The International Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry (NCT01374360) was initiated to optimize patient management by collecting data regarding disease burden, progression, and clinical outcomes. Herein, we report updated baseline demographics, clinical characteristics, disease burden data, and observed trends regarding clone size in the largest cohort of Registry patients. Patients with available data as of July 2017 were stratified by glycosylphosphatidylinositol (GPI)-deficient granulocyte clone size (< 10%, ≥ 10%-< 50%, and ≥ 50%). All patients were untreated with eculizumab at baseline, defined as date of eculizumab initiation or date of Registry enrollment (if never treated with eculizumab). Outcomes assessed in the current analysis included proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVEs; including thrombotic events [TEs]), bone marrow failure (BMF), red blood cell (RBC) transfusions, and PNH-related symptoms. A total of 4439 patients were included, of whom 2701 (60.8%) had available GPI-deficient granulocyte clone size data. Among these, median clone size was 31.8% (1002 had < 10%; 526 had ≥ 10%-< 50%; 1173 had ≥ 50%). There were high proportions of patients with HDA (51.6%), history of MAVEs (18.8%), BMF (62.6%), RBC transfusion (61.3%), and impaired renal function (42.8%). All measures except RBC transfusion history significantly correlated with GPI-deficient granulocyte clone size. A large proportion of patients with GPI-deficient granulocyte clone size < 10% had hemolysis (9.7%), MAVEs (10.2%), HDA (9.1%), and/or PNH-related symptoms. Although larger GPI-deficient granulocyte clone sizes were associated with higher disease burden, a substantial proportion of patients with smaller clone sizes had history of MAVEs/TEs.

Diagnostic delays in Pompe disease are common. The diagnostic gap (the time from the onset of symptoms to the diagnosis of Pompe disease) and factors associated with diagnostic delays were examined among Pompe Registry patients in three onset categories: Group A, onset ≤12 months of age with cardiomyopathy; Group B, onset ≤12 months without cardiomyopathy and onset >12 months to ≤12 years; and Group C, onset >12 years. Of 1,003 patients, 647 were available for analysis. In all groups, musculoskeletal signs and symptoms were among the most frequent presenting signs and symptoms, in addition to cardiomyopathy in Group A, which was part of the group's definition. Diagnostic gaps existed in all three groups. Patients presenting with respiratory and musculoskeletal signs and symptoms concurrently had the shortest diagnostic gap, while those presenting with neither respiratory nor musculoskeletal signs and symptoms had the longest. Independent factors influencing the probability of a long diagnostic gap included presenting signs and symptoms (all three groups) and year of diagnosis and age at symptom onset (Groups B and C). Group B, which represents the infantile patients without cardiomyopathy and juvenile Pompe cases, had the longest median gap (12.6 years). Diagnostic testing methods used also were reviewed. Despite the availability of blood-based assays that can be used to quickly and accurately diagnose Pompe disease, diagnostic gaps in Pompe patients across the disease spectrum continue.

Background: Paroxysmal nocturnal haemoglobinuria (PNH) is a rare disease. Although

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