A lower energetic, protein and uncooked cornstarch intake is associated with a more severe outcome in glycogen storage disease type III: an observational study of 50 patients

Abstract

Background Glycogen storage disease type III (GSDIII), due to a deficiency of glycogen debrancher enzyme (GDE), is particularly frequent in Tunisia. Phenotypic particularities of Tunisian patients remain unknown. Our aim was to study complications of GSDIII in a Tunisian population and to explore factors interfering with its course. Methods A retrospective longitudinal study was conducted over 30 years (1986–2016) in the referral metabolic center in Tunisia. Results Fifty GSDIII patients (26 boys), followed for an average 6.75 years, were enrolled. At the last evaluation, the median age was 9.87 years and 24% of patients reached adulthood. Short stature persisted in eight patients and obesity in 19 patients. Lower frequency of hypertriglyceridemia (HTG) was associated with older patients (p<0.0001), higher protein diet (p=0.068) and lower caloric intake (p=0.025). Hepatic complications were rare. Cardiac involvement (CI) was frequent (91%) and occurred early at a median age of 2.6 years. Severe cardiomyopathy (50%) was related to lower doses of uncooked cornstarch (p=0.02). Neuromuscular involvement (NMI) was constant, leading to a functional discomfort in 64% of cases and was disabling in 34% of cases. Severe forms were related to lower caloric (p=0.005) and protein intake (p<0.015). Conclusions A low caloric, protein and uncooked cornstarch intake is associated with a more severe outcome in GSDIII Tunisian patients. Neuromuscular and CIs were particularly precocious and severe, even in childhood. Genetic and epigenetic factors deserve to be explored.

Beneficial Effects of Modified Atkins Diet in Glycogen Storage Disease Type IIIa

“…The prevalence of cardiac involvement in GSD IIIa varies in the literature from 31 to 95% [3,16]. Mogahed et al [21] have found cardiac incidence in GSD IIIa patients to be low and independent from neuromuscular involvement, similar to our patient group, where 2 out of 6 had cardiomyopathy with variable CK levels.…”

“…Especially, in the adult patient, the decrease was slight, although its levels remained stable during MAD. It is well known that transaminase levels tend to decrease with age in GSD IIIa as demonstrated earlier in a large series of patients by Chehida et al [16]. The stable progress of aspartate aminotransferase and alanine aminotransferase and the relatively small change in transaminases under MAD, when compared to CK levels, may be characteristics of GSD IIIa.…”

“…Although frequent feeding is needed to prevent hypoglycemia, carbohydrate-rich diets may induce insulin secretion; suppress lipolysis, ketolysis, and gluconeogenesis; and induce glycogen synthesis, leading to the depletion of energy resources in the skeletal muscle and heart [5, 6, 15]. Hyperinsulinism has been debated to play a role in the development of cardiomyopathy in GSD IIIa, especially in patients who are excessively fed with carbohydrates due to high insulin secretion, impairing energy metabolism of the heart [15, 16]. Therefore, recently, diets rich in fat content (e.g., KD and MAD) have been suggested to improve clinical outcome by facilitating ATP generation by the utilization of KBs as an alternative source of energy.…”

Narrative review of glycogen storage disorder type III with a focus on neuromuscular, cardiac and therapeutic aspects

“…In the Sentner cohort, aged 0.3 to 64.2 years (median 19.3 years), only 15% of all patients developed hypertrophic cardiomyopathy 1 . The rate or significance of symptomatic cardiac disease may be higher in some cohorts depending on various factors, including but not limited to age, environmental influences, genetic background or the dietary regimen 11 . For example, among the 50 patients of the Ben Chehida cohort, 11 followed for a mean duration of 6.75 years (range: 1 month to 26.5 years), 56% presented a symptomatic cardiomyopathy at some point during the follow‐up, 11 in some cases severe, and one patient with severe ventricular hypertrophy died of congestive heart failure.…”

Molecular Diagnosis of Panel-Based Next-Generation Sequencing Approach and Clinical Symptoms in Patients With Glycogen Storage Disease: A Single Center Retrospective Study

“…Based on the laboratory data, GSD III is more likely to present with elevated CK levels than GSD I and GSD IX. An elevated CK level is considered a possible serological marker of GSD III (18). Patients with GSDI had higher serum TG, UA, and rGGT levels than patients with GSDIII and GSD IX.…”