L-alanine supplementation in Pompe disease (IOPD): a potential therapeutic implementation for patients on ERT? A case report

Abstract

Background: Pompe disease (PD) is a disorder of glycogen metabolism conditioning a progressive and life conditioning myopathy. Enzyme replacement therapy (ERT) is currently the best treatment option for PD, but is not resolutive. While other potential therapeutic approaches have been reported before, these have never been tried as co- treatments. L-alanine oral supplementation (LAOS) has been proven to reduce muscle breakdown: we hereby report the first case of supplementation on a PD patient on ERT.

Case presentation: F. is a 9 y.o. infantile onset Pompe Disease (IOPD) girl ERT-treated since age 1 developing a progressive myopathy. We started her on LAOS and performed assessments at baseline, 6 and 9 months. At baseline, F.'s weight, height and BMI were within normal ranges, while body composition showed low fat mass -FM and high resting energy expenditure-REE levels. After LAOS, a progressive FM increase and REE reduction could be observed both at 6 and 9 months.

Conclusions: ERT is not curative for PD patients thus additional treatments could be considered to improve outcomes. Our patient showed physical signs of inability to accumulate energy when exclusively on ERT, while FM increase and REE reduction occurred when supplemented with LAOS, likely reflecting anabolic pathways' implementation. This is the first case reporting potential LAOS benefits in PD-on ERT patients. Longitudinal case control studies are yet needed to evaluate possible efficacy of combined LAOS And ERT treatment in PD patients.

Keywords: Body composition; Enzyme replacement therapy; L-alanine; Myopathy; Pompe Disease.

Fig. 1

Time-REE correlations with LAOS, patient on treatment vs. expected patient’s REE without intervention. Shapiro–Wilk normality test and repeated-Measures ANOVA were performed (with statistical significance p-value set at < 0.05) for studying the variables at each studied time with data grouped into two categories. First group contained the variables of basal metabolism repeated at 3 times of our patient (red line). Second group contained instead the expected basal metabolism variables without intervention, obtained with three different formulas* (Harris Benedict-REE; Schofield-REE; WHO-REE) at same three different times and based on patient’s parameters (black line). A statistically significant association can be found between intervention and time with the basal metabolism of our patient (p-value 0.004)