Development of high sustained anti-drug antibody titers and corresponding clinical decline in a late-onset Pompe disease patient after 11+ years on enzyme replacement therapy.

A late-onset Pompe disease patient developed high sustained antibody titers (HSAT) of ≥51,200 after 11+ years on alglucosidase alfa and previous tolerance. There was a corresponding worsening of motor function and rise in urinary glucose tetrasaccharide (Glc4). Following immunomodulation therapy, HSAT were eliminated with improved clinical outcomes and biomarker trends. This report highlights the importance of continued surveillance of antibody titers and biomarkers, the negative impact of HSAT, and improved outcomes with immunomodulation therapy.

Pegvaliase dose escalation to 80 mg daily may lead to efficacy in patients who do not exhibit an optimal response at lower doses.

In 2018, pegvaliase was approved as the first enzyme substitution treatment for phenylketonuria (PKU) and is now the second medication available for PKU patients since the approval of sapropterin dihydrochloride in 2007. Historically, dietary management has been the mainstay of treatment for PKU. While sapropterin response rate is limited to approximately 50% of PKU patients, pegvaliase has the potential to reduce phenylalanine levels in all PKU patients (Vockley et al., 2014; Longo et al., 2019 [1,3]). Current FDA labeling for pegvaliase includes a dose maximum of 60 mg daily (Longo et al., 2019; BioMarin Pharmaceutical Inc., 2020 [3,4]). We report a case series of four phenylalanine hydroxylase (PAH) deficient patients, previously treated with dietary management only, who initiated treatment with pegvaliase and were titrated to 80 mg daily dosing. The safety profile in these four cases did not differ from lower maintenance dosing (Longo et al., 2019 [3]). Subsequent decreases in Phe levels were observed on 80 mg maintenance dosing, allowing for individualized dietary liberalization in three out of four patients. We conclude that pegvaliase dosing must be personalized to achieve therapeutic goals and that some patients may require higher doses than those included on the product label.

CE: Understanding the Nurse's Role in Managing Gaucher Disease.

: Lysosomal storage disorders (LSDs) are a group of inherited metabolic conditions, the overall incidence of which is estimated to range from one in 5,000 to one in 7,000 live births. Gaucher disease, the most common LSD, is of autosomal recessive inheritance. It results from a deficiency of acid ß-glucocerebrosidase and can affect the spleen, liver, bone, bone marrow, and central nervous system. Gaucher disease is clinically classified into one of three phenotypes, depending on the absence or presence of neurodegenerative disease and the rate of disease progression. Although there is no cure for Gaucher disease, it may be treated with enzyme replacement and substrate reduction therapy. With the development of enzyme testing through dried blood spots, Gaucher disease may now be detected at birth through newborn screening. The purpose of this article is to review the epidemiology and pathophysiology of Gaucher disease, update nurses on advances in newborn screening, diagnosis, and management of this genetic disorder, and highlight the role of nurses in the diagnosis and care of patients with Gaucher disease.