Natural history of infantile G(M2) gangliosidosis

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 -