Hermansky–Pudlak syndrome
Other names: Albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells[1], Delta storage pool disease
Hermansky–Pudlak syndrome is inherited via autosomal recessive manner

Heřmanský–Pudlák syndrome (often writtenHermansky–Pudlak syndrome or abbreviatedHPS) is an extremely rareautosomalrecessive^[2] disorder which results inoculocutaneous albinism (decreasedpigmentation), bleeding problems due to aplatelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin). It is considered to affect around 1 in 500,000 people worldwide, with a significantly higher occurrence inPuerto Ricans, with a prevalence of 1 in 1800.^[3] Many of the clinical research studies on the disease have been conducted in Puerto Rico.

There are eight classic forms of the disorder, based on thegeneticmutation from which the disorder stems.^[4]

Signs and symptoms

There are three main disorders caused by Hermansky–Pudlak syndrome, which result in these symptoms:

• Albinism and eye problems: Individuals will have varying amounts of skin pigment (melanin). Because of the albinism there are eye problems such as light sensitivity (photophobia), strabismus (crossed eyes), and nystagmus (involuntary eye movements). Hermansky–Pudlak syndrome also impairs vision.^{[citation needed]}
• Bleeding disorders: Individuals with the syndrome have platelet dysfunction. Since platelets are necessary for blood clotting, individuals will bruise and bleed easily.^{[citation needed]}
• Cellular storage disorders: The syndrome causes a wax-like substance (ceroid) to accumulate in the body tissues and cause damage, especially in the lungs and kidneys.^[5]

It is also associated withgranulomatouscolitis,^{[citation needed]}, an inflammation of the colon, and with pulmonary fibrosis,^{[citation needed]} a potentially fatal lung disease.

Causes

HPS can be caused bymutations in severalgenes:HPS1,HPS3,HPS4,HPS5,HPS6 andHPS7.^{[citation needed]}

HPS type 2, which includes immunodeficiency in its phenotype, is caused by mutation in theAP3B1 gene.^{[citation needed]}

HPS type 7 may result from a mutation in the gene coding fordysbindin protein.^[6]

Hermansky–Pudlak syndrome is thought to be inherited as an autosomal recessive genetic trait. The defective gene, called HSP^{[dubious –discuss]}, responsible for this disorder is located on the long arm ofchromosome 10 (10q2). Some research suggests that an abnormality of lysosomal function may be responsible for the development of the disease.

HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6,DTNBP1 and Biogenesis of Lysosome-related Organelles Complex (BLOC1,BLOC1S2 andBLOC3) are associated with Hermansky–Pudlak syndrome.^{[citation needed]}

In autosomal recessive disorders, the condition does not appear unless a person inherits two copies of the defective gene responsible for the disorder, one copy coming from each parent. If an individual receives one normal gene and one gene for the disorder, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.^[7]

Pathophysiology

The mechanism of Hermansky–Pudlak syndrome indicates thatplatelets in affected individuals accumulate abnormally withthrombin,epinephrine, andadenosine diphosphate, furthermore platelets in these individuals have a lower amount of dense bodies^[9]

Diagnosis

The diagnosis of HPS is established by clinical findings of hypopigmentationof the skin and hair, characteristic eye findings, and demonstration of absentdense bodies on whole mount electron microscopy of platelets. Moleculargenetic testing of the HPS1 gene is available on a clinical basis forindividuals from northwestern Puerto Rico. Molecular testing of the HPS3 geneis available on a clinical basis for individuals of central Puerto Rican orAshkenazi Jewish heritage. Sequence analysis is available on a clinical basisfor mutations in HPS1 and HPS4. Diagnosis of individuals with other types ofHPS is available on a research basis only.^[10]

Treatment

While there is no cure for HPS, treatment for chronichemorrhages associated with the disorder includes therapy withvitamin E and the antidiureticdDAVP.^[11]

Considerations for patients

A preoperative pulmonology consultation is needed. The anesthesia team shouldbe aware that patients may have postoperative pulmonary complications as partof the syndrome.^{[citation needed]}

Preoperative hematology consultation is advisable prior to elective ocularsurgeries. Since patients with the syndrome have bleeding tendencies,intraoperative, perioperative, and postoperative hemorrhages should beprevented and treated. If platelet aggregation improves with desmopressin, itmay be administered in the preoperative period. However, sometimesplasmapheresis is needed in the perioperative period.^{[citation needed]}

Ophthalmologists should try to avoid retrobulbar blocks in patients with thesyndrome. Whenever possible, patients with HPS may benefit from generalendotracheal anesthesia. Phacoemulsification may help prevent intraoperativeand postoperative bleeding in patients with the syndrome. Prolonged bleedinghas been reported following strabismus surgery in patients with the syndrome.^[12]

Prognosis

The course of HPS has been mild in rare instances of the disorder,^[13] however, the general prognosis is still considered to be poor.^{[citation needed]}The disease can cause dysfunctions of thelungs,intestine,kidneys, andheart. The major complication of most forms of the disorder ispulmonary fibrosis, which typically exhibits in patients ages 40–50 years.^[14] This is a fatal complication seen in many forms of HPS, and is the usual cause of death from the disorder.^[15] HPS patients who develop pulmonary fibrosis typically have type 1 or type 4.^{[citation needed]}

Research

HPS is one of the rare lung diseases currently being studied by The Rare Lung Diseases Consortium (RLDC). The RLDC is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), of the National Center for Advancing Translational Sciences (NCATS). The RLDC is dedicated to developing new diagnostics and therapeutics for patients with rare lung diseases, through collaboration between the NIH, patient organizations and clinical investigators.^{[citation needed]}

Society

Hermansky–Pudlak syndrome patients, families, and caregivers are encouraged to join theNIH Rare Lung Diseases Consortium Contact RegistryArchived 27 March 2019 at theWayback Machine. This is a privacy protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases.^{[citation needed]}

Eponym

It is named forFrantišek Heřmanský (1916–1980) andPavel Pudlák (1927–1993).^[16][17][18]

See also

• Biogenesis of lysosome-related organelles complex 1
• List of cutaneous conditions

References

External links

• GeneReviews/NCBI/NIH/UW entry on Hermansky-Pudlak SyndromeArchived 9 April 2010 at theWayback Machine

• Pages with script errors
• CS1 maint: unflagged free DOI
• CS1 errors: missing periodical
• All articles with dead external links
• Articles with dead external links from April 2017
• Articles with invalid date parameter in template
• Articles with permanently dead external links
• Use dmy dates from July 2013
• All articles with unsourced statements
• Articles with unsourced statements from February 2016
• Articles with unsourced statements from October 2017
• All accuracy disputes
• Articles with disputed statements from January 2016
• Webarchive template wayback links
• Articles with unsourced statements from July 2020
• Disturbances of human pigmentation
• Syndromes affecting the skin
• Amino acid metabolism disorders
• Autosomal recessive disorders
• Rare syndromes
• Coagulopathies
• IUIS-PID table 3 immunodeficiencies
• Syndromes affecting blood
• Syndromes affecting the lung