Related Terms

• Albinism, albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells, autosomal recessive inheritance, bleeding tendency diathesis, cardiomyopathy, colitis, delta storage pool disease, HPS, HPS1, HPS2, HPS3, HPS4, HPS5, HPS6, HPS7, HPS type 1, HPS type 2, HPS type 3, HPS type 4, HPS type 5, HPS type 6, HPS type 7, HPS type 8, pulmonary fibrosis, Ty-pos OCA, tyrosinase-positive oculocutaneous albinism.

Background

• Hermansky-Pudlak syndrome (HPS) belongs to a group of disorders known as albinism. Albinism is characterized by decreased or absent pigment (coloring) in the skin, hair, and iris of the eyes. In some cases, albinism includes other eye problems, such as decreased visual clearness, sensitivity to light, involuntary eye movements, problems with the iris, and decreased pigment in the retina on the back of the eye.

• Albinism is caused by mutations or defects in genes that provide instructions for making the pigment melanin, a material that changes the color of light it reflects and provides color to hair, skin, and eyes. Unlike some types of albinism, in which melanin is completely absent, people with HPS do produce some melanin, so this may be a less severe type of the disease. HPS includes a bleeding tendency and a predisposition to lung disease. HPS may also include inflammatory bowel disease or kidney disease.

• There are eight types of HPS, each of which is caused by a different genetic mutation or defect. HPS is inherited, or passed down among family members, as an autosomal recessive trait. Individuals receive two copies of most genes, one from the mother and one from the father. To inherit an autosomal recessive trait, an individual must inherit two defective copies of the causative gene. Individuals who inherit only one copy of the defective gene are called carriers. Carriers generally do not have any symptoms but may pass on the disorder to their children.

• Genes that may lead to HPS in humans include the HPS1,HPS2 (AP3B1), HPS3, HPS4, HPS5, HPS6, and HPS7 genes, which are involved in vesicle formation within cells. Vesicles transport substances within the cell that allow for normal functioning.

• Symptoms of HPS vary widely among patients and may include bleeding problems, such as easy bruising, nosebleeds, and extended bleeding times. Improper handling of ceroid, a naturally occurring fatty substance, can result in pulmonary fibrosis, inflammatory bowel disease, kidney disease, and eye problems resulting from a lack of pigmentation in the eye, leading to light sensitivity, crossed eyes, and involuntary eye movements.

• Overall prevalence of HPS is about one in 500,000-1,000,000 in the general population. The prevalence of HPS in Puerto Rico, however, is estimated at about one in 1,800-2,000. HPS type 1 is the most common single-gene disorder in Puerto Rico. Single-gene disorders are very rare genetic diseases. HPS type 3 is more common in inland Puerto Rico than in coastal areas. The prevalence of all types of carriers in Puerto Rico is about one in 21. This disease is most common in Puerto Rico, but it has been reported in Switzerland, Japan, and other countries. Cases of Ashkenazi Jews with mild symptoms and mutations in the HPS3 gene have been reported. HPS appears to affect males and females in equal numbers.

• About 70% of people with HPS die from complications of the disorder, including lung problems, excessive bleeding, or problems with the intestine, liver, or kidneys. Life expectancy is typically about 40-50 years.

Risk Factors

• Family history: Hermansky-Pudlak syndrome (HPS) is inherited, or passed down among family members. Therefore, the only known risk factor is a family history of the disorder.

• Autosomal recessive inheritance: HPS follows an autosomal recessive pattern of inheritance, meaning that a person must inherit two copies of the defective gene, one from each parent. Individuals who inherit only one copy of the defective HPS gene generally have no symptoms and are called carriers because they can pass on the disorder to their children.

• If one parent is a carrier, or has only one copy of the defective gene, then each child has a 50% chance of inheriting one defective gene and also being a carrier. If both parents are carriers, each child has a 25% chance of inheriting two defective genes, a 50% chance of inheriting only one defective gene, and a 25% chance of inheriting neither defective gene. Therefore, if both parents are carriers, about one out of four children will have the disorder.

• Prevalence: Overall prevalence of HPS is about one in 500,000-1,000,000 in the general population. The prevalence of HPS in Puerto Rico, however, is estimated at about one in 1,800-one in 2,000. HPS type 1 is the most common single-gene disorder in Puerto Rico. Single-gene disorders are very rare genetic diseases. HPS type 3, on the other hand, is more common in inland Puerto Rico than in coastal areas. The prevalence of all types of HPS carriers in Puerto Rico is about one in 21.

• HPS has been found in higher-than-normal numbers among people in a village in the Swiss Alps, people of Dutch and Ashkenazi Jewish heritage, and individuals from Turkey, Mexico, Pakistan, and Japan. HPS appears to affect males and females in equal numbers.

