Hermansky-Pudlak Syndrome Clinical Presentation

Updated: Jul 28, 2020
  • Author: Ahmed Farghaly Abdelhameed Omar, MD, PhD; Chief Editor: Hampton Roy, Sr, MD  more...
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Past ocular history in patients with Hermansky-Pudlak syndrome (HPS) should include the following:

  • Photophobia

  • Previous eyeglasses, bifocals, eyeglasses tints, low vision aids

  • Amblyopia therapy

  • Involuntary eye movements (nystagmus)

  • Eye deviations and

  • Strabismus surgery

Past systemic history in patients with Hermansky-Pudlak syndrome should include the following:

  • Bleeding diathesis: The most important questions when evaluating a patient with oculocutaneous albinism (OCA) are as follows: Do you bruise easily? Does your child bruise easily? Ask about aspirin and its derivatives intake.

  • The review of systems should include pulmonary symptoms associated to pulmonary fibrosis, such as dyspnea upon exertion, a history of previous pulmonary function tests, and steroid therapy.

  • Evaluate symptoms associated with colitis, such as abdominal pain, diarrhea, upper and lower gastrointestinal bleeding, and previous intestinal surgery.

  • Female patients with the syndrome should be asked about menometrorrhagia, abnormal uterine bleeding, complications during labor, cesarean delivery, and/or gynecologic surgery.

  • A history of sun exposure, sunblock application, skin biopsies, and malignancies should be obtained.

The family history of patients with Hermansky-Pudlak syndrome should include the following: nationality, parental consanguinity, and incidence of HPS in other family members.



A wide ocular phenotypic variety exists in patients with Hermansky-Pudlak syndrome. Ocular findings in these patients include the following: [10, 11, 12]

  • Poor visual acuity: Best-corrected visual acuity in patients with Hermansky-Pudlak syndrome ranges from 20/50 to 20/400 in the Snellen chart.

  • Refractive errors that range from high myopia to hyperopia may be present. With the rule astigmatism is most common in patients with the syndrome.

  • Strabismus: Patients with both horizontal and vertical eye deviations have been reported. The most common types of strabismus found in patients with the syndrome are esotropia and exotropia.

  • Patients with Hermansky-Pudlak syndrome have congenital nystagmus. Periodic alternating nystagmus is most prevalent in patients with the syndrome. A variety of amplitudes and frequencies have beenreported.

  • Patients with Hermansky-Pudlak syndrome have several anterior segment abnormalities, including prominent Schwalbe line, iris transillumination, and presenile cataracts. Iris transillumination varies from almost total transillumination (pigment found at the collarette) to minimal peripheral transillumination (mostly in patients with HPS type 3).

  • Patients with Hermansky-Pudlak syndrome have foveal hypoplasia. Macular transparency (grading of choroidal vessels visibility) ranges from transparent to opaque. All patients have albinotic mid periphery. Vascular architecture varies.

  • Previous studies report that patients with Hermansky-Pudlak syndrome have poor binocular vision.

  • Studies show that approximately 50% of patients with Hermansky-Pudlak syndrome have color vision defects upon HRR pseudoisochromatic plates testing.

  • Visual-evoked potentials show excessive decussation of optic nerve fibers.

  • Optical coherence tomography in patients with albinism shows that patients with OCA (all types included) have thicker foveas than the general population. This may be due to absence of a foveal pit as part of foveal hypoplasia in patients with OCA. Conversely, patients with OCA have lower macular volumes than the general population. This finding is compatible with loss of retinal nuclear layers in patients with OCA.

Patients with Hermansky-Pudlak syndrome have a wide variety of phenotypic skin findings.

  • Hair color varies from light blonde to dark brown. Hair and skin pigmentation is darker in patients with HPS type 3. The latter have brown hair and iris color.

  • Skin freckles, lentigines, actinic keratosis, and premalignant and malignant skin lesions may also be present in sun exposed areas.

Patients with Hermansky-Pudlak syndrome have several systemic findings: [13, 14, 15, 16]

  • Enamel hypoplasia

  • Since patients with Hermansky-Pudlak syndrome have bleeding tendencies, inspect lower extremities for ecchymosis.

  • Patients should have a pneumologic evaluation, since more than 50% of patients with Hermansky-Pudlak syndrome have pulmonary fibrosis. Auscultate patients for wheezing.



HPS is a group of autosomal recessive disorders. Therefore, consanguinity and geographical isolation increases the risk of affected offspring. Pseudodominance has been reported in the northwestern quarter of Puerto Rico, because of patients with the syndrome who marry carriers of the HPS genes in geographically isolated regions.

HPS results from a mutation in 1 of 10 genes that encode components in one of four complexes. [8] Fukai and coworkers identified an HPS gene, located in chromosome region 10q23.1-23.3 by using a positional cloning approach. [17] Genetic analysis of Puerto Rican patients identified a 16-base pair duplication/frameshift within exon 15. This results in a frameshift at codon Pro 496. This gene is called the HPS-1 gene.

Puerto Rican patients with HPS type 3 have all been homozygous for a 3,904-bp deletion in the HPS-3 gene, as described by Anikster and coworkers. [18]

However, further studies have shown evidence for locus heterogeneity in Puerto Ricans with the syndrome. Bailin and coworkers suggest that mutations in the adaptor-related code complex (termed AP-3) subunits may lead to some forms of HPS. [19] The AP-3 complex facilitates transport of vesicles from the trans-Golgi network and endosomal compartments. AP-3 interacts with tyrosine signals on proteins of lysosomes and other intracellular organelles.



Systemic complications in HPS are associated with accumulation of a ceroid-like substance in lysosomes of various tissues. Ceroid deposition in patients with HPS has been associated with pulmonary fibrosis, granulomatous enteropathic disease, and renal failure. Accumulation in the heart and kidneys is less common. This lysosomal defect has been reported in reticuloendothelial cells, bone marrow, and lung macrophages.