Clinical Diagnosis

The diagnosis of Hermansky-Pudlak syndrome (HPS) is established by clinical findings of oculocutaneous albinism in combination with a bleeding diathesis of variable severity [Gahl et al 1998].

The diagnosis of oculocutaneous albinism is established by finding hypopigmentation of the skin and hair on physical examination associated with the following characteristic ocular findings:

• Nystagmus

• Reduced iris pigment with iris transillumination

• Reduced retinal pigment on fundoscopic examination

• Foveal hypoplasia associated with significant reduction in visual acuity

• Increased crossing of the optic nerve fibers [King et al 2001]

Testing

Absence of platelet dense bodies. Currently, the sine qua non for diagnosis of HPS is absence of dense bodies on whole mount electron microscopy of platelets [Witkop et al 1987]. Upon stimulation of platelets, the dense bodies, which contain ADP, ATP, serotonin, calcium, and phosphate, release their contents to attract other platelets. This process constitutes the secondary aggregation response, which cannot occur in the absence of the dense bodies. There are normally four to eight dense bodies per platelet; there are none in the platelets of individuals with HPS.

Coagulation studies

• The secondary aggregation response of platelets is impaired.

• Bleeding time is generally prolonged.

• Coagulation factor activity and platelet counts are normal.

Ceroid lipofuscin. The demonstration of a yellow, autofluorescent, amorphous lipid-protein complex, called ceroid lipofuscin, in urinary sediment and parenchymal cells is characteristic of HPS; however, this laboratory finding is virtually never used in diagnosis.

Molecular Genetic Testing

Genes. The HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, and BLOC1S3 genes are known to be associated with HPS.

Other loci. Most likely, mutations in other genes also result in HPS.

Clinical testing

• Targeted mutation analysis

  • HPS1. Homozygosity for a 16-bp duplication is found in approximately 75% of all affected individuals of Puerto Rican ancestry [Santiago Borrero et al 2006] and in virtually all affected individuals from northwestern Puerto Rico [Oh et al 1996, Huizing & Gahl 2002]. To date, the 16-bp duplication has been found exclusively in affected individuals of Puerto Rican ancestry. This duplication is designated c.1470_1486dupCCAGCAGGGGAGGCCC, (or c.1470_1486dup16).

  • HPS3. Homozygosity for g.339_4260del3904, (also referred to as the 3.9-kb deletion) has been identified in affected individuals of Puerto Rican ancestry only [Anikster et al 2001]. Homozygosity for c.1303+1G>A (also known as 1163+1G>A) splice site mutation has been identified in affected individuals of Ashkenazi Jewish ancestry only [Huizing et al 2001a].

• Sequence analysis

  • HPS1. The HPS1 gene is mutated in virtually all affected individuals from northwestern Puerto Rico and in approximately 50% of affected non-Puerto Ricans [Oh et al 1996, Oh et al 1998, Shotelersuk & Gahl 1998, Shotelersuk et al 1998, Oetting & King 1999, Hermos et al 2002, Huizing & Gahl 2002]. Homozygotes as well as compound heterozygotes for HPS1 mutations have been identified.

  • AP3B1 (HPS2). Mutations in the AP3B1 gene have been identified in several individuals: two adult brothers [Dell'Angelica et al 1999], a six-year-old boy [Huizing et al 2002], another child [Clark et al 2003], two siblings with consanguineous Turkish parents [Jung et al 2006], two Italian siblings [Fontana et al 2006], and a child originally diagnosed with Griscelli syndrome [Enders et al 2006].

  • HPS3. Sequence analysis of patients known to have HPS is expected to identify mutations in HPS3 about 15% of the time. In addition to novel mutations, sequence analysis will identify individuals with HPS who are of Ashkenazi Jewish background with the c.1303+1G>A splice site mutation [Huizing et al 2001a]. Of six individuals with this mutation, four were homozygotes and two were compound heterozygotes.

  • HPS4. Mutations in the gene HPS4 have been reported in 15 affected individuals [Suzuki et al 2002, Anderson et al 2003], including a Sri Lankan [Bachli et al 2004].