Causes

• Genetic mutations: There are eight types of Hermansky-Pudlak syndrome (HPS), each of which is caused by a different genetic mutation or defect. HPS type 1 is caused by mutations in the HPS1 gene; HPS type 2 by mutations in the AP3B1 gene (also known as HPS2); HPS type 3 by mutations in the HPS3 gene; HPS type 4 by mutations in the HPS4 gene; HPS type 5 by mutations in the HPS5 gene; HPS type 6 by mutations in the HPS6 gene; HPS type 7 by mutations in the DTNBP1 gene; and HPS type 8 by mutations in the BLOC1S3 gene. All of these genes are involved in vesicle formation in cells. Vesicles transport substances within the cell that allow for normal functioning.

• The genes that cause the various types of HPS provide instructions for making proteins essential to the normal production of the pigment melanin, a material that changes the color of light it reflects and provides color to hair, skin, and iris of the eyes. Melanin also absorbs ultraviolet light from the sun to protect the skin. Because melanin is absent or decreased in HPS, people with albinism are at increased risk of skin damage caused by the sun. Unlike some types of albinism in which melanin is absent, people with HPS do produce some melanin, so this may be a less severe form of the disease. HPS includes a bleeding tendency and an increased predisposition to lung disease. HPS may also include inflammatory bowel disease or kidney disease.

• Autosomal recessive inheritance: HPS is inherited, or passed down among family members, as an autosomal recessive trait. Individuals receive two copies of most genes, one from the mother and one from the father. To inherit an autosomal recessive trait, an individual must inherit two defective copies of the causative gene.

• Individuals who inherit only one copy of the defective gene generally have no symptoms and are called carriers, because they can pass on the disorder to their children. If one parent is a carrier, or has only one copy of the defective gene, then each child has a 50% chance of inheriting one defective gene and also being a carrier. If both parents are carriers, each child has a 25% chance of inheriting two defective genes, a 50% chance of inheriting only one defective gene, and a 25% chance of inheriting neither defective gene. Therefore, if both parents are carriers, about one out of four children will have the disorder.

• There is a lack of evidence to suggest that HPS can occur as a result of a spontaneous mutation.

Signs and Symptoms

• General: Hermansky-Pudlak syndrome (HPS) belongs to a group of disorders related to albinism. Symptoms of HPS vary widely among patients and may include bleeding problems, such as easy bruising, nosebleeds, and extended bleeding times. Improper handling of ceroid, a naturally occurring fatty substance, can result in pulmonary fibrosis, inflammatory bowel disease, kidney disease, and eye problems resulting from a lack of pigmentation in the eye, leading to light sensitivity, crossed eyes, and involuntary eye movements.

• Bleeding: People with HPS are prone to abnormal and excessive bleeding episodes caused by platelet dysfunction, which can lead to decreased clotting ability for wound healing (called thrombocytopenia). A mutation in one of the genes related to HPS may be responsible for this symptom. People with HPS may experience frequent bruising, nosebleeds, bleeding gums, gastrointestinal bleeding, or prolonged bleeding during menstruation, after dental or other surgery, or during childbirth. Many individuals are diagnosed with HPS when abnormal bleeding occurs after circumcision.

• Eyes: Individuals with HPS have a number of symptoms related to the eyes. Nystagmus (involuntary eye movements) may be noticeable at birth. These movements may be very fast early in life and slow down with age. Nystagmus can be worsened by stress and fatigue. Other eye symptoms may include sensitivity to light, wandering eye movements, decreased visual attention, decreased visual clearness, problems with the optic nerve or retina, crossed eyes, color blindness, cataracts (clouding of the lens of the eye), and abnormalities of the iris. Most people with HPS are legally blind because of the progression of cataracts, retinal degeneration, or both. A genetic mutation in one of the genes related to HPS may be responsible for these symptoms.

• Gastrointestinal: Ceroid, a fatty substance, may collect in the intestines and cause symptoms of diarrhea, cramps, and bloody stools similar to those seen in inflammatory bowel disease. People with HPS may develop inflammation and bleeding in the colon, also known as colitis, between 12 and 30 years of age. This condition tends to be severe in about 15% of people with HPS, some of whom require surgical removal of part of the intestine. While the colon is most often affected, inflammation and bleeding can occur in any part of the digestive tract, from the oral cavity to the anus. Symptoms of colitis may include abdominal pain, diarrhea, gastrointestinal bleeding, weight loss, and cramps.

• Hair: Hair color may range from white to brown and may darken with age from alterations in the body's production of the pigment melanin, a material that changes the color of light it reflects and provides color to hair, skin, and iris of the eyes.

• Heart: Ceroid, a fatty substance, may accumulate in the heart and cause cardiomyopathy, a disease that involves inflammation of the heart muscle, causing it to not work properly. Symptoms include buildup of fluid in the lungs or legs, fatigue, weakness, and shortness of breath.

• Kidney: The accumulation of ceroid, a fatty substance, can cause progressive damage to the kidneys. This may result in scarring of the kidney tissue, which eventually prevents the kidneys from functioning normally and can lead to kidney failure.

