ABSTRACT
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.
Subject(s)
Hermanski-Pudlak Syndrome/diagnosis , Hermanski-Pudlak Syndrome/therapy , Disease Progression , Hermanski-Pudlak Syndrome/epidemiology , Hermanski-Pudlak Syndrome/genetics , Humans , Mutation , Puerto Rico/ethnology , Pulmonary Fibrosis/epidemiology , Pulmonary Fibrosis/etiologyABSTRACT
OBJECTIVE: To assess contributing factors to increased obesity risk, by comparing children with autism spectrum disorder (ASD), developmental delays/disorders, and general population controls in weight status, and to examine associations between weight status and presence of co-occurring medical, behavioral, developmental, or psychiatric conditions across groups and ASD severity among children with ASD. STUDY DESIGN: The Study to Explore Early Development is a multisite cross-sectional study of children, 2-5 years of age, classified as children with ASD (n = 668), children with developmental delays/disorders (n = 914), or general population controls (n = 884). Using an observational cohort design, we compared the 3 groups. Children's heights and weights were measured during a clinical visit. Co-occurring conditions (medical, behavioral, developmental/psychiatric) were derived from medical records, interviews, and questionnaires. ASD severity was measured by the Ohio State University Global Severity Scale for Autism. RESULTS: The odds of overweight/obesity were 1.57 times (95% CI 1.24-2.00) higher in children with ASD than general population controls and 1.38 times (95% CI 1.10-1.72) higher in children with developmental delays/disorders than general population controls. The aORs were elevated for children with ASD after controlling for child co-occurring conditions (ASD vs general population controls: aOR = 1.51; 95% CI 1.14-2.00). Among children with ASD, those with severe ASD symptoms were 1.7 times (95% CI 1.1-2.8) more likely to be classified as overweight/obese compared with children with mild ASD symptoms. CONCLUSIONS: Prevention of excess weight gain in children with ASD, especially those with severe symptoms, and in children with developmental delays/disorders represents an important target for intervention.
Subject(s)
Autism Spectrum Disorder/epidemiology , Body Weight , Child Development Disorders, Pervasive/epidemiology , Child Development , Population Surveillance/methods , Autism Spectrum Disorder/diagnosis , Child Development Disorders, Pervasive/diagnosis , Child, Preschool , Comorbidity , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Prevalence , Retrospective Studies , Severity of Illness Index , United States/epidemiologyABSTRACT
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive genetic disorder characterized by oculocutaneous albinism and a bleeding diathesis due to platelet dysfunction. More than 50% of cases worldwide are diagnosed on the Caribbean island of Puerto Rico. Genetic testing plays a growing role in diagnosis; however, not all patients with HPS have identified genetic mutations. In Puerto Rico, patients with HPS are often identified shortly after birth by their albinism, although the degree of hypopigmentation is highly variable. Ten subtypes have been described. Patients with HPS-1, HPS-2, and HPS-4 tend to develop pulmonary fibrosis in Puerto Rico; 100% of patients with HPS-1 develop HPS-PF. HPS-PF and idiopathic pulmonary fibrosis are considered similar entities (albeit with distinct causes) because both can show similar histological disease patterns. However, in contrast to idiopathic pulmonary fibrosis, HPS-PF manifests much earlier, often at 30-40 years of age. The progression of HPS-PF is characterized by the development of dyspnea and increasingly debilitating hypoxemia. No therapeutic interventions are currently approved by the U.S. Food and Drug Administration for the treatment of HPS and HPS-PF. However, the approval of two new antifibrotic drugs, pirfenidone and nintedanib, has prompted new interest in identifying drugs capable of reversing or halting the progression of HPS-PF. Thus, lung transplantation remains the only potentially life-prolonging treatment. At present, two clinical trials are recruiting patients with HPS-PF to identify biomarkers for disease progression. Advances in the diagnosis and management of these patients will require the establishment of multidisciplinary centers of excellence staffed by experts in this disease.