Albinism Race: All races appear to be equally affected by the associated mutations. However, OCA type 2 is reportedly more common among Africans and African Americans (1 case per 10,000 population) than in whites (1 case per 36,000 population). In addition, OCA type 3 has only been genetically confirmed in African and African American individuals. Sex: The incidence of these albino diseases is equal for men and women. Age: All of these diseases present in neonates. CHS consists of an accelerated phase that occurs years to decades after birth. History: The characteristic hypopigmentation of albinism is apparent at birth. An increase in the pigmentation of the skin and/or the hair may occur with age, especially in individuals who are mildly affected. In CHS, respiratory infections can occur within a few days of birth. Recurrent infections and bleeding diathesis increase with the age of the patient with CHS. The accelerated phase of CHS generally manifests by the first decade of life. In HPS, the bleeding diathesis can occur within a few days of birth generally during circumcision. Throughout life, patients with HPS experience mild-to-moderate bleeding events, including bruising, epistaxis, gingival bleeding, prolonged bleeding during menstruation or after tooth extraction, postpartum hemorrhage, and bleeding colitis. The respiratory system is the primary organ system affected by the ceroid storage disease. Restrictive lung disease usually progresses slowly for the first few decades of life and then advances rapidly. The occurrence and the extent of other organ system dysfunctions are variable. In GS, the immunodeficiency or neurological defects can occur shortly after birth. Physical: OCA type 1 primarily manifests with complete absence of pigment in the skin, the hair, and the eyes, and this category is termed OCA type 1A. However, some patients can present with moderate pigmentation in these tissues (termed OCA type 1B) or pigment in hair follicles of the cooler areas of the body, such as the arms and the legs (termed OCA type 1TS, ie, temperature sensitive). All forms of OCA type 1 also present with photophobia, moderate-to-severe reduced visual acuity, and nystagmus. The latter two ocular dysfunctions result from a misrouting of the optic fibers from the retina to the visual cortex of the brain. OCA type 2 does not present with complete absence of pigment but rather manifests with a minimal-to-moderate amount of pigment remaining in the skin, the hair, and the eyes. Many patients with OCA type 2 can develop pigmented freckles, lentigines, and/or nevi with age. The ocular presentations are similar to those in OCA type 1. OCA type 3 manifests with minimal pigment reduction in the skin, the hair, and the eyes. This form of albinism was previously referred to as Rufous albinism and possibly Brown albinism. To date, OCA type 3 has only been genetically confirmed in dark-skinned individuals (of African heritage). The reduction of cutaneous and ocular pigmentation may only be apparent in comparison with the complexion coloration of family members. The ocular presentations are similar to those in OCA type 1, but they are not as severe. OCA type 4 manifests with a phenotype resembling OCA type 2. OA manifests with ocular depigmentation and iris translucency. In addition, patients with OA present with congenital motor nystagmus that may be accompanied by reduced visual acuity, refractive errors, fundus hypopigmentation, lack of foveal reflex, and strabismus. Cutaneous depigmentation is not apparent. CHS manifests with moderate-to-complete absence of pigment in the skin, the hair, and the eyes. The hypopigmentation of the hair in CHS generally has a distinct silvery, metallic sheen. Respiratory tract infections frequently occur shortly after birth. HPS manifests with a variable amount of depigmentation in the skin, the hair, and the eyes. Ophthalmic findings vary. GS manifests with a mild form of albinism (ie, pale skin). Distinctive in GS is the presentation of silvery gray hair at birth. Causes: The causes of these diseases are mutations in specific genes. OCA type 1 results from mutations in the tyrosinase gene, which maps to band 11q14-2 and is inherited as an autosomal recessive trait. The tyrosinase gene encodes an enzyme that initiates the synthesis of melanin using the substrate tyrosine. Specifically, tyrosinase hydroxylates tyrosine to dihydroxyphenylalanine (DOPA) and subsequently dehydroxylates DOPA to DOPA-oxidase. More than 70 mutations have been identified in tyrosinase that result in the dysfunction or lack of synthesis of this enzyme. Most patients with OCA type 1 have compound heterozygosity for mutations in the tyrosinase gene. OCA type 2 results from mutation in the P gene, which maps to band 15q11-13 and is inherited as an autosomal recessive trait. The P gene encodes a 110-kd protein with 12 putative transmembrane domains localized to the limiting membrane of the pigment granule (ie, melanosome). The function of the P protein in melanin