• Lungs: Ceroid, a fatty substance, may accumulate in the lungs and cause pulmonary fibrosis, a disease that involves scarring of the lungs and may result in shortness of breath, a dry, hacking cough, fatigue, weakness, and rapid weight loss.

• Skin: People with HPS may have skin color that ranges from white to olive and is generally noticeably lighter than that observed in unaffected family members. This difference is caused by alterations in the body's production of the pigment melanin, a material that changes the color of light it reflects and provides color to hair, skin, and iris of the eyes. Freckles are common in individuals with HPS. Repeated exposure to the sun over the course of several years may cause skin to become rough and thick (called pachydermia) and may cause the development of precancerous and cancerous lesions. Melanin also absorbs ultraviolet light from the sun to protect the skin. Because melanin is absent or decreased, people with HPS are at increased risk of skin damage caused by the sun, including skin cancers such as basal cell and squamous cell carcinomas. Melanoma, another skin cancer, tends to be rare with HPS. People of Puerto Rican heritage may be more severely affected.

Types of the Disease

• General: There are eight types of Hermansky-Pudlak syndrome (HPS), each of which is caused by a different genetic mutation or defect. Information on the differences between these types of HPS is currently lacking.

• HPS type 1: HPS type 1 is caused by mutations in the HPS1 gene, which provides instructions for making the HPS 1 protein (HPS1). This protein is likely involved in the normal function and development of the organelles (tiny organs) found in cells. HPS type 1 has been found among people of Puerto Rican, Swiss, Japanese, and Irish heritage.

• HPS type 2: HPS type 2 is caused by mutations in the AP3B1 (or HPS2) gene, which provides instructions for making the AP-3 complex subunit beta-1 protein. The exact function of this protein is currently unknown. HPS type 2 has been associated with immune system problems.

• HPS type 3: HPS type 3 is caused by mutations in the HPS3 gene, which provides instructions for making the HPS 3 protein (HPS3), whose function is currently unknown. Hair and skin color may be darker in individuals with this type of HPS.

• HPS type 4: HPS type 4 is caused by mutations in the HPS4 gene, which provides instructions for making the HPS 4 protein (HPS4), whose exact function is currently unknown.

• HPS type 5: HPS type 5 is caused by mutations in the HPS5 gene, which provides instructions for making the HPS 5 protein (HPS5), whose exact function is currently unknown.

• HPS type 6: HPS type 6 is caused by mutations in the HPS6 gene, which provides instructions for making the HPS 6 protein (HPS6), whose exact function is currently unknown.

• HPS type 7: HPS type 7 is caused by mutations in the DTNBP1 gene, which provides instructions for making the dysbindin protein. This protein may be involved in the development of organelles called lysosomes, which contain digestive enzymes and serve as a cleanup function within the cell by digesting organelles that are no longer functioning properly, or viruses and bacteria that may invade the cell.

• HPS type 8: HPS type 8 is caused by mutations in the BLOC1S3 gene, which provides instructions for making the biogenesis of lysosome-related organelles complex-1 subunit 3 protein. This protein serves a similar function to the dysbindin protein in HSP type 7, in that it may be involved in the development of lysosomes.

Diagnosis

• General: Hermansky-Pudlak syndrome (HPS) can be diagnosed in infancy as albinism, which is characterized by decreased or absent pigment (coloring) in the skin, hair, and iris of the eyes. Its systemic manifestations unfold over time and are uncommon in childhood. Symptoms of inflammatory bowel disease occur between ages 12 and 30. The onset of pulmonary fibrosis begins in the third or fourth decade of life. Patients die of pulmonary fibrosis in the fourth or fifth decade of life. Pulmonary fibrosis, a disease of the lungs characterized by scarring of the lung tissue, can also be evaluated on physical examination. Physical findings relate to albinism, which affects the skin and the eyes.

• Physical exam: HPS may be suspected based on the observations of decreased or absent pigment in the hair and skin. Individuals suspected of having HPS should receive a thorough physical exam, including listening to the sounds of the lungs and heart. A complete family history should also be obtained. In addition, the patient or caregiver should be asked specific questions regarding the patient's bleeding history, including frequency of bruising, nosebleeds, and excessive bleeding associated with dental or other surgery, menstruation, or childbirth, as well as use of blood-thinning agents.

• Biopsy: In a biopsy, a small sample of tissue is removed and analyzed in a lab. To diagnose HPS, a skin biopsy may be taken to evaluate the number of cells containing the pigment melanin, a material that changes the color of light it reflects and provides color to hair, skin, and iris of the eyes. Individuals with HPS typically have deficits in melanin, which results in skin that ranges from white to olive and is generally noticeably lighter than that observed in unaffected family members. Freckles are common in individuals with HPS. Repeated exposure to the sun over the course of several years may cause skin to become rough and thick (called pachydermia) and may cause the development of precancerous and cancerous lesions. Melanin also absorbs ultraviolet light from the sun to protect the skin. Because melanin is absent or decreased in HPS, affected individuals are at increased risk of skin damage caused by the sun, including skin cancers such as basal cell and squamous cell carcinomas. As new growths develop on the skin, they may also be biopsied to assess whether they are harmless, precancerous, or cancerous.