  • HPS5. Mutations in HPS5 have been found in five individuals. The mutations include a homozygous four-base deletion in a three-year-old Turkish boy [Zhang et al 2003], homozygous missense mutations in 51- and 43-year-old sisters of Swiss extraction [Huizing et al 2004], compound heterozygous insertions in a 21-year-old woman of English and Irish background [Huizing et al 2004], and compound heterozygous deletion/nonsense mutations in a ten-year-old boy of English, Irish, Dutch, and Swedish background [Huizing et al 2004].

  • HPS6. Five individuals with eight different mutations in HPS6 have been reported [Zhang et al 2003, Huizing et al 2009].

  • DTNBP1 (HPS7). About 1% of individuals with HPS have mutations in DTNBP1. A homozygous nonsense mutation in DTNBP1 has been reported in a single person, a 48-year old Portuguese woman with HPS7.

  • BLOC1S3 (HPS8). A single family in Britain was identified with a homozygous frameshift mutation in BLOC1S3 [Morgan et al 2006].

Table 1. Summary of Molecular Genetic Testing Used in HPS

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Gene Symbol (Locus)	Proportion of HPS Attributed to Mutations in This Gene		Test Method	Mutations Detected	Mutation Detection Frequency 1	Test Availability
	Puerto Rican	Non-Puerto Rican
HPS1	~75%	0%	Targeted mutation analysis	c.1470_1486dup CCAGCAGGGGAGGCCC (16-bp duplication)	100% for the targeted variant	Clinical
		50%	Sequence analysis	Sequence variants 2	Unknown
AP3B1 (HPS2)	0	~6%	Sequence analysis	Sequence variants 2	Unknown	Clinical
HPS3	25%	?	Targeted mutation analysis	g.339_4260del3904	~100% for the targeted variant	Clinical
		~5% 3		c.1303+1G>A	~100% for the targeted variant
	0	~15%	Sequence analysis	Sequence variants 2 (other than c.1303+1G>A	Unknown
HPS4	0	~12%	Sequence analysis	Sequence variants 2	Unknown	Clinical
HPS5	0	~5%	Sequence analysis	Sequence variants 2	Unknown	Clinical
HPS6	0	~4%	Sequence analysis	Sequence variants 2	Unknown	Clinical
DTNBP1 (HSP7)	0	~1%	Sequence analysis	Sequence variants 2	Unknown	Clinical
BLOC1S3 (HPS8)	0	2%	Sequence analysis	Sequence variants 2	Unknown	Clinical

Test Availability refers to availability in the GeneTests Laboratory Directory. GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.

1. The ability of the test method used to detect a mutation that is present in the indicated gene

2. Small intragenic deletions/insertions, missense, nonsense, and splice site mutations

3. Individuals of Ashkenazi Jewish ancestry

Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

To confirm/establish the diagnosis in a proband presumably manifesting signs of oculocutaneous albinism and bleeding:

• Electron microscopy of platelets to show absent dense bodies should be performed to confirm the diagnosis of HPS.

• In a person of northwest Puerto Rican ancestry, the HPS1 founder mutation should be pursued next.

• In a person of central Puerto Rican or Ashkenazi Jewish ancestry, the HPS3 founder mutations should be investigated.

• For other individuals, the order of testing can depend on the severity of clinical findings; visual acuity provides a rough measure of severity:

  • Severely affected individuals can be tested for HPS1 and HPS4 mutations initially.

  • Mildly affected individuals can be tested for HPS3, HPS5, or HPS6 mutations.

  • If a patient had neutropenia or infections as a child, the AP3B1 gene should be considered.

  • If all other HPS gene testing is negative, testing for mutations in DTNBP1 (HPS7) and BLOC1S3 (HPS8) should be considered.

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in the family.

Note: Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutations in the family.

Genetically Related (Allelic) Disorders

No other phenotypes are known to be caused by mutations in HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, or BLOC1S3.

Natural History

The clinical characteristics of Hermansky-Pudlak syndrome (HPS) consist of oculocutaneous albinism, a bleeding diathesis, a platelet storage pool deficiency, and other organ involvement [Huizing et al 2001b, Huizing & Gahl 2002]. Signs and symptoms of oculocutaneous albinism in HPS are variable but visual acuity generally remains stable.

