, with punctate and radial iris
translucency and retinal hypopigmentation. Visual acuity ranges from 20/60 to 20/150.
Oculocutaneous albinism 3
OCA 3 (previously known as red/rufous OCA) is caused by a mutation to the
human gene coding for TRP-1. This protein is the product of the brown locus in the mouse. A
mutation at this position causes the fur to be brown rather than black. In humans, the formation of
TRP-1 is not fully understood. However, it acts as a regulatory protein in the production of black
melanin (eumelanin). With mutation, a subsequent dysregulation of tyrosinase occurs, and brown
pigment is synthesized instead of black pigment.
OCA 3 is autosomal recessive. The clinical phenotype in African patients is
light brown or reddish brown skin and hair, and blue-brown irides. The ocular features are not
fully consistent with the diagnosis of OCA because some do not have iris translucency,
nystagmus, strabismus, or foveal hypoplasia. No misrouting of the optic nerves has been
demonstrated by a visual-evoked potential, suggesting either that this is not a true type of
albinism or that the hypopigmentation is not sufficient to consistently alter optic nerve
development. The phenotype for whites and Asians is not known at this time.
Ocular albinism
Ocular albinism 1
OA 1 (X-linked recessive OA/Nettleshop-Falls type) involves the eyes only.
Patients with OA 1 have normal skin; however, it may be paler than first-degree relatives. Ocular

findings in OA 1 are similar to those of OCA, with decreased visual acuity, refractive error, fundus
hypopigmentation, absent foveal reflex, strabismus, iris translucency, and posterior embryotoxon
in 30% of patients (implying anterior segment dysgenesis). The presence of nystagmus
occasionally has led to the misdiagnosis of congenital motor nystagmus.
The OA 1 locus is Xp22.3. Because this disorder is X-linked recessive, only
males manifest the disease and females are carriers. Hence, males show the complete
phenotype, while female carriers can show a mud-splattered fundus with hypopigmented streaks
in the periphery and marked iris translucency.
The protein product of the OA1 gene, termed OA 1 (and also identified as
GPR143 in GenBank), is a pigment cellspecific membrane glycoprotein, displaying structural
and functional features of G protein-coupled receptors (GPCRs). However, in contrast to all other
previously characterized GPCRs, OA 1 is not localized to the plasma membrane but is targeted
to intracellular organelles, namely late endosomes/lysosomes and melanosomes. These unique
characteristics suggest that OA 1 represents the first example described so far of an exclusively
intracellular GPCR and regulates melanosome biogenesis by transducing signals from the
organelle lumen to the cytosol.[2, 3]
Skin biopsy in carriers and in individuals with OA 1 usually shows the
presence of macromelanosomes, which aids in the diagnosis of OA 1. It has been postulated that
the OA1 gene is a glycoprotein necessary for the maturation of melanosomes, because
macromelanosomes are formed when premelanosomes fail to separate from the endoplasmic
reticulumGolgi system.
Autosomal recessive ocular albinism
AROA was first described in the 1970s in a series of families in which children
of normally pigmented parents had ocular features of albinism but did not have any cutaneous
hypopigmentation.
AROA was classified as autosomal recessive because both males and
females were affected. However, it has been shown that AROA is not a distinct entity. In fact,
genetic analysis revealed that some of those diagnosed with AROA had either abnormalities of
the tyrosinase gene or the P gene. Of those previously diagnosed with AROA, 14% have a
mutation of the tyrosinase gene on chromosome 11, making them OCA 1, while 36% have an
abnormality of the P gene on chromosome 15, actually making them OCA 2. Fifty percent have
neither an abnormality of the tyrosinase gene nor the P gene.
Conditions with close linkage to albinism
Close linkage to OCA 2
PWS and AS are both caused by deletion to band 15q11-13, the same region
coding the P protein gene. In OCA 2, the P gene mutation is adjacent to the area commonly
deleted in PWS or AS. One percent of patients with PWS or AS has OCA 2. Both PWS and AS
are caused by the same chromosomal deletion, but there are 2 separate phenotypes because of
genomic imprinting. If the deletion occurs on the paternal band 15q11-13, then PWS results.
However, if the same mutation occurs on the maternally derived chromosome, AS occurs. The
cause of this is unknown.
AS is a developmental disorder characterized by developmental delay, severe
mental retardation, inappropriate laughter, hyperactivity, tongue protrusion, widely spaced teeth
microcephaly, hypotonia, and ataxia. PWS is a systemic disorder characterized by obesity,
hypotonia, hypogonadism, short stature, dysmorphic facial features, and intellectual impairment.
Close linkage to OA 1: X-linked ichthyosis, Kallmann syndrome, X-linked recessive
chondrodysplasia punctata, late-onset sensorineural deafness, and microphthalmia and linear skin
defects (MLS) have been linked to the OA1 gene. These contiguous gene syndromes involve the
band Xp22.3 region. Albino phenotypes result when the deleted region includes the OA 1 gene.
Conditions associated with albinism and not because of close linkage
HPS includes oculocutaneous albinism, platelet granule deficiency, and a lysosomal
ceroid storage disorder leading to accumulation of ceroid in tissues throughout the body. It is an
autosomal recessive inherited condition first described in Czechoslovakia by Hermansky and
Pudlak. This syndrome has a high frequency in Puerto Rico. TheHPS gene is localized to band
10q23.1-23.3. Skin pigmentation varies from none to almost normal, with ocular features of
nystagmus, strabismus, foveal hypoplasia, retinal hypopigmentation, and decreased visual acuity.
Late complications of HPS include interstitial pulmonary fibrosis, inflammatory bowel disease, renal
failure, and cardiomyopathy secondary to ceroid deposition.
CHS is an autosomal recessive condition that is characterized by albinism, increased
susceptibility to infections, and deficiency in natural killer cell activity. This rare condition is caused
by mutation to band 1q42.1-q42.2, but the CHS gene product is unknown. The skin, hair, and eye
pigment is reduced in CHS, but the patient usually does not have obvious albinism. Hair color is

