Albinism

Overview

Definition

Albinism is a group of inherited disorders affecting the production of melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis and resulting in hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi.

Classification

Albinism is classified according to its clinical phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics:

• Oculocutaneous albinism ( OCA OCA Primary Biliary Cholangitis): affects the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, eyes, and hair (most common type)
• Ocular albinism ( OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis): only affects the eyes

Epidemiology

• Affects 1 in 17,000 people in the United States (approximately 18,000 people)
• Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria:
  • Both males and females can have OCA OCA Primary Biliary Cholangitis.
  • OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis only affects males.
• Affects all races

Etiology

Albinism results from inherited genetic mutations Genetic Mutations Carcinogenesis.

• OCA OCA Primary Biliary Cholangitis: 
  • 8 subtypes
  • Results from mutations in genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure responsible for different components of the melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis synthesis Synthesis Polymerase Chain Reaction (PCR) pathway
  • Autosomal recessive inheritance Autosomal recessive inheritance Autosomal Recessive and Autosomal Dominant Inheritance pattern
• OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis: 
  • 2 subtypes
  • Caused by gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations with X-linked inheritance X-linked inheritance Genetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases. Alport Syndrome pattern

Pathophysiology and Clinical Presentation

Pathophysiology

• Impaired melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis biosynthesis Biosynthesis The biosynthesis of peptides and proteins on ribosomes, directed by messenger RNA, via transfer RNA that is charged with standard proteinogenic amino acids. Virology in melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions → absence or ↓ melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis → hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, hair, and eyes
• Depending on the OCA OCA Primary Biliary Cholangitis type, there may be complete absence of pigmentation or a variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables amount of melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis production.
• The number of melanocytes Melanocytes Mammalian pigment cells that produce melanins, pigments found mainly in the epidermis, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called melanosomes. The large non-mammalian melanin-containing cells are called melanophores. Skin: Structure and Functions is not reduced.
• Melanin Melanin Insoluble polymers of tyrosine derivatives found in and causing darkness in skin (skin pigmentation), hair, and feathers providing protection against sunburn induced by sunlight. Carotenes contribute yellow and red coloration. Seborrheic Keratosis is also important for the development of structures of the eye and the routing of nerve fibers Nerve Fibers Slender processes of neurons, including the axons and their glial envelopes (myelin sheath). Nerve fibers conduct nerve impulses to and from the central nervous system. Nervous System: Histology from the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy to the optic chiasm Optic Chiasm The x-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. The Visual Pathway and Related Disorders → ↓ vision Vision Ophthalmic Exam in albinism

Clinical presentation

The presentation can vary depending on the different genetic subtypes. However, the following are general signs and symptoms:

• OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis:
  • ↓ Pigmentation of the iris and retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
  • Visual defects present at birth:
    • ↓ Visual acuity Visual Acuity Clarity or sharpness of ocular vision or the ability of the eye to see fine details. Visual acuity depends on the functions of retina, neuronal transmission, and the interpretative ability of the brain. Normal visual acuity is expressed as 20/20 indicating that one can see at 20 feet what should normally be seen at that distance. Visual acuity can also be influenced by brightness, color, and contrast. Ophthalmic Exam due to foveal hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS)
    • Photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache
    • ↓ Depth perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment
    • Lack of normal binocular vision Vision Ophthalmic Exam
  • Nystagmus (involuntary movements of the eyes)
  • Strabismus Strabismus Strabismus is the misalignment of the eyes while fixating the gaze on an object. Strabismus can be idiopathic, but it may also be caused by cerebral palsy, uncorrected refractive errors, and extraocular muscle or cranial nerve dysfunction. Strabismus (eyes do not align properly)
• OCA OCA Primary Biliary Cholangitis:
  • Ocular issues, as above
  • Hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and hair:
    • The degree of hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi varies.
    • Can range from white to blond/reddish-blonde hair, eyebrows, and eyelashes
  • Photosensitivity Photosensitivity Tetracyclines:
    • Sunburns
    • Some subtypes develop pigmented nevi Pigmented nevi A collective term for the various types of nevi and melanomas. Female Genitourinary Examination and lentigines.

Diagnosis and Management

Diagnosis

• Albinism is a clinical diagnosis.
• Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies is available but is not routinely performed.

Management

There is no currently available cure, and management is mainly supportive.

• Strict protection from the sun:
  • Sunscreen Sunscreen Chemical or physical agents that protect the skin from sunburn and erythema by absorbing or blocking ultraviolet radiation. Melanoma
  • Protective clothing
  • Sunglasses
• Regular Regular Insulin skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions examination every 6–12 months for early diagnosis and treatment of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions cancer
• Ocular manifestations:
  • Frequent ophthalmologic examinations
  • Treatment of refractive errors Refractive errors By refraction, the light that enters the eye is focused onto a particular point of the retina. The main refractive components of the eye are the cornea and the lens. When the corneal curvature, the refractive power of the lens, does not match the size of the eye, ametropia or a refractive error occurs. Refractive Errors with glasses or contacts
  • Surgery to correct strabismus Strabismus Strabismus is the misalignment of the eyes while fixating the gaze on an object. Strabismus can be idiopathic, but it may also be caused by cerebral palsy, uncorrected refractive errors, and extraocular muscle or cranial nerve dysfunction. Strabismus or cataracts, if needed
• Genetic counseling Genetic Counseling An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered. Myotonic Dystrophies

Complications

Albinism is associated with an increased risk of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions cancer, with squamous cell carcinoma Squamous cell carcinoma Cutaneous squamous cell carcinoma (cSCC) is caused by malignant proliferation of atypical keratinocytes. This condition is the 2nd most common skin malignancy and usually affects sun-exposed areas of fair-skinned patients. The cancer presents as a firm, erythematous, keratotic plaque or papule. Squamous Cell Carcinoma (SCC) being the most common.