Eyes. Nearly all children with the albinism of HPS have nystagmus at birth, often noticed by the parents in the delivery room and by the examining physician. Children with HPS may also have periodic alternating nystagmus [Gradstein et al 2005], wandering eye movements, and lack of visual attention. The initial diagnosis of albinism is sometimes made by the ophthalmologist.

The nystagmus can be very fast early in life, and generally slows with time, but nearly all individuals with albinism have nystagmus throughout their lives. The development of pigment in the iris or retina does not affect the nystagmus. Nystagmus is most noticeable when an individual is tired or anxious, and less marked when s/he is well rested and relaxed.

Photophobia may accompany severe foveal hypoplasia.

Iris color may remain blue or change to a green/hazel or brown/tan color. Globe transillumination can be complete or can show peripupillary clumps or streaks of pigment in the iris that appear like spokes of a wagon wheel. Fine granular pigment may develop in the retina.

Visual acuity, usually between 20/50 and 20/400, is typically 20/200 and usually remains constant after early childhood [Iwata et al 2000].

Alternating strabismus is found in many individuals with albinism and is generally not associated with the development of amblyopia.

Skin/hair. The hair color ranges from white to brown, and can occasionally darken with age. Skin color can be white to olive, but is generally at least a shade lighter than that of other family members.

Over many years, exposure to the sun of lightly pigmented skin can result in coarse, rough, thickened skin (pachydermia), solar keratoses (premalignant lesions), and skin cancer. Both basal cell carcinoma and squamous cell carcinoma can develop. Although skin melanocytes are present in individuals with HPS, melanoma is rare.

Affected Puerto Ricans typically have solar damage manifesting as actinic keratoses and nevi. Ephelids, lentigines, and basal cell carcinoma also occur with increased frequency among Puerto Ricans with HPS [Toro et al 1999].

Bleeding diathesis. The bleeding diathesis of HPS results from absent or severely deficient dense granules in platelets; the alpha granule contingent is normal [Huizing et al 2007]. Affected individuals experience variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding during menstruation or after tooth extraction, circumcision, or other surgeries. Typically, cuts bleed longer than usual but heal normally. Bruising generally first appears at the time of ambulation. Epistaxis occurs in childhood and diminishes after adolescence. Menstrual cycles may be heavy and irregular. Prolonged bleeding after tooth extraction can lead to the diagnosis of HPS. Affected individuals with colitis may bleed excessively per rectum. Exsanguination as a complication of childbirth, trauma, or surgery is extremely rare.

Pulmonary fibrosis. The pulmonary fibrosis of HPS typically causes symptoms in the thirties and is usually fatal within a decade. The pulmonary fibrosis has been described largely in individuals with HPS1 from northwestern Puerto Rico [Avila et al 2002, Brantly et al 2000], but also occurs in other individuals with HPS1 [Brantly et al 2000, Hermos et al 2002] or HPS4 [Anderson et al 2003, Bachli et al 2004]. To date, convincing evidence of pulmonary fibrosis has not been reported for HPS3, HPS5, or HPS6, although there is evidence of this complication in some persons with HPS2. The fibrosis consists of progressive, restrictive lung disease with an extremely variable time course [Gahl et al 1998, Brantly et al 2000, Gahl et al 2002].

Colitis. A bleeding granulomatous colitis resembling Crohn's disease presents, on average, at age 15 years, with wide variability [Gahl et al 1998]. The colitis is severe in 15% of cases and occasionally requires colectomy; affected individuals may have the inflammatory bowel disease of HPS without the explicit diagnosis of colitis. Objective signs of colitis have been found primarily in persons with HPS1 or HPS4 [Hussain et al 2006]. Although the colon is primarily involved in HPS, any part of the alimentary tract, including the gingiva, can be affected.

Other. Cardiomyopathy and renal failure have also been reported in HPS [Witkop et al 1989].

Neutropenia and/or immune defects have been associated with HPS2 [Shotelersuk et al 2000, Huizing & Gahl 2002, Clark et al 2003, Fontana et al 2006].

Pathogenesis. Pulmonary fibrosis, granulomatous colitis, cardiomyopathy, and renal failure have been attributed to the lysosomal accumulation of ceroid lipofuscin, but this relationship is speculative.

