Patients diagnosed with a genetic disorder also want secondary findings

see Patient decisions for disclosure of secondary findings among the first 200 individuals undergoing clinical diagnostic exome sequencing

In a report that may add fuel to the ethical debate over whether and how to return secondary findings to patients, Shahmirzadi et al. found that, among 200 families seeking diagnostic exome sequencing in a commercial clinical setting, an overwhelming majority wanted a report on secondary findings as well. In the first published study of its kind, the authors analyzed preferences for receiving secondary findings among those seeking a genetic diagnosis after referral by a genetic counselor. The patients—161 severely affected children and 39 adults with less serious illnesses—and their families received genetic counseling prior to testing and signed consent forms that asked specifically about four categories of potential secondary findings: carrier of recessive disorders, predisposition to later-onset disease, predisposition to higher cancer risk, and early-onset disease. All but one adult chose to receive secondary findings in at least one category, and six adults abstained from hearing results in at least one category. Parents and guardians were given the option to receive secondary findings only about early-onset disease; seven chose not to receive that information. The authors point out that these results may not be generalizable because all the patients were dealing with chronic and/or life-threatening illnesses, which may color outlook on future risk of illness. They also suggest that the variation between the guardians’ and adults’ choices may reflect a difference between information parents would like to learn about their children and information that adults would like to learn about themselves. —Karyn Hede, News Editor

Two enzyme treatments for Gaucher disease type 1 have similar safety profiles

see A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability

A real-world evaluation of two commercial forms of enzyme therapy for treatment of Gaucher disease type 1 (GD1) revealed nearly identical safety profiles, according to results reported in this issue. Pastores et al. evaluated patients who transitioned from one form of glucocerebrosidase, imiglucerase, to another, velaglucerase alfa, during a worldwide shortage of imiglucerase caused by temporary shutdown of a manufacturing facility in 2009. The observational study involved 211 GD1 patients with varying exposure to velaglucerase alfa, which was an investigational drug at the time. GD1, an autosomal recessive lysosomal storage disease due to mutations in the encoding gene (GBA1), requires lifetime infusion of glucocerebrosidase. At the time of the study, imiglucerase was the only treatment approved by the US Food and Drug Administration. The study addressed such safety concerns as generation of neutralizing antibodies to the medication and adverse events related to infusion and other treatments. Almost all the patients (189) completed the protocol. Inhibition was very low, and essentially identical for anti-imiglucerase and anti–velaglucerase alfa neutralizing antibodies. Only 3 of the patients who discontinued treatment with velaglucerase alfa did so because of an adverse event suspected of being related to the drug. The authors of the study reported payments from the company sponsoring the study, the maker of velaglucerase alfa. —Karyn Hede, News Editor