Successful Treatment of Severe Cardiomyopathy in Glycogen Storage Disease Type III With D,L-3-Hydroxybutyrate, Ketogenic and High-Protein Diet

Abstract

Glycogen storage disease type III (GSD III) due to debranching enzyme deficiency presenting usually with hepatomegaly and hypoglycemia may be responsible for severe cardiomyopathy which is often fatal. Current treatment of GSD III is based on frequent high-carbohydrate meals that have no effect on the cardiomyopathy. We describe a 2-mo-old infant presenting with a familial form of GSD III complicated with cardiomyopathy. As conventional treatment was unable to improve his sister's cardiomyopathy who was deceased at age 11 mo, we proposed an experimental treatment combining the use of synthetic ketone bodies (D,L-3-OH butyrate) as an alternative energy source, 2:1 ketogenic diet to reduce glucose intake and high-protein diet to enhance gluconeogenesis. Twentyfour months after the onset of this treatment, echocardiography showed an improvement of cardiomyopathy. Growth and liver size remained normal, and no side effects were observed. Blood glucose levels remained within the normal range and insulin levels decreased. These findings show that synthetic ketone bodies as well as lowcarbohydrate, high-lipid, and high-protein diet may be a more beneficial therapeutic choice therapeutic choice for GSD III patients with cardiomyopathy. These encouraging data need to be confirmed in more GSD III patients presenting with cardiac or muscular symptoms. (Pediatr Res 70: 638-641, 2011)

Heart Failure Due to Severe Hypertrophic Cardiomyopathy Reversed by Low Calorie, High Protein Dietary Adjustments in a Glycogen Storage Disease Type IIIa Patient

“…To our knowledge, a similar case has been reported recently in a pediatric patient (Valayannopoulos et al 2011), and once in an adult patient by Dagli et al in 2009(Dagli et al 2009). The latter describes a 22-year-old male with severe GSD III-related cardiomyopathy treated with a high protein diet in which overtreatment with cornstarch was avoided.…”

Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency–related leukodystrophy

“…It aims at replacing the deficient endogenous ketone body production, needed not only for energy supply, but possibly more so for the synthesis of complex cell and tissue components such as myelin in the central nervous system. Its use was first reported in an abstract by Bonham et al (10), in MADD, and subsequently in other conditions, such as treatment-refractory hypoglycaemia due to hyperinsulinism (11) and severe cardiomyopathy in glycogenosis type III (12). In 2003, Van Hove et al (13) published three patients with MADD, one with predominant leukodystrophy and two with cardiomyopathy who responded very well to treatment with NaHB.…”

Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for glycogen storage disease type III

“…The benefit of a high protein diet or a combined ketogenic/ high protein diet in reversing cardiomyopathy was reported recently as a single case report [9,10]. Thus, there is no definitive therapy for this progressive condition.…”