• Blood test: Blood tests may be used to assess the number and quality of platelets, because individuals with HPS may have decreased levels or abnormally functioning platelets, the cells that help with clotting. Platelets may need to be examined using an electron microscope in order to detect the distinctive abnormality of HPS. The absence of DBs (referred to as chocolate chips) in the platelets is characteristic of this syndrome. A clinician may also measure clotting time. Clotting time may be longer than normal in people with HPS because of the decreased function of platelets.

• Bone densitometry: Some people with various types of albinism have abnormally low bone density. However, the role of bone density testing in individuals with HPS has not been well defined. Low bone density in individuals with albinism results in an increased risk of bone fracture. This symptom may be related to a genetic defect that occurs in albinism. Bone densitometry, an X-ray, may be used to measure bone density. Osteoporosis is diagnosed when the bone mineral density is a certain amount lower than that of a young adult reference population.

• Dermatologic exam: People suspected of having HPS should be examined by a dermatologist. This specialist can assess the quality of the skin and the presence of precancerous or cancerous lesions. Important points to cover include history of sun exposure, sun protection used, and a family and individual history of skin cancer.

• Eye exam: An eye exam, which includes several tests, can help diagnose HPS. In particular, an ophthalmologist should evaluate the condition of the retina in patients suspected of having HPS and also the presence of melanin, the color of the iris, nystagmus (involuntary movements of the eyes), astigmatism, visual clarity, strabismus (crossed eyes), and sensitivity to light. Ophthalmoscopic examination allows for observation of the internal structures of the eye, including the retina. Visual clarity is measured by asking an individual to read large and small letters on a chart.

• Hair bulb tyrosinase assay: A hair bulb tyrosinase assay can help distinguish HPS from other types of albinism. In this assay, hair bulbs or roots from the scalp are plucked and placed in a solution containing dihydroxyphenylalanine (L-DOPA). In people with oculocutaneous albinism (type 1 albinism), the hair bulb remains white. Hair bulbs from people with other forms of albinism, including HPS, turn dark.

• Imaging studies: Computed tomography (CT) scans of the lungs have been shown to be more effective than X-rays in assessing the presence and severity of pulmonary fibrosis, a scarring of the lungs that occurs in some individuals with HPS. MRI is a noninvasive imaging technique that uses magnetic and radio waves to create an image of tissues within the body. A CT scan is a noninvasive imaging technique that uses a series of X-rays to build a picture of the inside of the body.

• Pulmonary function tests: Pulmonary function tests (PFTs) can be used to assess the structure and function of the lungs. Typically, these tests require the use of a spirometer. In a spirometry test, the patient breathes into a mouthpiece connected to a spirometer. The spirometer records the amount and the rate of air that breathed in and out over a period of time. PFTs include forced vital capacity (FVC), which measures the amount of air a patient can exhale with force after a deep inhalation; forced expiratory volume (FEV), which measures the amount of air a patient can exhale with force in one breath; mean total lung capacity, which measures the amount of air in the lungs after a deep inhalation; slow vital capacity, which measures the amount of air a patient can slowly exhale after a deep inhalation; and mean diffusing capacity of the lung for carbon monoxide, which measures how well the lungs can transfer the carbon monoxide into the blood. Measurements acquired by these tests tend to be lower than normal in people with HPS who have developed fibrotic tissue, a scarring of the lung tissue.

• Genetic testing: For some types of HPS, deoxyribonucleic acid (DNA) tests can confirm a diagnosis of the disorder. A sample of the patient's blood is taken and analyzed in a laboratory for the defect in the HPS1, AP3B1 (HPS2), HPS3, HPS4, HPS5, HPS6, DTNBP1, or BLOC1S3 genes. If a defect is detected, a positive diagnosis is made.

• Prenatal DNA testing: If there is a family history of HPS, prenatal testing may be performed to determine whether the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose HPS. However, because there are serious risks associated with these tests, patients should discuss the potential health benefits and risks with a medical professional.

• During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.

• During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutated gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

Complications

• Blood loss: People with Hermansky-Pudlak syndrome (HPS) have platelet dysfunction and thus are prone to abnormal and excessive bleeding episodes, leading to thrombocytopenia (decreased clotting function during wound healing). Increased and abnormal bleeding is the cause of death in about 10-13% of individuals with HPS. The tendency for increased bleeding and poor clotting ability means that women with HPS are at risk for complications during childbirth, including a risk of bleeding to death if blood loss cannot be controlled. Increased bleeding may increase an individual's risk for developing anemia, a blood disorder characterized by low red blood cell counts.

• Bone fractures: Although not fully determined to be a characteristic of individuals with HPS, some individuals with albinism may be at risk for low bone density and consequent bone fractures.

