7 research outputs found
Real-World Experiences with Taliglucerase Alfa Home Infusions for Patients with Gaucher Disease: A Global Cohort Study
Taliglucerase alfa is an enzyme replacement therapy approved for Gaucher disease. We assessed the duration/compliance/safety of such home infusions in commercial use in four countries where home infusion programs are available. The treatment duration/compliance study included 173 patients (Israel, 58; US, 61; Brazil, 48; Australia, 6) who received ≥1 taliglucerase alfa home infusion through 6/2021. The median age at home therapy initiation was 38 (range, 2–87) years; 58% were females. The median treatment duration (at home) was 2.7 (range, 0.04–9.0) years. The annual compliance rate was stable (≥95%) throughout the study period. A search of the Pfizer global safety database (through 6/2021), identified 19 adverse events (AEs) as related to “definite home use” and 14 to “possible home use” of taliglucerase alfa; 42.4% of these AEs were serious; none were fatal. Twelve serious AEs in five separate case reports were considered treatment related: one case of chest discomfort/pain and hypertension and one case of erythema associated with a toe blister, for which causality could not be excluded; pain in extremity; projectile vomiting and chills, alongside excessive eye blinking; and an infusion-related AE (pruritus). In conclusion, this real-life global study demonstrated that taliglucerase alfa home infusions are safe with high compliance rates
Improved diagnostics by exome sequencing following raw data reevaluation by clinical geneticists involved in the medical care of the individuals tested
Major and minor life events, personality and psychopathology in children with tourette syndrome
When phenotype does not match genotype: importance of “real-time” refining of phenotypic information for exome data interpretation
Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1
Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423 : genotype-phenotype study in neurofibromatosis type 1
Clinical spectrum of individuals with pathogenic NF1 missense variants affecting p.Met1149, p.Arg1276, and p.Lys1423: genotype-phenotype study in neurofibromatosis type 1
We report 281 individuals carrying a pathogenic recurrent NF1 missense variant at p.Met1149, p.Arg1276, or p.Lys1423, representing three nontruncating NF1 hotspots in the University of Alabama at Birmingham (UAB) cohort, together identified in 1.8% of unrelated NF1 individuals. About 25% (95% confidence interval: 20.5-31.2%) of individuals heterozygous for a pathogenic NF1 p.Met1149, p.Arg1276, or p.Lys1423 missense variant had a Noonan-like phenotype, which is significantly more compared with the "classic" NF1-affected cohorts (all p < .0001). Furthermore, p.Arg1276 and p.Lys1423 pathogenic missense variants were associated with a high prevalence of cardiovascular abnormalities, including pulmonic stenosis (all p < .0001), while p.Arg1276 variants had a high prevalence of symptomatic spinal neurofibromas (p < .0001) compared with "classic" NF1-affected cohorts. However, p.Met1149-positive individuals had a mild phenotype, characterized mainly by pigmentary manifestations without externally visible plexiform neurofibromas, symptomatic spinal neurofibromas or symptomatic optic pathway gliomas. As up to 0.4% of unrelated individuals in the UAB cohort carries a p.Met1149 missense variant, this finding will contribute to more accurate stratification of a significant number of NF1 individuals. Although clinically relevant genotype-phenotype correlations are rare in NF1, each affecting only a small percentage of individuals, together they impact counseling and management of a significant number of the NF1 population