RESUMO
Hermansky-Pudlak syndrome (HPS) is a multisystemic autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis, and lethal pulmonary fibrosis (PF) in some HPS subtypes. During middle adulthood, ground-glass opacities, reticulation, and traction bronchiectasis develop with progression of PF. HPS is an orphan disease occurring in 1 in 500,000 to 1,000,000 individuals worldwide, though the prevalence is 1 in 1,800 in individuals with Puerto Rican heritage. Recessive mutations or disruptions in HPS genes alter the function of HPS proteins which are components of biogenesis of lysosome-related organelle complexes and are critical for intracellular protein trafficking. Diagnosis and management of HPS-related comorbidities represent a challenge to physicians, and a multidisciplinary clinical approach is necessary for early detection, health management, and surveillance of PF in patients with HPS types 1, 2, and 4. Treatment options for individuals with HPS-PF include pirfenidone and lung transplantation. In this article, we describe the epidemiology, genetics, clinical manifestations, and management of HPS.
Assuntos
Síndrome de Hermanski-Pudlak/diagnóstico , Síndrome de Hermanski-Pudlak/terapia , Progressão da Doença , Síndrome de Hermanski-Pudlak/epidemiologia , Síndrome de Hermanski-Pudlak/genética , Humanos , Mutação , Porto Rico/etnologia , Fibrose Pulmonar/epidemiologia , Fibrose Pulmonar/etiologiaRESUMO
Hermansky-Pudlak Syndrome is a rare form of albinism, affecting approximately one in 500,000 to one in 1,000,000 non-Hispanic individuals. The syndrome is more commonly found in Hispanics, where one in 18,00 individuals in Northwestern Puerto Rico are impacted. Because of the rarity of this chronic condition, patients often face challenges in their ability to cope with the diagnosis. A phenomenological study was conducted to explore the experience of individuals with this rare genetic disease. A purposive sample of adults between the ages of 20 and 49 diagnosed with Hermansky-Pudlak Syndrome was interviewed (N = 23). The majority (83%) were female. Data analysis resulted in the emergence of themes related to long road to diagnosis, learning to move forward, burden of being the expert, and survival through belonging to the HPS community.
Assuntos
Síndrome de Hermanski-Pudlak/psicologia , Qualidade de Vida/psicologia , Doenças Raras/psicologia , Adulto , Feminino , Síndrome de Hermanski-Pudlak/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Porto Rico/epidemiologia , Adulto JovemRESUMO
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease that displays genetic heterogeneity; there are 9 known subtypes. HPS is characterized by oculocutaneous albinism, a platelet storage pool deficiency and resultant bleeding diathesis, and lysosomal accumulation of ceroid lipofuscin. Patients with HPS, specifically those with the genotypes HPS-1, HPS-2, or HPS-4, are predisposed to interstitial lung disease. In addition, some patients with HPS develop granulomatous colitis. Optimal health care requires a thorough knowledge of the unique health risks and functional limitations associated with this syndrome.
Assuntos
Síndrome de Hermanski-Pudlak/terapia , Assistência de Longa Duração/métodos , Albinismo Oculocutâneo/diagnóstico , Albinismo Oculocutâneo/epidemiologia , Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/terapia , Criança , Aberrações Cromossômicas , Comportamento Cooperativo , Comparação Transcultural , Estudos Transversais , Análise Mutacional de DNA , Avaliação da Deficiência , Diagnóstico Precoce , Genes Recessivos , Genótipo , Síndrome de Hermanski-Pudlak/diagnóstico , Síndrome de Hermanski-Pudlak/epidemiologia , Síndrome de Hermanski-Pudlak/genética , Humanos , Comunicação Interdisciplinar , Fenótipo , Deficiência do Pool Plaquetário/diagnóstico , Deficiência do Pool Plaquetário/epidemiologia , Deficiência do Pool Plaquetário/genética , Deficiência do Pool Plaquetário/terapia , Porto RicoRESUMO
BACKGROUND: Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by albinism, mucocutaneous bleeding, and storage of ceroid material in macrophages. Patients who are not easily identified by physical characteristics (mostly HPS-3 patients) may have hemorrhagic complications with trauma or surgery. OBJECTIVE: To determine the prevalence of HPS-3 in Puerto Rican newborns using DNA pooling technique. DESIGN/METHODS: Twelve percent of annual Puerto Rican births were tested randomly by polymerase chain reaction for the HPS-3 mutation, using pooled DNA extracted from dried blood samples. RESULTS: HPS-3 mutation was detected in 75 samples. Two newborns were found to be homozygous. Carrier frequency was 1:85 (1.18%). CONCLUSIONS: The HPS-3 carrier frequency found (1.18%) justifies universal newborn screening in Puerto Rico. DNA pooling reduces time and labor in newborn screening thus facilitating early diagnosis and treatment of children with HPS-3 and the provision of genetic counseling to parents and relatives.
