Substrate reduction therapy with miglustat in chronic GM2 gangliosidosis type Sandhoff: results of a 3-year follow-up.
GM2 gangliosidosis type Sandhoff is caused by a defect of beta-hexosaminidase, an enzyme involved in the catabolism of gangliosides. It has been proposed that substrate reduction therapy using N-butyl-deoxynojirimycin (miglustat) may delay neurological progression, at least in late-onset forms of GM2 gangliosidosis. We report the results of a 3-year treatment with miglustat (100 mg t.i.d) in a patient with chronic Sandhoff disease manifesting with an atypical, spinal muscular atrophy phenotype. The follow-up included serial neurological examinations, blood tests, abdominal ultrasound, and neurophysiologic, cognitive, brain, and muscle MRI studies. We document some minor effects on neurological progression in chronic Sandhoff disease by miglustat treatment, confirming the necessity of phase II therapeutic trials including early-stage patients in order to assess its putative efficacy in chronic Sandhoff disease.
Masciullo
Marcella
M
Department of Neuroscience, Catholic University of Sacred Heart, Rome, Italy.
Santoro
Massimo
M
Modoni
Anna
A
Ricci
Enzo
E
Guitton
Jerome
J
Tonali
Pietro
P
Silvestri
Gabriella
G
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D009460:Neurologic Examination; D011237:Predictive Value of Tests; D012497:Sandhoff Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D013997:Time Factors; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin; C059896:miglustat; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase
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