• Cardiomyopathy: Accumulation of ceroid, a fatty substance, in the lungs, bowels, and heart, may cause people with HPS to develop a cardiomyopathy, a heart disease that involves inflammation of the heart muscle that impairs its function. Symptoms of this include buildup of fluid in the lungs or legs, fatigue, weakness, and shortness of breath.

• Colitis: People with HPS may develop inflammation and bleeding of the colon, also known as colitis, between 12 and 30 years of age. This condition tends to be severe in about 15% of people with HPS, some of whom require surgical removal of part of the intestine. While the colon is most often affected, inflammation and bleeding can occur in any part of the digestive tract, from the oral cavity to the anus. Symptoms of colitis may include abdominal pain, diarrhea, gastrointestinal bleeding, weight loss, and cramps. People of Puerto Rican heritage are particularly affected by colitis associated with HPS. Complications of colitis cause death in about 15% of people with HPS.

• Kidney disease: The accumulation of ceroid, a fatty substance, can cause progressive damage to the kidneys. This may result in scarring of the kidney tissue, which eventually prevents the kidneys from functioning properly and can ultimately lead to kidney failure.

• Lungs: People with HPS may have progressive development of fibrous tissue in the lungs during the third decade of life. Symptoms of pulmonary fibrosis include shortness of breath and abnormal fatigue. This condition may occur in anyone with HPS but has been noted specifically in individuals with HPS type 1 from northwestern Puerto Rico. Pulmonary fibrosis is the cause of death in about 50% of individuals with HPS.

• Psychosocial issues: Depending on the severity of the condition, people with HPS may experience psychosocial issues such as depression because of their unusual physical appearance.

• Skin cancer: Repeated exposure to the sun over the course of several years may cause skin to become rough and thick (called pachydermia) and may cause the development of precancerous and cancerous lesions. Melanin also absorbs ultraviolet light from the sun to protect the skin. Because melanin is absent or decreased in HPS, affected individuals are at increased risk of skin damage caused by the sun, including skin cancers such as basal cell and squamous cell carcinomas.

• Sunburn: People with albinism lack the pigment melanin, a material that changes the color of light it reflects and protects the skin from the harmful ultraviolet rays of the sun. This places them at higher risk of sunburn, even if sun exposure is brief.

• Vision problems: Because of a variety of eye problems, including abnormal curvature of the cornea and involuntary eye movements, people with certain types of albinism, including HPS, tend to have decreased visual clarity. Vision problems range from mild to severe, and degeneration of the retina may cause blindness.

Treatment

• General: There is no cure for Hermansky-Pudlak syndrome (HPS), which belongs to a group of disorders called albinism. Instead, treatment aims to reduce symptoms and prevent complications. Treatment may not be needed in many cases, for example, if the disorder appears as a skin condition without other symptoms. Depending on individual symptoms, people with HPS should be regularly examined by a dermatologist (skin doctor), ophthalmologist (eye doctor), hematologist (blood specialist), pulmonologist (lung specialist), gastroenterologist, geneticist or genetic counselor, and a gynecologist (specialist in women's health). Most patients with HPS (about 70%) die from complications related to the syndrome. Pulmonary fibrosis leads to death in almost 50% of patients with HPS, usually in the fourth decade of life. Bleeding leads to death in about 10% of patients with HPS. Other causes of death include intestinal, liver, and kidney failure. Since distinct differences in the symptoms for each type of HPS have not been determined, all types of HPS are treated using similar approaches.

• Antifibrotic medications: Studies are investigating the effect of the drug pirfenidone, which may prevent the development of fibrous tissue in people with pulmonary dysfunction. More studies are needed to determine safety and efficacy as well as applicability in people with HPS.

• Anti-inflammatory medications: Anti-inflammatory agents such as steroids may be used to treat colitis, an inflammation and bleeding of the colon.

• Corrective lenses: Visual clarity can be improved by the use of corrective lenses or glasses. In addition, sensitivity to bright light may be improved by wearing tinted lenses. In cases of severe visual impairment, bifocals or bioptics (telescopic lenses mounted on glasses) may be prescribed. Strabismus (crossed eyes) may be treated early in life by wearing a patch over one eye to promote the use of the less active eye.

• Diet: Although not fully determined to be a characteristic of individuals with HPS, some individuals with albinism may be at risk for osteoporosis (low bone density) and consequent bone fractures. A diet rich in calcium and vitamin D may be beneficial for those with HPS who have osteoporosis. This risk has not been specifically studied in individuals with HPS, and while safety does not seem to be a concern, the efficacy of such a diet is unknown.

• Heart medications: Angiotensin-converting enzyme (ACE) inhibitors, diuretics, digoxin, and beta-blockers may help with the management of cardiomyopathy and heart failure.

• Kidney dialysis: When the kidneys begin to fail, patients can undergo various types of dialysis to restore their filtering function. In hemodialysis, a patient's blood is circulated into an external filter and cleaned. The filtered blood is then returned to the body. In peritoneal dialysis, a fluid containing dextrose is introduced into the abdomen through a tube. This solution absorbs wastes in the body and is then removed.

