Oculocutaneous albinism type I or type 1A is an

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

skin disease A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sy ...

. This subtype of

oculocutaneous albinism Oculocutaneous albinism is a form of albinism involving the eyes ('' oculo-''), the skin (''-cutaneous''), and the hair. Overall, an estimated 1 in 20,000 people worldwide are born with oculocutaneous albinism. OCA is caused by mutations in seve ...

is caused when the gene for

tyrosinase Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxylat ...

(symbol TYR or OCA1) does not function properly. The

location In geography, location or place are used to denote a region (point, line, or area) on Earth's surface or elsewhere. The term ''location'' generally implies a higher degree of certainty than ''place'', the latter often indicating an entity with an ...

of OCA1 may be written as "11q1.4-q2.1", meaning it is on

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

11, long arm, somewhere in the range of band 1, sub-band 4, and band 2, sub-band 1. Since the disorder is autosomal recessive,

genetic counseling Genetic counseling is the process of investigating individuals and families affected by or at risk of genetic disorders to help them understand and adapt to the medical, psychological and familial implications of genetic contributions to disease; t ...

can be used to determine if both parents are heterozygous for the condition when considering having children. If both parents are heterozygous, their child has a 25% chance of inheriting both recessive copies of OCA1 and having the skin disease. This symptoms in this disease include absence of pigmentation, due to a mutation that affects melanin levels in the eyes, hair, and skin. This rare disease is found in 1 out of 20,000 people around the world, being much more prevalent in Caucasians. There is no known cure for this disease as of present, but there are various ways to manage this disease, including safety around the sun and regular checks for other skin diseases such as skin cancer.

Signs and symptoms

OCA is characterized by the absence of pigmentation caused by the mutation that effects the production of tyrosinase that causes partial or total absence of melanin in the hair, skin, and eyes. Reduction in melanin production specifically in the peripheral retina during embryonic development can trigger other symptoms such as abnormal nerve fiber projection that causes defects in neuronal migration that interrupts visual pathways and creates reduced visual acuity in the range of 20/60 to 20/400. This vision acuity is dependent upon the amount of pigmentation in the eye. Acuity is usually better in individuals with greater amounts of pigment. Aside from decreased pigment in the iris and retina, optic changes include decreased visual acuity, misrouting of the optic nerves at the chiasm, and

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

. OCA1 is one of the more extreme types of albinism where the iris is translucent and the eye appears pink or red in ambient light and have white skin with slight to no pigmentation when other types may have residual pigmentation. OCA1 is caused by mutations in the TYR gene, where there is a complete lack of tyrosinase activity.

Genetics

The tyrosinase (TYR) gene is located on chromosome 11q14. This protein coding gene produces

, an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

which catalyzes a total of three steps in the conversion of

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

to the end product,

melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

. This enzyme and conversion process takes place within

melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...

s, which are specialized cells for melanin production. Melanin is a large group of molecules that give skin, eyes, and hair their respective colors. It is also partially responsible for vision, as it protects the light sensitive portion of the eye, the

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...

, through absorbing light. OCA Type 1A is an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

condition, meaning there is a

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

compound heterozygous In medical genetics, compound heterozygosity is the condition of having two or more heterogeneous recessive alleles at a particular locus that can cause genetic disorders, genetic disease in a heterozygous state; that is, an organism is a compound h ...

mutation related to the TYR gene. There are many different types of albinism, differing due to the effects of various mutations. Oculocutaneous albinism type IA is the most severe type of albinism, as it is characterized by no melanin production. Other types of albinism have limited melanin production. Because type IA Albinism has no functioning copies of the gene, it is the most severe type of albinism. The mutations on this gene lead to a complete lack of tyrosinase activity as the inactive enzyme is produced. An inactive enzyme can be caused by a

missense In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense mu ...

nonsense Nonsense is a communication, via speech, writing, or any other symbolic system, that lacks any coherent meaning. Sometimes in ordinary usage, nonsense is synonymous with absurdity or the ridiculous To be ridiculous is to be something which is ...

mutation. Due to the lack of enzymes needed to catalyze the production of melanin, patients do not have melanin protecting them from the sun, resulting in sensitive eyes, skin, and other symptoms mentioned in the signs and symptoms of OCA1A. The different forms of albinism and range of severity is dependent upon the level of melanin production, which depends on the level of tyrosinase activity.

Diagnosis

Because albinism is autosomal recessive, prenatal genetic screening and genetic counseling can be performed to diagnose OCA early on. When pathogenic variants are known to be present in an affected family, carrier testing can also be conducted. The level of expression can be variable depending on the pigmentation background, so phenotypically, OCA can be expressed on a spectrum. OCA is heterogenous, with OCA1 being caused by a mutation in the ''TYR'' gene. The separate subdivisions are categorized by the genes that they effect. The seven types are not evenly distributed amongst ethnic groups with OCA1 being the subtype most prominent in Caucasians - "accounting for approximately 50% of cases worldwide." Previously, diagnosis was done from observation of hypopigmentation which is obvious at birth, but this is now insufficient early on to distinguish between the seven major types of OCA. Prenatal testing has been achieved through fetal skin biopsy followed by subsequent histologic and electron microscope examination for melanin levels. Clinical findings have established that molecular genetic testing of ''TYR'', the gene encoding tyrosinase, can distinguish between 1A and 1B because the phenotypes can be identical during the first year of life. OCA1A results in complete loss of tyrosinase enzyme activity. Individuals with 1B will experience increased pigmentation with age because they have a very low level of melanin production that can increase. The histological approach for prenatal diagnosis is useful for all families at risk for OCA1 whereas the molecular genetic test is only helpful when at least one mutation is known.

Management

There is currently no treatment for this disease. The extremely hypopigmented skin that is characteristic in OCA1 particularly leads to risk of skin damage and non-melanotic skin cancers due to increased sensitivity to UV rays. In OCA1B, because there is some presence of melanin, it grows with age and pigmentation can increase; the same cannot be said for OCA1A. Individuals affected by OCA1A should be attentive to the amount of sun exposure they experience and wear proper protection such as clothing that covers the skin. Additionally, individuals may need corrective visual aids for their visual acuity of 1/10 or less with intense photophobia. Visual aids can both improve vision or protect eyes from bright lights. These visual aids can be adjusted for based on individual needs. Individuals should receive annual skin evaluation to access for damage or skin cancers that can be induced from sun exposure. In some situations, therapy or surgery can correct crossed eyes (

strabismus Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a ...

) or rapid eye movements (

Epidemiology

The highest frequency of Albinism type IA is in Northern Ireland, with a phenotype frequency of around 1: 10,000. First cousin - marriages accounted for 4.5% of the parents of patients. Additionally, symptoms that could be heterozygous mutations, such as abnormal iris translucency occurred in 70% of the parents and children of individuals affected with this condition. In general, the phenotypical appearance of OCA1A is associated with northern and western Europe. This is because over 50% of OCA1 subjects are Caucasians. OCA1 is also the most common form of Albinism in China and Japan. The overall frequency is 1: 20,000 people in the world.

References

External links

{{Medical resources , DiseasesDB = , ICD10 = E70.3 , ICD9 = , ICDO = , OMIM = 203100 , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = , Orphanet = 352731 Autosomal recessive disorders