Table 2 Observational studies of ASMD clinical burden since 2004
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 |