Clinical Guidance

Correlations between specific HPS-causing variants in any one gene and particular clinical presentations are not convincing.

Source: GeneReviews — "Hermansky-Pudlak Syndrome"

Diagnostic Criteria

Suggestive Findings

Hermansky-Pudlak syndrome (HPS) should be suspected in a proband with the following clinical, laboratory, and family history findings.

Clinical findings

• Nystagmus, low vision, photophobia, strabismus

• Skin and hair color lighter than other family members

• Increased bruising, epistaxis, gingival bleeding, and prolonged bleeding after minor procedures (e.g., circumcision, tooth extraction)

Laboratory findings

• Platelet aggregation testing showing impaired secondary aggregation response

• Prothrombin time, partial thromboplastin time, and platelet counts typically normal

• Absence of platelet delta granules (dense bodies) on whole mount electron microscopy

Source: GeneReviews — "Hermansky-Pudlak Syndrome"

Differential Diagnosis

Albinism. The diagnosis of Hermansky-Pudlak syndrome (HPS) should be considered in anyone with oculocutaneous albinism or ocular albinism, as the bleeding diathesis can be mild, unrecognized, or previously disregarded. Pathogenic variants in HPS-related genes have been identified in next-generation sequencing studies of individuals with oculocutaneous albinism or ocular albinism . Some would advocate screening all individuals with albinism for HPS by examining their platelets for absent dense bodies. Genes known to be associated with albinism are summarized in .

Table 2a.

Differential Diagnosis of Hermansky-Pudlak Syndrome: Disorders with Albinism

Gene(s) | Disorder | MOI | Clinical Features

Source: GeneReviews — "Hermansky-Pudlak Syndrome"

Management Guidelines

Clinical practice guidelines for Hermansky-Pudlak syndrome (HPS) have not been published; however, clinicians with expertise in HPS care have published management recommendations . Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with HPS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Hermansky-Pudlak Syndrome

Source: GeneReviews — "Hermansky-Pudlak Syndrome"

Clinical Guidance

The following should be avoided:

• All nonsteroidal anti-inflammatory medications and aspirin-containing products

• Therapeutic anticoagulants (should be used only if medically indicated)

• High-impact sports and activities that could increase the risk of bleeding

• Tobacco products (which decrease pulmonary function and may exacerbate pulmonary fibrosis)

• Other pulmonary toxicants (e.g., inorganic and organic fibers, volatile chemicals, polluted environments)

• Direct sun exposure without protection (e.g., protective clothing, sunscreen, and UV-blocking sunglasses)

Source: GeneReviews — "Hermansky-Pudlak Syndrome"

Therapies Under Investigation

No medications are currently approved by the US Food and Drug Administration as treatment for HPS. Some medications for HPS-related pulmonary fibrosis have been investigated. Corticosteroid drugs were not effective and are not recommended for therapy . Clinical trials investigating pirfenidone, an oral antifibrotic drug approved as treatment for idiopathic pulmonary fibrosis (IPF), were inconclusive . Other antifibrotic therapies being studied as treatment for IPF, including tyrosine kinase inhibitors, are potential therapeutic candidates for HPS-related pulmonary fibrosis . Gene therapy and gene editing are potential future treatments for HPS . Preclinical studies of gene editing for HPS1 variant and gene replacement of HPS1 or AP3B1 are ongoing. Search ClinicalTrials.

Source: GeneReviews — "Hermansky-Pudlak Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 5. Recommended Surveillance for Individuals with Hermansky-Pudlak Syndrome

Source: GeneReviews — "Hermansky-Pudlak Syndrome"