Introduction
Hermansky-pudlak syndrome is an autosomal recessive disorder. It is a genetic disorder that affects multiple systems in the human body. It causes skin damage, visual problems, problems with blood clotting, breathing problems, swelling of the large intestine, and kidney failure. It can affect the lungs, kidneys, intestines, and heart.
What Is Hermansky-Pudlak Syndrome?
Hermansky-pudlak syndrome is a genetic disorder. It causes oculocutaneous albinism (reduced pigmentation), bleeding problems due to platelet storage pool defect, and storage of abnormal fat-protein compounds due to lysosomal accumulation of ceroid lipofuscin. It is also referred to as albinism with hemorrhagic diathesis and reticuloendothelial cells, and delta storage pool disease.
What Are the Causes of Hermansky-pudlak Syndrome?
Genetic mutations cause it. It is caused by mutations in HPS1, HPS3, HPS4, HPS5, HPS6, and HPS7 (Hermansky-pudlak syndrome) genes. HPS type 2 is caused by AP3B1 (adaptor-related protein complex three subunit beta 1) gene mutation. It includes immunodeficiency in its phenotype. HPS type 7 is caused by a mutation in the gene coding for the dysbindin protein. It is an autosomal recessive disorder caused by the defective gene HSP, located on the long arm of chromosome 10. Autosomal recessive disorder is a condition in which the two copies of the defective gene, one from each parent, are responsible for the disorder. The person becomes a disease carrier if the person receives one normal gene and one defective gene. Abnormality in the lysosomal function may be responsible for the development of this syndrome. This syndrome is associated with HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, and biogenesis of lysosome-related organelles complex (BLOC1, BLOC1S2, and BLOC3).
How Does Hermansky-pudlak Syndrome Occur?
It is characterized by the abnormal accumulation of platelets with thrombin, epinephrine, and adenosine diphosphate. The platelets have lesser amounts of dense bodies. Pulmonary fibrosis, granulomatous colitis, cardiomyopathy, and renal failure occur due to the biogenesis of lysosome-related organelles. Ceroid lipofuscin, a lipid-protein material, accumulates in the lysosomes of HPS cells, renal tubular cells, alveolar macrophages, cells of the gastrointestinal tract, bone marrow, liver, spleen, lymph nodes, and heart.
What Are the Signs and Symptoms of Hermansky-pudlak Syndrome?
This disease is characterized by oculocutaneous albinism, bleeding diathesis, and involvement of other organs. The signs and symptoms include:
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Eyes - Children with this syndrome have nystagmus at birth. Wandering eye movements and lack of attention are also present. Photophobia and severe foveal hypoplasia are noticed. Iris color appears as blue or green, or brown or tan color. Pigmentation develops in the retina, appearing as streaks of pigment or clumps. Visual acuity and alternating strabismus are present.
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Skin or Hair - The hair appears white or brown. Skin appears white to olive in color. Exposure to the sun results in coarse, rough, and thickened skin, leading to solar keratoses and skin cancer, including basal and squamous cell carcinoma. Actinic keratoses, nevi, ephelides, and lentigines can occur.
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Bleeding Diathesis - It occurs due to absent or deficient granules in platelets. This results in bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding during menstruation, tooth extraction, circumcision, or other surgeries.
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Pulmonary Fibrosis - It is a progressive lung disease. The lung tissues become thicker and make it difficult to breathe. It is a fatal condition that cannot be cured.
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Colitis - It causes bleeding and resembles Crohn's disease. It presents with inflammatory bowel disease. The alimentary tract, including the gingiva, can also be affected.
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Neutropenia - This syndrome is associated with low levels of neutrophils. It is due to the AP3 deficient HPS, with variants in AP3B1 or AP3D1.
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Cellular Storage Disorders - This syndrome causes the accumulation of a wax-like substance called
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Ceroid in the body tissues damages the lungs and kidneys.
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Others - Cardiomyopathy and renal failure can also occur.
How To Prevent Complications?
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Protection from sun exposure.
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Wearing a medical alert bracelet to monitor platelet function.
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Improving pulmonary function.
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Immunization with influenza and pneumococcal vaccines.
How Is Hermansky-pudlak Syndrome Diagnosed?
The diagnosis is based on clinical findings, electron microscopic examination of platelets, and molecular genetic testing.
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Clinical Findings - Features like nystagmus, wandering eye movements, lack of visual attention, skin and hair color, gingival bleeding, and prolonged bleeding after minor surgical procedures suggest Hermansky-pudlak syndrome.
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Laboratory Findings - Impaired secondary aggregation response during platelet aggregation test, normal prothrombin time, partial prothrombin time, normal platelet count, prolonged bleeding time, and absence of dense platelet bodies are the laboratory findings of this syndrome. Four to eight dense bodies are present per platelet in normal conditions, whereas dense bodies in platelets are absent in individuals with this syndrome.
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Molecular Genetic Testing - Serial single-gene testing, multigene panel, or comprehensive genomic testing are done to identify the pathologic variants. Comprehensive genomic testing, including exome and genome sequencing, should be considered because many genes are associated with this syndrome.
How Is Hermansky-pudlak Syndrome Treated?
The treatment for Hermansky-pudlak syndrome involves symptomatic management.
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Eyes - Individuals with albinism present with hyperopia (far-sight), myopia (short-sight), and astigmatism. These refractive errors are corrected to improve visual acuity. Strabismus surgery is performed for cosmetic reasons. Magnifying devices or bioptic lenses are useful for improving vision.
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Bleeding - Humidifiers are used to reduce the frequency of nosebleeds. Oral contraceptives are given to reduce the duration of the menstrual cycle. Levonorgestrel-releasing intrauterine system and recombinant factor VIIa are used to treat menorrhagia. Thrombin-soaked gel forms are placed over minor cuts to promote clotting. DDAVP (1-des amino-8-D-arginine vasopressin) is given as a 30-minute intravenous infusion before invasive procedures like tooth extraction. Platelet or red blood cell transfusions are required for extensive surgical procedures.
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Pulmonary Fibrosis - Oxygen therapy is required in severe cases. Single or bilateral lung transplants are required for severe cases of pulmonary fibrosis.
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Colitis - Steroids and anti-inflammatory agents are given to treat granulomatous colitis.
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Immunodeficiency - Granulocyte colony-stimulating factor is given to treat immunodeficiency in HPS syndrome.
Conclusion
Hermansky-pudlak syndrome is a rare genetic disorder that affects multiple systems of the human body. Pulmonary fibrosis associated with this syndrome is also a rare condition. The diagnosis of this syndrome depends on clinical findings and genetic testing. Early diagnosis helps in the treatment and prevents the risk of complications.