• Kidney transplantation: Some patients who experience kidney failure may undergo kidney transplantation. An individual with end-stage renal disease (or ESRD) may receive a healthy kidney from either a living or a deceased donor. Transplantation is associated with complications, including infection and the possibility of rejection of the new organ. To reduce the chance of rejection, patients may need to take immunosuppressive drugs, such as tacrolimus (Prograf®), mycophenolate (CellCept®), prednisone, cyclosporine (Sandimmune®, Gengraf®, Neoral®), rapamycin (sirolimus, Rapamune®), or azathioprine (Imuran®). Cyclosporine, considered a breakthrough immunosuppressant when first discovered in the 1980s, ironically causes kidney toxicity and can result in damage to a newly transplanted kidney.

• MedicAlert®: People with HPS should wear a MedicAlert® bracelet to immediately alert healthcare personnel and other people to the risk of excessive bleeding associated with HPS. A MedicAlert® bracelet identifies the medical risk associated with the person wearing it.

• Medications to avoid: People with HPS should not use blood-thinning agents such as aspirin and warfarin (Coumadin®), an anticlotting medication. Individuals with HPS may have a decreased ability to clot after an injury, leading to excessive bleeding.

• Oral contraceptives: Oral contraceptive pills may reduce blood loss by reducing the duration of the menstrual period. Desmopressin (DDAVP®) may be provided by injection to improve clotting. This drug should not be used in individuals with allergy or hypersensitivity to desmopressin or in people with platelet-type von Willebrand disease.

• Oxygen therapy: If lung disease progresses, oxygen therapy may improve breathing and therefore quality of life. Individuals can be administered artificial oxygen through a mask.

• Patient education: People with HPS should be educated on how to best care for themselves. Patient and caregiver education for HPS should include the bleeding risks associated with playing contact sports and undergoing surgery, the importance of dental care, the avoidance of sun exposure, the use of sun protection, and the availability of various adaptive visual tools to enhance learning, participation in activities, and quality of life. This information can be obtained through healthcare professionals.

• Psychotherapy: Psychotherapy is an interactive process between an individual and a qualified mental health professional (e.g., a psychiatrist, psychologist, clinical social worker, licensed counselor, or other trained practitioner). Its purpose is the exploration of thoughts, feelings, and behavior for the purpose of problem solving or achieving higher levels of functioning. This process may be helpful for individuals who may experience psychosocial issues such as depression because of their unusual physical appearance.

• Skin care: Minor cuts that fail to clot should be treated with a thrombin-soaked gel form, a sponge that contains thrombin, a protein that promotes clotting. Home humidifiers may reduce the incidence of nosebleeds. Skin softeners such as petroleum or mineral oil and retinoids, derivatives of vitamin A, such as Retin-A® may improve the appearance and texture of skin. Although there is no cure for sunburn, the application of aloe may soothe the skin.

• Smoking cessation: Because of their susceptibility to lung problems, individuals with HPS should be advised to quit smoking.

• Sunscreen: There is no treatment for lack of pigment in the skin of people who have HPS. However, because they are at increased risk for sunburn and skin cancer, people with HPS should wear a broad-spectrum sunscreen on all exposed areas of the body, including the scalp. Clothing that increases protection from the sun is also available and includes hats, visors, long-sleeve shirts, and long pants.

• Surgery: In severe cases, eye muscle surgery may be done to treat nystagmus (involuntary eye movements) or strabismus (crossed eyes). For those patients who develop skin cancer, traditional treatments would apply and include surgery, radiation therapy, and chemotherapy.

• Surgical precautions: Because of the increased risk of bleeding, individuals with HPS who have planned surgery should meet with a hematologist (blood specialist), anesthesiologist, and surgeon beforehand.

• Transfusions: People with HPS may require transfusions of whole blood or platelets to replace lost blood. Frequent blood transfusions carry the risk of acquiring viral diseases, such as hepatitis, and iron toxicity. During a blood transfusion, the blood of a donor is transferred into the recipient intravenously, or through a vein. A 500-milliliter unit of blood is administered over four hours.

• Visual aids: Various visual aids can be used to meet the individual needs of people with HPS. These may include large-print books and other reading materials, high-contrast written materials, monoculars, video enlargement machines, and other types of magnifiers. In addition, children and adults attending school may benefit from a printed copy of the teacher's board notes. People with albinism may also benefit from various specialized computer programs that address their individual needs.

Integrative Therapies

• Note: Currently there is limited scientific evidence on the use of integrative therapies for the treatment or prevention of Hermansky-Pudlak syndrome (HPS). The therapies listed below have been studied for related conditions such as sunburn and skin cancer. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies.