Assuntos
Síndrome de Hermanski-Pudlak/epidemiologia , Síndrome de Hermanski-Pudlak/genética , Triagem Neonatal , Frequência do Gene , Testes Genéticos , Heterozigoto , Humanos , Recém-Nascido , Reação em Cadeia da Polimerase , Prevalência , Porto Rico/epidemiologiaRESUMO
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a storage pool deficiency due to an absence of platelet dense bodies. Lysosomal ceroid lipofuscinosis, pulmonary fibrosis and granulomatous colitis are occasional manifestations of the disease. HPS occurs with a frequency of one in 1800 in north-west Puerto Rico due to a founder effect. Several non-Puerto Rican patients also have mutations in HPS1, which produces a protein of unknown function. Another gene, ADTB3A, causes HPS in the pearl mouse and in two brothers with HPS-2 (refs. 11,12). ADTB3A encodes a coat protein involved in vesicle formation, implicating HPS as a disorder of membrane trafficking. We sought to identify other HPS-causing genes. Using homozygosity mapping on pooled DNA of 6 families from central Puerto Rico, we localized a new HPS susceptibility gene to a 1.6-cM interval on chromosome 3q24. The gene, HPS3, has 17 exons, and a putative 113.7-kD product expected to reveal how new vesicles form in specialized cells. The homozygous, disease-causing mutation is a large deletion and represents the second example of a founder mutation causing HPS on the small island of Puerto Rico. We also present an allele-specific assay for diagnosing individuals heterozygous or homozygous for this mutation.
Assuntos
Proteínas de Transporte/genética , Cromossomos Humanos Par 3/genética , Síndrome de Hermanski-Pudlak/genética , Alelos , Sequência de Aminoácidos , Northern Blotting , Análise Mutacional de DNA , Feminino , Efeito Fundador , Triagem de Portadores Genéticos , Predisposição Genética para Doença , Genótipo , Síndrome de Hermanski-Pudlak/epidemiologia , Homozigoto , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Dados de Sequência Molecular , Mutação , Especificidade de Órgãos , Linhagem , Fenótipo , Mapeamento Físico do Cromossomo , Porto Rico/epidemiologia , Deleção de SequênciaRESUMO
Defects in a triad of organelles (melanosomes, platelet granules, and lysosomes) result in albinism, prolonged bleeding, and lysosome abnormalities in Hermansky-Pudlak syndrome (HPS). Defects in HPS1, a protein of unknown function, and in components of the AP-3 complex cause some, but not all, cases of HPS in humans. There have been 15 inherited models of HPS described in the mouse, underscoring its marked genetic heterogeneity. Here we characterize a new spontaneous mutation in the mouse, cappuccino (cno), that maps to mouse chromosome 5 in a region conserved with human 4p15-p16. Melanosomes of cno/cno mice are immature and dramatically decreased in number in the eye and skin, resulting in severe oculocutaneous albinism. Platelet dense body contents (adenosine triphosphate, serotonin) are markedly deficient, leading to defective aggregation and prolonged bleeding. Lysosomal enzyme concentrations are significantly elevated in the kidney and liver. Genetic, immunofluorescence microscopy, and lysosomal protein trafficking studies indicate that the AP-3 complex is intact in cno/cno mice. It was concluded that the cappuccino gene encodes a product involved in an AP-3-independent mechanism critical to the biogenesis of lysosome-related organelles. (Blood. 2000;96:4227-4235)