Genotype-Phenotype Correlations

Correlations between specific HPS-causing mutations and particular clinical presentations are not convincing.

The pulmonary fibrosis of HPS is associated with Puerto Ricans homozygous for the c.1470_1486dup16 mutation in HPS1 [Gahl et al 1998]. However, the occurrence of lethal pulmonary fibrosis in an Irish individual with HPS1 mutations [Brantly et al 2000] and in Sri Lankan [Bachli et al 2004] and Eastern European [Anderson et al 2003] individuals with HPS4 mutations suggests that any HPS1 or HPS4 mutation can cause pulmonary disease. Pulmonary fibrosis did not occur in one study of four individuals with HPS5 [Huizing et al 2007].

Two brothers and a six-year-old boy with compound heterozygosity for AP3B1 mutations had typical HPS but also persistent neutropenia and an increased frequency of infections in childhood [Shotelersuk et al 2000, Huizing & Gahl 2002]. No clinical information is available on a fourth individual with AP3B1 mutations [Clark et al 2003]. A two-year-old boy diagnosed with HPS2 had fatal hemophagocytic lymphohistiocytosis [Enders et al 2006], and two Italian siblings had an immune defect involving abnormal natural killer cell function [Fontana et al 2006]. Two Turkish siblings with HPS2 manifested developmental delay and dysmorphic features, but consanguinity was also involved [Jung et al 2006].

Individuals with HPS3 mutations have milder symptoms than those with HPS1 mutations [Huizing et al 2001a]. The albinism in HPS3 is characterized by such minimal hypopigmentation that some individuals have carried the diagnosis of ocular albinism rather than oculocutaneous albinism. Visual acuity often approximates 20/100 or better. Bleeding is also mild and pulmonary involvement has not been observed. Significant granulomatous colitis occurs primarily in HPS1 and HPS4 [Hussain et al 2006]. The severity of clinical symptoms does not appear to correlate with the severity of the molecular defect.

The variability and severity of oculocutaneous albinism and bleeding diathesis found in HPS4 are similar to those of HPS1 [Suzuki et al 2002, Anderson et al 2003]. Pulmonary fibrosis and granulomatous colitis also occur in HPS4; no correlation has been found between the severity of symptoms and specific mutations.

HPS5 and HPS6 appear to resemble HPS3 in their mildness and lack of pulmonary disease. It is difficult to discern the severity of HPS7 and HPS8 based on the single case reported for each.

Nomenclature

HPS may have been referred to as non-neuronal ceroid-lipofuscinosis to differentiate it from neuronal ceroid-lipofuscinosis or Batten disease. In HPS, the nervous system appears to be spared.

Individuals with HPS with mild hypopigmentation but a bleeding disorder could be referred to as having "delta storage pool deficiency"; however, individuals with isolated delta storage pool deficiency do not have vision defects.

Prevalence

HPS occurs worldwide and has an estimated prevalence of 1:500,000 to 1:1,000,000 in non-Puerto Rican populations.

Prevalence of HPS1 in northwestern Puerto Rico is 1:1800. HPS1 has been reported in a small isolate in a Swiss village and as a genetic isolate in Japan [Ito et al 2005].

HPS3 occurs as a genetic isolate in central Puerto Rico [Anikster et al 2001, Santiago Borrero et al 2006].

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with Hermansky-Pudlak syndrome (HPS), the following are recommended:

• Complete ophthalmologic evaluation

• Skin examination for severity of hypopigmentation and, after infancy, for evidence of skin damage and skin cancer

• History of bleeding problems and symptoms suggesting pulmonary fibrosis and/or colitis. For evaluation for lung fibrosis, pulmonary function tests (PFTs) should be performed in individuals older than age 20 years.

Treatment of Manifestations

Eyes

• The majority of individuals with albinism have significant hyperopia (far-sightedness) or myopia (near-sightedness), and astigmatism. Correction of these refractive errors can improve visual acuity.

• Strabismus surgery is usually not required but can be performed for cosmetic purposes, particularly if the strabismus is marked or fixed. The surgery is not always successful.

