TY - JOUR T1 - Eye movement impairment recovery in a Gaucher patient treated with miglustat. JF - Neurol Res Int Y1 - 2010 A1 - Accardo, Agostino A1 - Pensiero, Stefano A1 - Ciana, Giovanni A1 - Parentin, Fulvio A1 - Bembi, Bruno AB -

In Gaucher Disease (GD) the enzyme (imiglucerase) replacement therapy (ERT) is not able to stop the progression of the neurological involvement, while the substrate reduction therapy (SRT), performed by N-Butyldeoxynojirimycin (miglustat), is an alternative that should be evaluated. Two sisters, presenting the same genotype (R353G/R353G), were diagnosed as suffering from GD; one of them later developed neurological alterations identified by quantitative saccadic eye movements analysis. The aim of the study was to quantitatively measure the miglustat effects in this GD neurological patient. Eye movement analysis during subsequent controls was performed by estimating the characteristic parameters of saccadic main sequence. The study demonstrates that the SRT alone can be effective in GD3. Moreover, it confirms that quantitative eye movement analysis is able to precociously identify also slight neurological alterations, permitting more accurate GD classification.

VL - 2010 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21152212?dopt=Abstract ER - TY - JOUR T1 - Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II. JF - J Inherit Metab Dis Y1 - 2010 A1 - Bembi, Bruno A1 - Pisa, Federica Edith A1 - Confalonieri, Marco A1 - Ciana, Giovanni A1 - Fiumara, Agata A1 - Parini, Rossella A1 - Rigoldi, Miriam A1 - Moglia, Arrigo A1 - Costa, Alfredo A1 - Carlucci, Annalisa A1 - Danesino, Cesare A1 - Pittis, Maria Gabriela A1 - Dardis, Andrea A1 - Ravaglia, Sabrina KW - Adolescent KW - Adult KW - Age of Onset KW - Aged KW - alpha-Glucosidases KW - Child KW - Enzyme Replacement Therapy KW - Female KW - Follow-Up Studies KW - Glycogen Storage Disease Type II KW - Humans KW - Male KW - Middle Aged KW - Observation KW - Time Factors KW - Treatment Outcome KW - Young Adult AB -

OBJECTIVES: Type II glycogenosis (GSDII) is a lysosomal storage disorder due to acid alpha-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase (rhGAA) has been demonstrated to be effective in the treatment of infantile forms of GSDII, but little information is available concerning late-onset phenotypes. Long-term follow-up studies are not available at present. The aim of this study was to evaluate the ERT long-term effects in late-onset GSDII.

METHODS: Twenty-four patients, including 7 juveniles and 17 adults, received bi-weekly infusion of rhGAA (20 mg/kg) for at least 36 months. Clinical conditions, muscular function (6-min walking test, 6MWT; Walton scale, WS), respiratory function (vital capacity, VC; forced expiratory volume, FEV1; arterial pCO(2)), and muscle enzymes were assessed every 6 months.

RESULTS: The 6MWT improved in both juvenile and adult patients (p = 0.01, p = 0.0002, respectively), as well as in patients with moderate to severe muscle function impairment (WS >3.5; p = 0.002). An overall improvement in WS was also observed (p = 0.0003). VC and FEV1 remained unchanged, while pCO(2) decreased (p = 0.017). Muscle enzymes decreased significantly (p < 0.0001). Two patients (8%) showed transient secondary events during ERT.

CONCLUSIONS: Long-term ERT with rhGAA was shown to be safe, well tolerated, and effective in improving motor function and in stabilizing respiratory function in late-onset GSDII. The response pattern showed a progressive clinical improvement during the follow-up period in juvenile patients, while in adults it reached and maintained a plateau after the first year of treatment.

VL - 33 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20838899?dopt=Abstract ER -