Clinical Guidance

Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and other organ involvement in specific subtypes . Signs and symptoms of oculocutaneous albinism in HPS are variable but visual acuity generally remains stable. Eyes. Nearly all children with HPS have nystagmus at birth, often noticed by the parents and the examining physician in infancy. Children with HPS may also have periodic alternating nystagmus, wandering eye movements, and lack of visual attention. The nystagmus can be very fast early in life and generally slows with time, but nearly all individuals have nystagmus throughout their lives. The development of pigment in the iris or retina does not affect the nystagmus.

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"

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"