Table 1.

Study design and major findings in ASMD natural history studies

Parameter	Current study		McGovern et al. (2006)		McGovern et al. (2008)		McGovern et al. (2013)		Wasserstein et al. (2004)		Hollak et al. (2012)
Patients	N = 100		N = 10		N = 59		N = 103		N = 29		N = 25
Phenotype; number of patients (n); median age at diagnosis
Infantile neurovisceral	n = 13	6 months	n = 10	6 months	0		0		0		n = 4	6 months
Chronic neurovisceral	n = 6	8.9 years	0		0		n = 8		0		n = 6	3 years
Chronic visceral	n = 81	9.3 years	0		n = 59	9.8 years	n = 95	8.1 years	n = 29	NA	n = 15	32 years
Type of study	Retrospective chart review		Case series		Prospective cross-sectional survey		Retrospective chart review		10-year longitudinal study		Retrospective chart review with prospective follow-up of chronic disease
Study centers	Brazil (n = 46), Canada (n = 13), United States (n = 41)		United States		Brazil (n = 13), France (n = 7), Germany (n = 5), Italy (n = 8), United States (n = 26)		United States		United States		The Netherlands and Belgium
Mortality	Infantile neurovisceral: ten deaths Chronic visceral: two deaths		Ten deaths (100%)				Chronic neurovisceral: 7 deaths Chronic visceral: 11 deaths		Three deaths		Infantile neurovisceral: four deaths Chronic ASMD: five deaths
Causes of death	Respiratory failure (n = 3), pneumonia (n = 3), lung disorder (n = 1), hepatic failure (n = 2), unknown (n = 3)		Respiratory failure (n = 9) and complications from bleeding (n = 1)				Pneumonia (n = 5), liver failure (n = 3), hemorrhage (n = 3), other (n = 7)		One each due to traumatic subdural hematoma, liver failure, failed bone marrow transplant complications		Pulmonary disease (n = 4), progressive neurological symptoms (n = 1), malignant edema with subdural hematoma (n = 1), malignancy (n = 1), unknown cause (n = 2)
Major morbidities	HS, GI disorders, respiratory disorders, infections		HS, GI symptoms, respiratory symptoms		HS, respiratory infections, ILD, bleeding		HS, TCP, bleeding, ILD, liver disease		HS, TCP, atherogenic lipid profile, pulmonary disease		HS, ILD, TCP
Changes over time in chronic ASMD	Chronic visceral disease: platelet counts decreased over time, WBC decreased, total bilirubin increased, no statistically significant changes in lipid profiles		NA		ND		ND		Progressive hypersplenism, worsening atherogenic profile, gradual deterioration in pulmonary function, decrease in platelet and WBC counts		Gradual decrease in platelet count in some patients with chronic neurovisceral and chronic visceral disease; decreased bone marrow fat fractions in chronic visceral disease
Predictors of major morbidity	No statistically significant predictors for infantile neurovisceral form Earlier age at diagnosis and younger gestational age for patients with chronic disease		ND		ND		ND		Phenotypic severity correlated with certain genotypes		ND
Resource use and lifestyle limitations	Hospitalization, mobility status, disability status, schooling, work status, med., procedures, medications: see text for results		ND		Diminished QoL in pediatric patients (multiple scores) and adults (general health)		ND		ND		Follow-up of 6 patients with chronic visceral disease: 1/6 able to work full time

GI gastrointestinal, HS hepatosplenomegaly, ILD interstitial lung disease, med. medical, NA not available, ND not determined, QoL quality of life, TCP thrombocytopenia, WBC white blood cell