light brown to blond. The skin is creamy white to slate gray. Iris pigment is present, and nystagmus
and photophobia may or may not be present.

Physical

Begin with an external examination, checking hair and skin color for depigmentation.
Follow with a complete ocular examination, including a slit-lamp evaluation and dilated fundus
examination. The ocular features common to all types of albinism include the following:
Refractive error and astigmatism
Nystagmus (may compensate with a head tilt that may help improve vision)
Iris depigmentation (usually blue-gray or light brown color) and iris transillumination
Strabismus
Fovea hypoplasia
Reduced depth perception secondary to abnormal neural connections
A positive angle kappa in patients with congenital nystagmus is associated with
albinism. The pathophysiology of the positive angle kappa may relate to the anomalous decussation
of optic axons that characterizes the albinotic visual system. [6]
Once albinism is suspected, the following steps should be taken to ascertain the type of
albinism involved:
Assess the phenotype. If the patient (newborn or adult) completely lacks pigment in
the skin and hair, OCA 1A is the probable diagnosis. The only type of albinism that is associated with
white hair at birth is OCA 1. If a minimal amount of melanin is present, the diagnosis is OCA 1B,
OCA 2, or OCA 3.
CHS should be suspected if the patient has silvery hair and neutrophils with large
inclusions on a blood smear. HPS may be the diagnosis if a minimal-to-moderate hypopigmentation
is present along with decreased blood clotting.
If OCA 1A is suspected, a hair bulb assay may be performed to confirm this diagnosis.
A negative result indicates OCA 1A. However, a positive result could indicate OCA 1B, OCA 2, OCA
3, or OA 1.
A patient with minimal pigment and a positive hair bulb assay could have OCA 1B,
OCA 2, or OCA 3. A patient with only ocular features, presence of hair and skin pigmentation, and a
positive hair bulb assay probably has OA 1.
To distinguish between OCA 1B, OCA 2, or OCA 3, a sequence analysis of the genes
coding for tyrosinase, P protein, and TRP-1 can be completed. Unfortunately, these tests may not be
routinely available. Another alternative test (if available) is a shave skin biopsy (5-8 mm). Cultures of
melanocytes can be assessed for function of tyrosinase, P protein, and TRP-1.
If OA 1 is suspected, a skin biopsy can be taken to check for the presence of
macromelanosomes. It may be necessary to assess the ocular status of female family members.
Since the disorder is X-linked recessive, females would be carriers. They typically have a mudsplattered fundus.
Albinism does not cause a delay in development or mental retardation. Suspect other
causes if this is present.

Causes
Albinism is inherited genetically through specific mutations along the melanin pathway.

