Natural history of infantile G(M2) gangliosidosis.
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.
Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Annette E
AE
Bley
Ourania A
OA
Giannikopoulos
Doug
D
Hayden
Kim
K
Kubilus
Cynthia J
CJ
Tifft
Florian S
FS
Eichler
D000367:Age Factors; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003430:Cross-Sectional Studies; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D018450:Disease Progression; D005260:Female; D020143:Gangliosidoses, GM2 / Q000401:mortality* / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016019:Survival Analysis; D013997:Time Factors