Fibrosis pulmonar familiar en el síndrome de Hermansky-Pudlak

La fibrosis pulmonar familiar en el contexto del síndrome de Hermansky-Pudlak es una entidad nosológica poco frecuente y cuyo único enfoque terapéutico definitivo es el trasplante pulmonar en los estadios avanzados. Describimos algunos aspectos clínicos diagnósticos y terapéuticos que configuran el manejo de las enfermedades huérfanas en países como el nuestro.

Family pulmonary fibrosis in the context of Hermansky-Pudlak syndrome is a rare nosological entity whose only definitive therapeutic approach is lung transplantation in the advanced stages. We describe some diagnostic and therapeutic clinical aspects that shape the management of orphan diseases in countries like ours.

Genotypes and clinical phenotypes of Hermansky-Pudlak syndrome / 中华实验眼科杂志

Objective:To analyze the genotypes and clinical phenotypes of two families with Hermansky-Pudlak syndrome (HPS).Methods:The method of pedigree investigation was adopted.A Han Chinese HPS family and a Hui Chinese HPS family were enrolled in People's Hospital of Ningxia Hui Autonomous Region from June 2020 to May 2021.Clinical data of two probands and their phenotypically normal parents were collected.Relevant ocular and systemic examinations were carried out.Platelet dense granules in the two probands were observed with an electron microscope.DNA was extracted from peripheral venous blood collected from the subjects.The pathogenic genes were screened by whole exome sequencing.The potential disease-causing variations were analyzed by bioinformatics analysis.Validation and family cosegregation analysis of the pathogenic variations were performed by Sanger sequencing.The relationship between HPS-related gene variations and clinical characteristics was explored.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region (No.2016018).Written informed consent was obtained from each subject or custodian before any medical examination.Results:The two families were consistent with autosomal recessive inheritance pattern.In family 1 with a family history of consanguineous marriage, the proband had no obvious hypopigmentation on his facial skin, hair, eyebrows and eyelashes.Horizontal nystagmus, exotropia, mild visual impairment, iris atrophy, positive light transmission, orange fundus, pigment loss, macular hypoplasia, prolonged prothrombin time in laboratory examination, and a significant reduction of platelet dense granules by electron microscopy were observed.The proband in family 2 had pale brown hair and eyebrows, severe visual impairment, normal iris pigment, longer thrombin time in laboratory tests, and characteristics similar to those of the proband in family 1.A novel homozygous variant c. 2887G>T (p.E963X) was detected in the HPS3 gene of the proband in family 1.The parents of the proband from family 1 both carried a heterozygous variant c.2887G>T (p.E963X).Compound heterozygous variants were detected in HPS5 gene of the proband in family 2, c.2952-2A>C splicing variation and heterozygous deletion (a 3 144-bp deletion, located in chr11: 18302108-18305251, exon 22).The parents of the proband from family 2 carried a heterozygous variation.The three novel variations were labeled as pathogenic according to the ACMG standards and guidelines. Conclusions:Family 1 is with HPS-3 and family 2 is with HPS-5.There is a certain genotype-phenotype correspondence in the two types of HPS.

Hermansky Pudlak Syndrome Type 2:A Rare Case Report.

Hermansky-Pudlak Syndrome (HPS) is a rareautosomal recessive disorder characterized byOculocutaneous Albinism (OCA), platelet disorder,and ceroid accumulation. It is common in North WestPuerto Rico region, and the incidence reported is1/500000. It is a rare genetic disorder with plateletdysfunction resulting in bleeding diathesis. Here wereport one such rare case of HPS type 2 in a 7-year-oldboy with difficulty in chewing.

Síndrome de Hermansky-Pudlak: Expresión clínica variable en dos casos clínicos / Hermansky-Pudlak syndrome: variable clinical expression in two cases

Introducción. El síndrome de Hermansky-Pudlak es un padecimiento genético caracterizado por albinismo y hemorragias, en grado variable, por alteraciones en la estructura de las plaquetas. Puede presentar alteraciones pulmonares, intestinales o renales. En la literatura se han reportado varias alteraciones genéticas relacionadas a este síndrome. Casos clínicos. Se presentan dos casos. El primero se trató de un adolescente de sexo masculino con albinismo mucocutáneo y afección a nivel renal. Los episodios de sangrado iniciaron después de ser sometido a venopunciones y estudios invasivos. Desarrolló, incluso, un hematoma perirrenal. Después de una sepsis de foco abdominal, presentó hemoperitoneo y hemorragia pulmonar, que precipitó su muerte; el diagnóstico se realizó post mórtem. El segundo caso se trató de una paciente de sexo femenino en quien, desde el periodo de lactancia, se identificó el síndrome por el albinismo mucocutáneo, los episodios de sangrado y los datos de fibrosis pulmonar progresiva, lo que ha limitado su capacidad vital. Conclusiones. El diagnóstico del síndrome, así como el abordaje correcto y temprano pueden evitar el desarrollo de complicaciones o limitar su evolución. Aún es materia de debate si las alteraciones genéticas descritas se asocian a la expresión de alguna manifestación clínica particular.

Background. Hermansky-Pudlak syndrome is a genetic disorder characterized by albinism and bleeding of varying degrees due to alteration in the structure of the platelets. The disorder may be accompanied by pulmonary, intestinal or kidney involvement. Identification of several genetic alterations in this syndrome has been reported. Case reports. We present two cases: the first of an adolescent male with mucocutaneous albinism and renal involvement. Bleeding episodes started after being subjected to invasive studies and venipunctures, developing a perinephric hematoma. After severe sepsis, the patient developed hemoperitoneum and pulmonary hemorrhage, which precipitated the patient's death. Diagnosis was made postmortem. In the second case, a female patient was diagnosed during infancy due to albinism and bleeding episodes, with progressive pulmonary fibrosis that to date has limited her vital lung capacity. Conclusions. Early diagnosis of the syndrome as well as the correct approach may prevent the development of complications or limit the evolution. It is still under debate whether the genetic alterations described are associated with the expression of any particular clinical manifestation.

Albinism and lung fibrosis in a young man – the first case of adult Hermansky-Pudlak Syndrome reported in Malaysia

A young gentleman of Indian descent with oculacutaneous albinism (OCA) was found to have severe pulmonary fibrosis at first presentation. Following investigations, he was diagnosed with Hermansky-Pudlak Syndrome (HPS). It is a genetic condition characterised by albinism, bleeding diathesis and multisystem disorder observed in individuals of particular descents. Although there is no curative treatment apart from lung transplantation, preventive measures to minimise pulmonary insult may change the natural history of the disease. Therefore HPS should be actively sought, monitored and risk factors addressed in individuals with OCA and bleeding diathesis particularly those of Indian descent as they may develop serious complications such as pulmonary fibrosis in the future.