synthesis has yet to be determined. OCA type 3 results from mutation in the tyrosinase-related protein-1 (Tyrp1) gene, which maps to band 9p23 and is inherited as an autosomal recessive trait. The Tyrp1 gene encodes a protein that has been shown to have a dihydroxyindole carboxylic acid (DHICA) oxidase activity in the murine system. DHICA oxidase is a catalytic step downstream from tyrosinase in the biosynthesis of melanin from tyrosine. The function of Tyrp1 in human melanogenesis has yet to be confirmed. OCA type 4 results from mutations in the membrane-associated transporter protein (MATP) gene, which maps to band 5p13.3 and is inherited as an autosomal recessive trait. The MATP gene encodes a 58-kd protein with 12 predicted transmembrane domains. The function of MATP in melanogenesis is presently unknown. OA results from mutation in a gene on the X chromosome, which maps to band Xp22.3-22.2 and is inherited as an X-linked recessive trait. The function of the OA gene product is unknown. CHS results from mutation in the LYST gene, which maps to band 1q42-43 and is inherited as an autosomal recessive trait. The LYST gene encodes a large 429-kd protein that putatively functions in the translocation of material from the Golgi apparatus to target sites in affected cells. As a result, the synthesis of melanosomes by the melanocyte, of delta granules by the platelet, and of lysosomes by some of the leukocytes (ie, neutrophils and natural killer lymphocytes) is impaired. HPS is inherited as an autosomal recessive trait and exists with loci heterogeneity. The initial form of HPS identified, termed HPS type 1 (HPS1), results from a gene that maps to band 10q23.1-23.3. The HPS gene encodes a 79-kd protein of unknown function. HPS type 2 (HPS2) results from mutations in a gene that encodes the beta subunit of the adaptin 3 complex (AP3). AP3 is involved in trafficking specific glycoproteins from the Golgi apparatus to target sites in affected cells. Many patients with HPS have normal HPS1 and HPS2 genes/gene products, suggesting that additional genetic causes for other subsets of HPS exist. To date, 7 genetically distinct forms of HPS have been identified in the human population (see related e-medicine chapter). GS is inherited as an autosomal recessive trait. Two primary genetic variants are known. One results from mutations in the RAB27A gene located at band 15q21 that encodes the GTP-binding protein Rab27a. The other results from mutations in the MYO5A gene located at band 15q21 that encodes the unconventional myosin motor protein myosin5a. In the melanocyte, these 2 gene products, along with a third bridging protein (ie, melanophilin) form a complex that facilitates the translocation of melanosomes along the dendrites of the melanocyte and their subsequent capture at the dendritic tips. Medical Care: No treatment is available for hypopigmentation in the skin, the hair, or the eyes. The use of broad-spectrum sunscreens and clothing is recommended to prevent ultraviolet-induced damage to the skin. Visual impairment can be improved by using corrective lenses. Most therapy for CHS and GS is symptomatic in nature. Appropriate antibiotics should be administered to treat infections. Bone marrow transplantation can correct and improve hematologic and immunologic defects in persons with CHS and GS, respectively. No therapy is effective for the nonpigmentary disorders of HPS. If the bleeding diathesis is extreme, platelet and blood transfusions may be considered. If the granulomatous colitis or the pulmonary fibrosis becomes extreme, high-dose steroids may be considered. Further Outpatient Care: Patients with OCA should be frequently screened for skin cancer. Patients with CHS, HPS, and GS should be routinely monitored for advancement of the nonpigmentary disorders. Complications: Complications of OCA type 1 include photophobia, severe-to-moderate reduced visual acuity, and nystagmus. The ocular complications in OCA type 2, OCA type 3, and OCA type 4 are similar to those in OCA type 1, but, in OCA type 3, they are not as severe. Complications of CHS include easy bruising, mucosal bleeding, epistaxis and petechiae, recurrent infections primarily involving the respiratory system, and neutropenia. In the accelerated phase, fever; anemia; neutropenia; and, occasionally, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and jaundice may occur. Neurologic problems in CHS may include a peripheral and cranial neuropathy, autonomic dysfunction, weakness and sensory deficits, loss of deep tendon reflexes, clumsiness with a wide-based gait, seizures, and decreased motor nerve conduction velocities. Long-term complications of HPS include pulmonary fibrosis, granulomatous colitis, gingivitis, and kidney failure. Patient Education: Patients should use broad-spectrum sunscreens and should wear appropriate clothing to prevent ultraviolet-induced damage to the skin. Visual impairment can be improved by using corrective lenses. Source: http://www.emedicine.com/DERM/topic12.htm