Differential Diagnoses

Hermansky-Pudlak Syndrome
Ichthyosis

Laboratory Studies

Hair bulb assays help to indicate the status of tyrosinase activity. Hair bulbs are taken from the
scalp, and the catalytic activity of tyrosinase is determined either by incubation in DOPA and
consequential induction of melanin determined by visual inspection or by a radioactive biochemical
assay in which the samples are incubated with a radiolabeled tyrosine precursor and the amount of
radiolabel released after enzymatic conversion quantified spectrophotometrically. The usefulness of
this test is debatable because a negative result indicates oculocutaneous albinism (OCA) 1A, but a
positive result still leaves the possibility of OCA 1, OCA 2, OCA 3, or OA 1.
The most definitive test in determining the albinism type is genetic sequence analysis. Of
course, the test is useful only for families with individuals who have albinism. The test cannot be used
as a screening tool.

Genetic sequence analysis can be used to determine if a fetus has albinism. Amniocentesis at
16-18 weeks could be performed to obtain a sample for analysis. However, parents should be aware
that children with albinism could function well and have a good prognosis.
Obtain a bleeding time if the patient is planning to undergo surgery. Some physicians believe
that a bleeding time should be obtained in all albino persons. If Hermansky-Pudlak syndrome (HPS) is
suspected, bleeding time, platelet aggregation, and platelet electron microscopy is necessary.
If Chediak-Higashi syndrome (CHS) is suspected, a hematologist should evaluate
polymorphonuclear leukocyte function.

Imaging Studies
Macular optical coherence tomography [7, 8]
Handheld ultra-high-resolution spectral-domain optical coherence tomography (SD-OCT) can be used
in young children with nystagmus and other ocular problems to classify foveal abnormalities and help
determine the cause of the infantile nystagmus with the use of foveal morphology.

Other Tests

Visual-evoked potential tests

Sweep visual-evoked potential (VEP) testing can be used as a predictive tool for
recognition acuity in children with albinism. Predictability was found in a clinical spectrum of albinism.
[9]

Pattern-appearance VEP shows a strong association between the magnitude of the

interhemispheric latency asymmetry and the clinical signs of albinism. [10]
Flash VEP also shows a strong association between the magnitude of the
interhemispheric latency asymmetry and the clinical signs of albinism. [10]

Histologic Findings
Histologic examination of the skin of male patients with this condition and female carriers
of OA1 reveals the presence of macromelanosomes.

Medical Care
Until late 2011, no potential effective treatment or cure existed for albinism, but the following may be
helpful and a new medication may offer some potential hope:

Low-vision aids: No one device can serve the needs of all patients in all situations. Young
children may simply need glasses, while older children may require bifocals. Occasionally, telescopic
lenses mounted on glasses (bioptics) are prescribed for close-up work and distance vision. The use
of Braille is not necessary as children with albinism read the dots visually.
Tinted glasses may be used to reduce photophobia. Some patients do not like tinted lenses;
they may benefit from wearing a cap or visor when outdoors.
For the treatment of strabismus, it is preferred to start eye-patching infants at age 6 months
(prior to completion of eye development). Some cases of strabismus may improve with glasses
correction.
Nitisinone, which is approved by the US Food and Drug Administration (FDA) for treating
hereditary tyrosinemia type 1, elevates plasma tyrosine levels and increases eye and hair
pigmentation. Nitisinone may soon be a potential treatment for people with ocular albinism. [11, 12]

Surgical Care

Albino persons with strabismus rarely achieve binocularity and depth perception after
strabismus surgery, possibly because they lack the necessary neuronal connections.
Patients with albinism tend to do poorly after retinal detachment repair because of nystagmus
and inherently weak retinal pigment epitheliumretinal adhesions.

Consultations

Consult a hematologist if a patient is diagnosed with Chediak-Higashi syndrome (CHS) or

Hermansky-Pudlak syndrome (HPS).
Consultation with a genetic counselor may be helpful.

Medication Summary

No effective medical treatment of albinism is currently available. Nitisinone, which is approved by the
US Food and Drug Administration (FDA) for treating hereditary tyrosinemia type 1, elevates plasma
tyrosine levels and increases eye and hair pigmentation. Nitisinone may soon be a potential treatment
for people with ocular albinism.[11, 12]

Complications

Skin cancer, sunburn

Reduced visual acuity
Social stigma

Prognosis

Patients with albinism have a normal lifespan.

An increased risk of skin cancer exists; however, this is curable.
Patients may have children with no complications. Whether or not their children have albinism
depends on the genetic makeup of their partner.
Albinism does not cause a delay in development or mental retardation.

Patient Education

Remind patients to avoid excess sun exposure.

Provide genetic counseling for the family.