• Unclear or conflicting scientific evidence:

• Chlorella: Early studies suggest a potential effect of chlorella on skin cancer. Avoid with known allergy or hypersensitivity to chlorella, its constituents, or members of the Oocystaceae family. Children have been found to be allergic to chlorella. Chlorella has a high vitamin K content and may decrease the effectiveness of anticoagulants (blood thinners) such as warfarin. Long-term consumption of chlorella may cause manganese-induced parkinsonism. Other adverse effects include photosensitivity, occupational asthma, and fatigue.

• Green tea: There is limited animal and human research on green tea as a protective agent from ultraviolet light injury to the skin. Some studies have found conflicting results. Comparisons have not been made with well-established forms of sun protection such as ultraviolet-protective sunscreen. The effects of green tea on skin damage caused by the sun remain unclear. Avoid if allergic or hypersensitive to caffeine or tannin. Use cautiously with diabetes or liver disease.

• Lutein: Numerous laboratory studies have shown the antioxidant effect of lutein. More research is required on the use of lutein for sunburn prevention before a firm conclusion can be made. Avoid if allergic or hypersensitive to lutein or zeaxanthin. Use cautiously if at risk for cardiovascular disease or cancer. Avoid if pregnant or breastfeeding.

• Lycopene: Lycopene, in combination with other carotenoids, such as beta-carotene, vitamins C and E, selenium, and proanthocyanidins, may help in reducing sunburn. Selected protective effects from ultraviolet (UV) rays have been observed in small short-term studies. More research is needed before a firm conclusion can be drawn. Avoid if allergic to tomatoes or to lycopene. Avoid if pregnant or breastfeeding.

• Para-aminobenzoic acid (PABA): PABA is best known for its topical use as a component of sunscreen products. Although PABA and related compounds have frequently been used as topical sunscreen agents, only a few studies in the literature have demonstrated its effectiveness for this specific purpose. Further studies may help to elucidate the protective properties of PABA. Its use as a component of sunscreens has diminished recently because of reports of frequent allergic reactions and cross-sensitivity with other medications.

• Pycnogenol®: Pycnogenol® taken by mouth may reduce redness of the skin caused by solar ultraviolet light. Further research is needed before a recommendation can be made. Avoid if allergic or hypersensitive to Pycnogenol®, its components, or members of the Pinaceae family. Use cautiously with diabetes, hypoglycemia, or bleeding disorders. Use cautiously if taking medications that reduce blood cholesterol levels, medications that may increase the risk of bleeding, medications that lower blood pressure, or drugs that affect the immune system. Avoid if pregnant or breastfeeding.

• Selenium: Protection from UV damage was initially observed in early research using selenium and other antioxidant supplementation, although there is some evidence that selenium does not prevent light-induced skin redness. Avoid if allergic or sensitive to products containing selenium. Avoid with history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.

• Vitamin A: It is unclear whether vitamin A or beta-carotene, taken by mouth or used on the skin with sunscreen, is beneficial in the prevention or treatment of skin cancers or wrinkles. Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity can occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses. However, excess or inadequate vitamin A has been associated with birth defects. Excessive doses of vitamin A have been associated with central nervous system problems. Use cautiously if breastfeeding, because the benefits or dangers to nursing infants have not been clearly established.

• Fair negative scientific evidence:

• Selenium: Results from the Nutritional Prevention of Cancer (NPC) trial, conducted among 1,312 Americans over a 13-year period, suggest that selenium supplementation given to individuals at high risk of nonmelanoma skin cancer is ineffective in the prevention of basal cell carcinoma and actually increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer. Therefore, selenium supplementation should be avoided in individuals at risk for or with a history of nonmelanoma skin cancer. Avoid if allergic or sensitive to products containing selenium. Avoid with a history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.

Prevention

• General: Because Hermansky-Pudlak syndrome (HPS) is inherited, or passed down among family members, there is currently no known way to prevent the condition. However, a number of options are available for prospective parents with a family history of HPS.

• Genetic testing and counseling: Individuals who have HPS may meet with a genetic counselor to discuss the risks of having children with the disease and to determine whether they carry the defective genes. Carriers can be determined through detailed family histories or genetic testing.

• Known carriers of genes that cause HPS may undergo genetic counseling before they conceive a child. Genetic counselors can explain the options and the associated risks of various tests, including amniocentesis, chorionic villus sampling (CVS), and preimplantation genetic diagnosis (PGD).

• During amniocentesis, a long, thin needle is inserted through the abdominal wall and into the uterus, and a small amount of amniotic fluid is removed from the sac surrounding the fetus. Cells in the fluid are then analyzed for normal and abnormal chromosomes. This test is performed after 15 weeks of pregnancy. The risk of miscarriage is about one in 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.

• During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta between the ninth and 14th weeks of pregnancy. CVS may be performed through the cervix or through the abdomen. The cells in the tissue sample are then analyzed for the mutated gene. Miscarriage occurs in about 0.5-1% of women who undergo this procedure.