• Aids such as hand-held magnifying devices or bioptic lenses are helpful adjuncts in the care of visually impaired individuals with HPS.

• Preferential seating in school is beneficial, and a vision consultant may be useful.

Skin. Treatment of skin cancer does not differ from that in the general population.

Bleeding

• Humidifiers may reduce the frequency of nosebleeds; oral contraceptives can limit the duration of menstrual periods. A levonorgestrel-releasing intrauterine system has been used with benefit for control of menorrhagia in a woman with HPS [Kingman et al 2004].

• Treatment of minor cuts includes placing thrombin-soaked gelfoam over an open wound that fails to clot spontaneously.

• For more invasive trauma, such as wisdom tooth extraction, DDAVP (1-desamino-8-D-arginine vasopressin, 0.2 µg/kg in 50 mL of normal saline) can be given as a 30-minute intravenous infusion just prior to the procedure. The use of DDAVP may or may not improve the bleeding time [Cordova et al 2005]. For extensive surgeries or protracted bleeding, platelet or red blood cell transfusions may be required.

Pulmonary fibrosis

• When the pulmonary disease becomes severe, oxygen therapy can be palliative.

• One individual with HPS1 remains well after undergoing lung transplantation [Lederer et al 2005]. The authors know of two additional, presumably successful, lung transplantations [Author, communication].

Colitis. The granulomatous colitis of HPS resembles Crohn's colitis and, as such, may respond to steroids and other anti-inflammatory agents. Remicade^® has also been used with benefit [Erzin et al 2006].

Prevention of Secondary Complications

Skin. Skin care in HPS is dictated by the amount of pigment in the skin and the cutaneous response to sunlight. Protection from the sun should be provided to prevent burning, other skin damage, and skin cancer. In very sensitive individuals, sun exposure as short as five to ten minutes can be significant, while exposure of 30 minutes or more is usually significant in less sensitive individuals. Prolonged periods in the sun require skin protection with clothing (hats with brims, long sleeves and pants, and socks). For extremely sun-sensitive individuals, sun screens with a high SPF value (total blocks with SPF 45-50+) are appropriate; for less sun-sensitive individuals, sun screens with SPF values of 15 or above can be used.

Bleeding. Individuals with HPS should consider obtaining a medical alert bracelet that explicitly describes the functional platelet defect, as the standard tests for bleeding dysfunction (platelet count, prothrombin time, partial thromboplastin time) are normal in HPS.

Pulmonary fibrosis. Prior to the development of pulmonary fibrosis, attention should be paid to maximizing pulmonary function. This entails avoidance of cigarette smoke, prompt treatment of pulmonary infections, immunization with influenza and pneumococcal vaccines, and regular moderate exercise.

Surveillance

Eyes. Annual ophthalmologic examination, including assessment of refractive error, is indicated.

Skin. Over many years, exposure to the sun of lightly pigmented skin can result in coarse, rough, thickened skin (pachydermia), solar keratoses (premalignant lesions), and skin cancer. Both basal cell carcinoma and squamous cell carcinoma can develop. Although skin melanocytes are present in individuals with HPS, melanoma is rare. Examination for these findings should be performed at least annually.

Pulmonary fibrosis. Pulmonary function testing should be performed annually in adults.

Colitis. Colitis is suspected in those with a history of cramping, increased mucus in the stool, and rectal bleeding; colonoscopy is used to confirm the diagnosis.

Agents/Circumstances to Avoid

Bleeding. All aspirin-containing products as well as activities that could involve the risk of a bleeding episode should be avoided.

Pulmonary fibrosis. Cigarette smoking decreases pulmonary function and may worsen progression of pulmonary fibrosis.

Testing of Relatives at Risk

In families with HPS3, HPS5, or HPS6, the evaluation of apparently unaffected siblings may yield a positive diagnosis.

In individuals with HPS1 and HPS4, the diagnosis of HPS will be apparent because the hypopigmentation and nystagmus are clinically evident.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Initial studies suggest a salutary effect on pulmonary function of the investigational drug pirfenidone in affected individuals with pulmonary function greater than 50% of normal [Gahl et al 2002]. A follow-up clinical trial was unable to confirm this finding, but also did not refute it [unpublished data].

