Bleeding assessment in female patients with the Hermansky-Pudlak syndrome-A case series.

INTRODUCTION: The Hermansky-Pudlak syndrome (HPS) is an autosomal recessive rare disorder characterized by oculocutaneous albinism, bleeding diathesis, chronic granulomatous colitis and/or pulmonary fibrosis. HPS is the most common single-gene disorder in Puerto Rico with a prevalence of 1:1,800 in the Northwest of the island. Risk of menorrhagia and post-partum hemorrhage (PPH) in cases of women with HPS have been described in the medical literature, but data regarding comprehensive description of bleeding diathesis remains lacking. For this reason, we aim to identify bleeding events using the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT), a standardized quantitative tool that translates the range of severity of bleeding symptoms into a cumulative bleeding score (BS). OBJECTIVE: To use the ISTH-BAT in HPS in order to describe bleeding symptoms and allow for comparison with other inherited bleeding disorders. METHODS: Puerto Rican females and adult participants with HPS based on genetic linkage were enrolled. The ISTH-BAT was administered and results were identified using descriptive statistical analysis. RESULTS: Questionnaire answers of twelve women with HPS-1 and HPS-3 were evaluated. Participants' mean BS was HPS-1 (11.4) and HPS-3 (8.0) Participants with HPS-1 and HPS-3 reported abnormal bleeding events that presented during dental extractions, menorrhagia, surgical interventions, gastrointestinal, oral cavity and post-partum. Patients with history of pulmonary fibrosis (PF) showed a higher mean bleeding score than those who had no history of PF. CONCLUSIONS: Female patients with HPS type 1 and 3 experienced abnormal bleeding events according to the ISTH-BAT bleeding score. Bleeding medications were inconsistently used and varied independently from healthcare professionals. The benefits of this study were to understand the history of bleeding complications in patients with HPS type 1 and 3 using an international validated system. The results of this study will help design strategies to improve the care we provide to this population.

Hermansky-Pudlak syndrome with a novel genetic variant in HPS1 and subsequent accelerated pulmonary fibrosis: significance for phenocopy diseases.

The Hermansky-Pudlak syndrome (HPS) is a collection of autosomal-recessive disorders characterised by tyrosinase-positive oculocutaneous albinism (OCA), bleeding diatheses and, in selected individuals, early-onset accelerated pulmonary fibrosis, neutropaenia and granulomatous colitis. We describe a young man who presented following a self-directed literature review prompted by severe bleeding complications following minor surgical and dental procedures in the context of OCA. HPS was clinically suspected, with subsequent genetic testing confirming biallelic mutations in the HPS1 gene. Of interest, this is the only described HPS type 1 patient with two different (compound heterozygote) splice site variants in HPS1 In addition to detailing a novel genetic result and outlining the progressive clinical course of disease in this case, we discuss the management of HPS, the prognostic value of subtype analysis and the technical difficulties relating to transplantation in the case of HPS-associated advanced pulmonary fibrosis. This case also illustrates the concept of lung phenocopy relationships and the potential for elucidating the pathogenesis of more common pulmonary disorders by studying genetic diseases that result in similar phenotypes. Furthermore, it re-emphasises the importance of the patient voice, particularly with regard to complex diagnoses and rare diseases.

Compound heterozygous mutations in 2 siblings with Hermansky-Pudlak syndrome type 1 (HPS1).

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder causing oculocutaneous albinism, bleeding disorder and ceroid lipofuscinosis. Platelets from HPS patients are characterized by the absence of dense (delta)-bodies. There are eight known human HPS GENES (HPS1-HPS8), each leading to a particular clinical HPS subtype. Restrictive lung disease, granulomatous colitis and cardiomyopathy have been described in HPS1 patients. PATIENTS: We identified HPS1 in Russian and in German siblings. All four patients show a typical HPS phenotype. The two older Russian patients demonstrate excessive bleeding after tooth extractions, recurrent epistaxis and hematomas. The two younger German patients suffer only from hematomas, so far. METHODS/RESULTS: Patients' platelets showed severe pathological agglutination/aggregation. Flow cytometry analysis demonstrated absence of platelet delta-granule secretion. Three different mutations in the HPS1 gene were found in the two families. Two mutations, p.H119delC and p.Q397delC identified in the Russian siblings had been previously described. The German siblings presented with a novel frameshift mutation (p.Q32_S33delCAGT) and the known p.Q397delC mutation. CONCLUSION: Patients with oculocutaneous albinism should be investigated for increased clinical bleeding symptoms. In case of increased bleeding symptoms, analyses of primary hemostasis should be initiated to confirm HPS. Molecular genetic investigations should be performed to distinguish the different subtypes of HPS which is important for therapy and prognosis.

Hermansky-Pudlak syndrome: dental management considerations.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism (OCA), platelet dysfunction, and ceroid storage. It is common among the Puerto Rican population and is expected to spread within the United States and other countries. Due to the platelet deficiency, these patients are of major concern to pediatric dentists. The purpose of this article is to explain in detail the characteristic triad of this syndrome and to propose an adequate approach to perform dental treatment, using appropriate protection recommendations for HPS patients. Recommendations for dental treatment are considered. They include the use of: (1) eyeglasses with 99 UV filter to protect them from the unpleasant dental light stimulus; (2) an extra-soft toothbrush and conservative brushing technique; (3) medication with antifibrinolitic agents; and (4) local measures to achieve hemostasis.