• Preimplantation genetic diagnosis (PGD) may be used with in vitro (artificial) fertilization. In PGD, embryos are tested for the defective genes, and only the embryos that are not affected may be selected for implantation. Because HPS may be detected in fetus, parents may choose whether to continue the pregnancy. Genetic counselors may assist parents with these difficult decisions.

• MedicAlert®: People with HPS should wear a MedicAlert® bracelet to immediately alert healthcare personnel and other people to the risk of excessive bleeding associated with HPS. A MedicAlert® bracelet identifies the medical risk associated with the person who is wearing it.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Avila NA, Brantly M, Premkumar A, et al. Hermansky-Pudlak syndrome: radiography and CT of the chest compared with pulmonary function tests and genetic studies. AJR Am J Roentgenol. 2002;179(4):887-92. View Abstract

2. Badolato R, Parolini S. Novel insights from adaptor protein 3 complex deficiency. J Allergy Clin Immunol. 2007;120(4):735-41; quiz 742-3. View Abstract

3. Boissy RE, Richmond B, Huizing M, et al. Melanocyte-specific proteins are aberrantly trafficked in melanocytes of Hermansky-Pudlak syndrome-type 3. Am J Pathol. 2005;166(1):231-40. View Abstract

4. Brantly M, Avila NA, Shotelersuk V, et al. Pulmonary function and high-resolution CT findings in patients with an inherited form of pulmonary fibrosis, Hermansky-Pudlak syndrome, due to mutations in HPS-1. Chest. 2000;117(1):129-36. View Abstract

5. Chiang PW, Oiso N, Gautam R, et al. The Hermansky-Pudlak syndrome 1 (HPS1) and HPS4 proteins are components of two complexes, BLOC-3 and BLOC-4, involved in the biogenesis of lysosome-related organelles. J Biol Chem. 2003;278(22):20332-7. View Abstract

6. Cordova A, Barrios NJ, Ortiz I, et al. Poor response to desmopressin acetate (DDAVP) in children with Hermansky-Pudlak syndrome. Pediatr Blood Cancer. 2005;44(1):51-4. View Abstract

7. Davies BH, Tuddenham EG. Familial pulmonary fibrosis associated with oculocutaneous albinism and platelet function defect. A new syndrome. Q J Med. 1976;45(178):219-32. View Abstract

8. Di Pietro SM, Falcón-Pérez JM, Dell'Angelica EC. Characterization of BLOC-2, a complex containing the Hermansky-Pudlak syndrome proteins HPS3, HPS5 and HPS6. Traffic. 2004;5(4):276-83. View Abstract

9. Dimson O, Drolet BA, Esterly NB. Hermansky-Pudlak syndrome. Pediatr Dermatol. 1999;16(6):475-7. View Abstract

10. Enders A, Zieger B, Schwarz K, et al. Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II. Blood. 2006;108(1):81-7. View Abstract

11. Erzin Y, Cosgun S, Dobrucali A, et al. Complicated granulomatous colitis in a patient with Hermansky-Pudlak syndrome, successfully treated with infliximab. Acta Gastroenterol Belg. 2006;69(2):213-6. View Abstract

12. Feliciano NZ, Rivera E, Agrait E, et al. Hermansky-Pudlak syndrome: dental management considerations. J Dent Child (Chic). 2006;73(1):51-6. View Abstract

13. Feng L, Novak EK, Hartnell LM, et al. The Hermansky-Pudlak syndrome 1 (HPS1) and HPS2 genes independently contribute to the production and function of platelet dense granules, melanosomes, and lysosomes. Blood. 2002;99(5):1651-8. View Abstract

14. Grucela AL, Patel P, Goldstein E, et al. Granulomatous enterocolitis associated with Hermansky-Pudlak syndrome. Am J Gastroenterol. 2006;101(9):2090-5. View Abstract

15. Hazzan D, Seward S, Stock H, et al. Crohn's-like colitis, enterocolitis and perianal disease in Hermansky-Pudlak syndrome. Colorectal Dis. 2006;8(7):539-43. View Abstract

16. Hermansky-Pudlak Syndrome Network. www.hpsnetwork.org.

17. Hermos CR, Huizing M, Kaiser-Kupfer MI, et al. Hermansky-Pudlak syndrome type 1: gene organization, novel mutations, and clinical-molecular review of non-Puerto Rican cases. Hum Mutat. 2002;20(6):482. View Abstract

18. Iannello S, Fabbri G, Bosco P, et al. A clinical variant of familial Hermansky-Pudlak syndrome. MedGenMed. 2003;5(1):3. View Abstract

19. Izquierdo NJ, Emanuelli A, Izquierdo JC, et al. Foveal thickness and macular volume in patients with oculocutaneous albinism. Retina. 2007;27(9):1227-30. View Abstract

20. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com.

21. Schreyer-Shafir N, Huizing M, Anikster Y, et al. A new genetic isolate with a unique phenotype of syndromic oculocutaneous albinism: clinical, molecular, and cellular characteristics. Hum Mutat. 2006;27(11):1158. View Abstract