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Table 2 Observational studies of ASMD clinical burden since 2004

From: Disease manifestations and burden of illness in patients with acid sphingomyelinase deficiency (ASMD)

Reference Study type Patients Objective/Evaluation Main findings
Lidove et al. 2016 [45] Retrospective NPD B (N = 28 adults) Clinical phenotype, laboratory tests High frequency of MGUS
Cassiman et al. 2016 [31] Retrospective NPD B/variant NPD B (N = 85) Cause of death, morbidity Overall leading causes of death were respiratory failure and liver failure
Acuña et al. 2015 [24] Retrospective NPD B: SMPD1 variant p.(Ala359Asp) Epidemiology, phenotype Moderate to severe NPD B with normal cognitive and psychomotor development
McGovern et al. 2013 [32] Prospective NPD B, N = 103; age 1–72 years Morbidity, survival, cause of death NPD B is a life-threatening disorder with morbidity and mortality, especially in children
Wasserstein et al. 2013 [33] Prospective NPD B, N = 46 (20 children, 26 adults) Skeletal manifestation (comparative analysis with healthy controls) Significant association between reduced bone marrow mineral density and increased splenomegaly
Zhang et al. 2013 [20] Retrospective ASMD, N = 27
(8 NPD A, 4 intermediate, 15 NPD B)
Genotype, phenotype Comparatively high incidence of NPD A in the Chinese population
Hollak et al. 2012 [4] Retrospective/ prospective ASMD, N = 25
(4 severe [NPD A], 6 intermediate, 15 attenuated [NPD B])
Clinical phenotype In NPD B patients, pulmonary disease is the most debilitating clinical feature
Thurberg et al. 2012 [34]a Phase 1 trial (rhASM), (baseline data) Adults (18–65 years) with ASMD, N = 17 Liver and skin pathology Liver fibrosis in almost all patients. Variable sphingomyelin accumulation; high sphingomyelin accumulation associated with liver enlargement
Henderson et al. 2009 [35] Prospective qualitative case study N = 17; 8 patients (16–43 years old) with NPD B, 9 parents Psychosocial burden of disease Limited physical activity and social isolation and peer rejection are major stressors, particularly for patients 10–16 years
McGovern et al. 2008 [36] Prospective cross-sectional survey NPD B, n = 59 Suitable endpoints for future clinical trials, (clinical assessments, imaging, QoL [CHQ-PF50, SF-36], laboratory tests) NPD B patients have multi-system involvement and clinical variable phenotypes. Almost all had splenomegaly, hepatomegaly and interstitial lung disease. Common symptoms: bleeding (49%), pulmonary infections (42%), shortness of breath (42%) and joint/limb pain (39%); low platelets, abnormal lipid values and liver function tests. Delayed growth in adolescence. Mild decrease in QoL with standard instruments
Guillemot et al. 2007 [37] Retrospective N = 13, 2–9 years old
1 NPD A, 10 NPD B, 2 other (NPD C)
Lung disease All patients had signs of interstitial lung disease, 1 patient died of respiratory failure, 5 required long-term oxygen therapy
Mihaylova et al. 2007 [6] Prospective Intermediate NPD, N = 20, 7 months to 35 years old Phenotype/genotype relationship Variable neural involvement in patients with intermediate NP and identical genetic background
McGovern et al. 2006 [3] Prospective longitudinal NPD A, 10 patients (3–6 months at study entry) NPD A natural history All infants had severely impaired cognitive and motor development, cherry-red spots; median survival from diagnosis was 21 months; cause of death was respiratory failure (9 patients) and complications from bleeding (1 patient)
Mendelson et al. 2006 [38] Prospective NPD B, N = 53 Pulmonary findings Interstitial lung disease was present in most patients; there was no quantitative correlation between imaging findings and lung function
Wasserstein et al. 2006 [8] Prospective NPD B/intermediate NPD, N = 64 Prevalence of neurologic disease 10/64 patients had mild hypotonia or hyporeflexia; 5/64 patients had significant progressive neurologic abnormalities including cognitive impairment
Pavlů-Pereira et al. 2005 [7] Retrospective ASMD, N = 25 (5 NPD A, 4 NPD B, 16 intermediate ASMD) Phenotype Description of an intermediate phenotype with overt, borderline or subclinical neurologic symptoms of neuronopathy
McGovern et al. J Pediatr 2004 [39] Prospective Children with ASMD, N = 40 (10 NPD A; 30 NPD B) Lipid abnormalities All children had lipid abnormalities including low HDL, high LDL and/or high TG
McGovern et al. Ophthalmology 2004 [40] Prospective NPD B, N = 45 (3–65 years) Ocular manifestations 15/45 patients had macular stigmata with no evidence of neurodegeneration
Wasserstein et al. 2004 [5] Prospective longitudinal NPD B, N = 29 (2–64 years at study entry) NPD B natural history The natural history of NPD B is characterized by hepatosplenomegaly with progressive hypersplenism, worsening atherogenic lipid profile, gradual deterioration in pulmonary function and stable liver dysfunction
  1. ASMD acid sphingomyelinase deficiency, CHQ-PF50 Child Health Questionnaire – Parental Form 50 for pediatric patients, HDL high-density lipoprotein, LDL low-density lipoprotein, MGUS monoclonal gammopathy of unknown significance, NPD Niemann-Pick disease, Qol quality of life, rhASM recombinant human ASM, SF-36 Short-Form 36, TG triglycerides
  2. aReports baseline observational data from a phase 1 clinical trial