Natural history of infantile G(M2) gangliosidosis
Standard
Natural history of infantile G(M2) gangliosidosis. / Bley, Annette E; Giannikopoulos, Ourania A; Hayden, Doug; Kubilus, Kim; Tifft, Cynthia J; Eichler, Florian S.
In: PEDIATRICS, Vol. 128, No. 5, 11.2011, p. e1233-41.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Natural history of infantile G(M2) gangliosidosis
AU - Bley, Annette E
AU - Giannikopoulos, Ourania A
AU - Hayden, Doug
AU - Kubilus, Kim
AU - Tifft, Cynthia J
AU - Eichler, Florian S
PY - 2011/11
Y1 - 2011/11
N2 - OBJECTIVE: G(M2) gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile G(M2) gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature.METHODS: Patients with infantile G(M2) gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature.RESULTS: Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival.CONCLUSIONS: We studied the timing of regression in 97 cases of infantile G(M2) gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions.
AB - OBJECTIVE: G(M2) gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile G(M2) gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature.METHODS: Patients with infantile G(M2) gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature.RESULTS: Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival.CONCLUSIONS: We studied the timing of regression in 97 cases of infantile G(M2) gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions.
KW - Age Factors
KW - Cause of Death
KW - Child
KW - Child, Preschool
KW - Cohort Studies
KW - Combined Modality Therapy
KW - Cross-Sectional Studies
KW - Developmental Disabilities/diagnosis
KW - Disease Progression
KW - Female
KW - Gangliosidoses, GM2/mortality
KW - Humans
KW - Infant
KW - Infant, Newborn
KW - Kaplan-Meier Estimate
KW - Male
KW - Prognosis
KW - Proportional Hazards Models
KW - Risk Assessment
KW - Severity of Illness Index
KW - Surveys and Questionnaires
KW - Survival Analysis
KW - Time Factors
U2 - 10.1542/peds.2011-0078
DO - 10.1542/peds.2011-0078
M3 - SCORING: Journal article
C2 - 22025593
VL - 128
SP - e1233-41
JO - PEDIATRICS
JF - PEDIATRICS
SN - 0031-4005
IS - 5
ER -