A Concise Review of Ketogenic Dietary Interventions in the Management of Rare Diseases

Table 3

Summary of case report and case series found in the literature regarding use of KD in glycogen storage diseases.

Type of glycogen storage disease	Author	Year	Patient characteristics	Traditional treatment method	Dietary modification	Results
Type IIIa	Brambilla et al. [31]	2014	Two siblings (girl and boy), 7 and 5 years old, both with left ventricular hypertrophy	Frequent diurnal and nocturnal hyperproteic meals followed by orally administered uncooked corn starch	High-fat (60%), high-protein (25%), and low-carbohydrate (15%) diet.	Both patients showed a relevant reduction of the thickness of interventricular septum, left ventricle posterior wall, and an improvement of the outflow obstruction.
Type IIIa	Mayorandan et al. [1]	2014	2 boys (9 and 11 years)	Frequent feeds with carbohydrate-rich meals or continuous enteral feeding	A modified Atkins diet (10 g carbohydrate per day, protein, and fatty acids ad libitum) over a period of 32 and 26 months, respectively, in 9 years old and 11 years old.	Creatine kinase levels in blood dropped in response to Atkins diet. One patient suffered from severe cardiomyopathy which significantly improved under the diet. Apart from transient hypoglycaemia, no serious adverse effects were observed.
Type IIIa	Francini et al. [32]	2019	A 34-year-old male patient with hypertrophic cardiomyopathy	High-carbohydrate diet	Modified Atkins diet (MAD) providing up to 20 g carbohydrate per day which is roughly equivalent to a ratio of 1-2 : 1 of fat to protein plus carbohydrates.	After 12 months of treatment, ejection fraction raised from 30 to 45%, liver enzymes were reduced, and CK plasma level dropped from 568 to 327 U/l. Physical activity increased from about 1300 to 2800 steps per day, and health-related quality of life assessment ameliorated. An increase in the uric acid triglycerides plasma level was observed.
Type IIIa	Olgac et al. [33]	2020	6 patients, aged 3–31 years	Frequent feeds with high complex carbohydrates in small children and a low-carb-high-protein diet in older children and adults	Modified Atkins diet.	In all patients, transaminase levels dropped in response to MAD. Decrease in CK levels was detected in 5 out of 6 patients. Hypoglycemia was evident in 2 patients but was resolved by adding uncooked corn starch to diet.
Type IIIa	Marusic et al. [35]	2020	A 15-year-old girl with left ventricular obstructive hypertrophy	Frequent corn starch meals	Diet consisted of ketogenic ratios of 2.5 : 1; fats (5.2 g/kg/d) contributed 87% daily calories, proteins (1.6 g/kg/d) contributed 11%, and carbohydrates (0.3 g/kg/d) contributed 2%. Continuous ketosis was maintained for over 4 years.	Cardiac MRI was repeated after 16 and after 40 months, showing a normalization of left ventricular parameters, with a decrease of the total left ventricular mass index (LVMI) (from 58 g/m^2 to 37 g/m^2) without residual outflow obstruction. Finally, no hypoglycemic events were recorded while on KD.
Type V	Vorgerd et al. [30]	2002	A 55-year-old male	Carbohydrate-based diet	Creatine supplementation and ketogenic diet (increasing the fat content of his diet to 80% with 14% protein (1 g/kg/d) in total).	With a continuous one-year diet, his exercise tolerance was 3- to 10-fold increased, dependent of the endurance level. Maximum strength and activity duration also improved, and CK levels dropped from 5.300 U/l to 890 U/l on ketogenic diet.
Type V	Reason et al. [36]	2017	3 patients (a 54-year-old male, a 12-year-old female, and a 45-year-old female)	Care as usual	Low-carbohydrate ketogenic diet for 6 months.	Distinct improvement in activity and exercise tolerance was found. Plasma creatine kinase (CK) was significantly lowered in all three cases, with two patients exhibiting values within normal range. Overall, each patient described an improved quality of life.
Type V	Lokken et al. [37]	2019	8 patients	Care as usual	Participants were randomized to follow one of the three KD regimes for 3 weeks (#1: 65%/15%/20%; #2: 75%/15%/10%, or #3: 80%/15%/5%, fat/protein/carbohydrate).	Five patients reported subjective symptom relief. All diet regimes seemed to improve fatty acid oxidation rates and exercise capacity.