A High-Fat, High-Protein, Carbohydrate-Restricted Dietary Interventions in Pompe Disease: A Case Series with...

Pompe disease (PD) is a lysosomal storage disorder characterized by progressive glycogen accumulation leading to cardiomyopathy and motor decline. Despite the survival benefits of enzyme replacement therapy (ERT), the long-term clinical course is often complicated by persistent skeletal muscle pathology, necessitating effective adjunctive interventions. This study aimed to evaluate the clinical utility of a high fat, high protein, carbohydrate-restricted dietary intervention in patients with PD.

Data collected included the initial and duration of dietary treatment, total caloric intake, macronutrient distribution, the ratio of fat to carbohydrate plus protein and any reported adverse effects, such as weight loss, micronutrient deficiencies.

Twelve patients (7 IOPD, 5 LOPD; median diet initiation age: 14 months for IOPD, 52 months for LOPD) maintained individualized carbohydrate-restricted, high-fat dietary therapies for >3 months, with a median follow-up duration of 23.5 (range, 3-48) months. Dietary protocols ranged from classic ketogenic diet to modified Atkins and low-carbohydrate high-fat regimens, providing 54-82% of total daily energy from fat alongside a high absolute protein intake (1.7-4.0 g/kg/day) to prevent muscle catabolism. All patients received concurrent ERT, except one LOPD patient managed exclusively with dietary therapy. The median duration of diet was 23.5(3-48) months. Stabilization or mild-to-moderate improvements in motor function, proximal muscle strength, and physical endurance (e.g., 6-minute walk test distance) were achieved across follow-up. The dietary interventions were well tolerated with no serious diet-related adverse events. A significant reduction in creatine kinase (CK) levels was observed between baseline and the third month of the diet (p=0.015). No serious adverse effects were observed.

These real-world findings suggest that a high fat, high protein, carbohydrate-restricted dietary approaches may serve as feasible adjunctive therapies in the management of PD. Further prospective and controlled studies are warranted to clarify their long-term efficacy, safety, and metabolic impact.