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.

Other

In general, opaque contact lenses or darkly tinted lenses do not improve visual function. Dark glasses may be helpful for individuals with albinism, but many prefer to go without dark glasses because they reduce vision.

No successful therapy for or prophylaxis against the pulmonary fibrosis of HPS exists. Steroids are often tried but have no apparent beneficial effect.

Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.

See Consumer Resources for disease-specific and/or umbrella support organizations for this disorder. These organizations have been established for individuals and families to provide information, support, and contact with other affected individuals.

Mode of Inheritance

All types of Hermansky-Pudlak syndrome (HPS) are inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

• The parents of an affected child are obligate heterozygotes and thus carry one mutant allele.

• Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

• At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being neither affected nor a carrier.

• Once an at-risk sib is known to be unaffected, the chance of his/her being a carrier is 2/3.

• Heterozygotes are asymptomatic.

Offspring of a proband

• The offspring of an individual with HPS are obligate heterozygotes (carriers) for a mutant allele causing HPS.

• Rarely, families with two-generation pseudodominance have been identified; these result from an affected individual having children with a reproductive partner who is heterozygous (i.e., a carrier) for a mutant allele in the same HPS-causing gene.

Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier.

Carrier Detection

Carrier testing for the c.1470_1486dup16 duplication in HPS1 and the g.339_4260del3904 deletion and c.1303+1G>A splice site mutation in HPS3 is available on a clinical basis. Carrier testing for sequence variants in other genes may be available on a clinical basis once the mutations have been identified in the family.

Related Genetic Counseling Issues

Family planning

• The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.

• It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. See for a list of laboratories offering DNA banking.

Prenatal Testing

Prenatal diagnosis for pregnancies at 25% risk of inheriting some of the disease-causing mutations is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at approximately 15 to 18 weeks' gestation or chorionic villus sampling (CVS) at approximately ten to 12 weeks' gestation.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

No laboratories offering molecular genetic testing for prenatal diagnosis of some mutations that cause HPS are listed in the GeneTests Laboratory Directory. However, prenatal testing may be available for families in which the disease-causing mutations have been identified. For laboratories offering custom prenatal testing, see .

Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutations have been identified. For laboratories offering custom prenatal testing, see .

Literature Cited

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16. Erzin Y, Cosgun S, Dobrucali A, Tasyurekli M, Erdamar S, Tuncer M. Complicated granulomatous colitis in a patient with Hermansky-Pudlak syndrome, successfully treated with infliximab. Acta Gastroenterol Belg. 2006;69:213–6. [PubMed: 16929618]
17. Falcon-Perez JM, Starcevic M, Gautam R, Dell'Angelica EC. BLOC-1, a novel complex containing the pallidin and muted proteins involved in the biogenesis of melanosomes and platelet-dense granules. J Biol Chem. 2002;277:28191–9. [PubMed: 12019270]
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Suggested Reading

1. Bonifacino JS. Insights into the biogenesis of lysosome-related organelles from the study of the Hermansky-Pudlak syndrome. Ann N Y Acad Sci. 2004;1038:103–14. [PubMed: 15838104]
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Author Notes

Dr. Gahl is a pediatrician, medical geneticist, and biochemical geneticist who performs clinical and basic research into rare diseases. He has seen more than 250 patients with HPS and published more than 60 original articles and reviews on the subject in the past nine years.

Acknowledgments

The author appreciates the abiding contributions of Dr. Marjan Huizing to the compilation of data presented in this work.

Revision History

• 8 July 2010 (cd) Revision: sequence analysis available clinically for mutations in AP3B1 (HPS2), HPS5, HPS6, and BLOC1S3 (HPS8)

• 4 May 2010 (me) Comprehensive update posted live

• 27 November 2007 (cd) Revision: sequence analysis available clinically for HPS1 and HPS4; prenatal diagnosis available for HPS4.

• 21 March 2007 (me) Comprehensive update posted to live Web site

• 20 December 2004 (me) Comprehensive update posted to live Web site

• 2 January 2003 (tk) Comprehensive update posted to live Web site

• 24 July 2000 (me) Review posted to live Web site

• 27 January 2000 (wg) Original submission