Differential Diagnosis

The following conditions are differential for OA OA Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis:

• Optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS): a congenital Congenital Chorioretinitis condition characterized by underdevelopment of the optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions resulting in vision Vision Ophthalmic Exam loss in children. Nystagmus is also seen in this condition. Other central nervous system Central nervous system The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Nervous System: Anatomy, Structure, and Classification abnormalities often co-exist. Diagnosis made clinically with fundoscopic examination. However, imaging is often obtained to evaluate for other possible defects. Management is aimed at reducing the impact of vision Vision Ophthalmic Exam loss on development.
• Inherited retinal dystrophy: encompasses a group of genetic retinal disorders with variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables inheritance patterns. Degeneration and loss of the photoreceptors, rods, and cones occurs, which leads to vision Vision Ophthalmic Exam loss, night blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity, photosensitivity Photosensitivity Tetracyclines, and, possibly, color blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity. The diagnosis is made clinically and confirmed with electro-diagnostic testing. There is no cure currently available, and management is challenging and limited.
• Aniridia Aniridia A congenital abnormality in which there is only a rudimentary iris. This is due to the failure of the optic cup to grow. Aniridia also occurs in a hereditary form, usually autosomal dominant. Wilms Tumor: a rare congenital Congenital Chorioretinitis ocular disorder that causes abnormal development of the iris. The cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy, lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy, fovea Fovea An area approximately 1. 5 millimeters in diameter within the macula lutea where the retina thins out greatly because of the oblique shifting of all layers except the pigment epithelium layer. It includes the sloping walls of the fovea (clivus) and contains a few rods in its periphery. In its center (foveola) are the cones most adapted to yield high visual acuity, each cone being connected to only one ganglion cell. Eye: Anatomy, and optic nerve Optic nerve The 2nd cranial nerve which conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. The 12 Cranial Nerves: Overview and Functions may also be affected. Affected individuals have low visual acuity Visual Acuity Clarity or sharpness of ocular vision or the ability of the eye to see fine details. Visual acuity depends on the functions of retina, neuronal transmission, and the interpretative ability of the brain. Normal visual acuity is expressed as 20/20 indicating that one can see at 20 feet what should normally be seen at that distance. Visual acuity can also be influenced by brightness, color, and contrast. Ophthalmic Exam, photosensitivity Photosensitivity Tetracyclines, and nystagmus. Most notably, the iris of the eye is partially or completely absent. The condition is diagnosed with an ophthalmologic examination. Management includes vision Vision Ophthalmic Exam correction, lubricating drops, and treatment of associated conditions (e.g., cataracts, glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma).

The following conditions must be considered in the differential diagnosis for OCA OCA Primary Biliary Cholangitis:

• Prader-Willi syndrome Prader-Willi syndrome Prader-Willi syndrome (PWS) is a rare autosomal neurodevelopmental genetic disorders mapped to a specific region of chromosome 15 attributed to genomic imprinting. A paternally derived chromosome 15 with this deletion results in 15q11-13 paternal deletion syndrome, or PWS. Prader-Willi Syndrome and Angelman Syndrome and Angelman syndrome Angelman syndrome Angelman syndrome (AS) is a rare autosomal neurodevelopmental genetic disorders mapped to a specific region of chromosome 15 attributed to genomic imprinting. A maternally derived chromosome 15 with this deletion results in 15q11-13 maternal deletion syndrome, or AS. Prader-Willi Syndrome and Angelman Syndrome: rare neurodevelopmental disorders caused by microdeletions on chromosome 15 Chromosome 15 Marfan Syndrome, which can include the gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics for OCA OCA Primary Biliary Cholangitis in approximately 1% of cases. Affected children present with the clinical characteristics of OCA OCA Primary Biliary Cholangitis in addition to the physical, behavioral, and developmental abnormalities seen in Prader-Willi or Angelman syndromes (e.g., hypotonia Hypotonia Duchenne Muscular Dystrophy, feeding issues, and developmental delay). Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies confirms the diagnosis. Management requires a multidisciplinary team of medical and therapy specialists.
• Hermansky-Pudlak syndrome: a rare autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance condition characterized by OCA-like findings and platelet abnormalities that result in bleeding problems and easy bruising Easy bruising Chédiak-Higashi Syndrome. Affected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have light skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, hair, and eyes. Laboratory studies and genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies confirm the diagnosis. In addition to measures used in OCA OCA Primary Biliary Cholangitis, management also involves platelet transfusions and desmopressin Desmopressin Hemophilia for bleeding.
• Chediak-Higashi syndrome: a rare autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance condition characterized by impaired lysis of phagocytized bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology. The syndrome presents with recurrent bacterial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, OCA-like findings, neurologic dysfunction, and coagulation defects. Affected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship often have fair skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and grey, silvery hair. The diagnosis is made by evaluating the peripheral blood smear Peripheral Blood Smear Anemia: Overview and Types for giant granules in neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation and genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Management involves stem cell transplantation, interferon gamma, and antibiotic therapy to prevent infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.