Normoglycemic Ketonemia as Biochemical Presentation in Ketotic Glycogen Storage Disease

Abstract

Background: According to the textbooks, the ketotic glycogen storage disease (GSD) types 0, III, VI, IX, and XI are associated with fasting ketotic hypoglycemia and considered milder as gluconeogenesis is intact.Methods: A retrospective cohort study of biochemical profiles from supervised clinical fasting studies is performed in ketotic GSD patients in our metabolic center. For data analysis, hypoglycemia was defined as plasma glucose concentration <2.6 mmol/L. Total KB was defined as the sum of blood acetoacetate and b-hydroxybutyrate concentrations. If the product of glucose and KB concentrations was greater than 10, a ketolysis defect was suspected.Results: Data could be collected from 13 fasting studies in 12 patients with GSD III (n ¼ 4), GSD VI (n ¼ 3), and GSD IX (n ¼ 5). Six patients remained normoglycemic with median glucose concentration of 3.9 mmol/L (range, 2.8-4.6 mmol/L) and median total KB concentration of 1.9 mmol/L (range, 0.6-5

Glycogen storage diseases: Diagnosis, treatment and outcome

“…Patients present in infancy or early childhood with varying degrees of growth retardation and prominent hepatomegaly secondary to excessive liver glycogen. Ketotic hypoglycemia or just hyperketosis occur with prolonged fasting or strenuous exercise [110]. Because gluconeogenesis is preserved, hypoglycemia tends to be mild.…”

Deep morphological analysis of muscle biopsies from type III glycogenesis (GSDIII), debranching enzyme deficiency, revealed stereotyped vacuolar myopathy and autophagy impairment

“…During adolescence and adulthood, patients develop a progressive myopathy that can be accompanied by muscle weakness and exercise intolerance [3, 20]. In this phase, the metabolic impairment is less prominent and the patients are referred to muscle specialists [3–9]. A minor percentage (15%) of patients develop cardiomyopathy [21] and other liver complications such as cirrhosis.…”

Review article: Accelerated starvation of childhood: Have I judged ketones?

“…It may be that a heterogenous group of metabolic disorders are contributing factors . Glycogen synthase deficiency, other glycogen storage disorders and monocarboxylate transporter 1 deficiency are three such contributors. Affected children are thought by some researchers to be those with metabolic processes that are slow to develop and may represent the tail of the Gaussian curve of metabolic maturity .…”

“…32 Drug toxicity (e.g. salicylates), 33 inborn errors of metabolism, 15,34 anorexia nervosa 35 and low-carbohydrate diets designed to induce mild ketosis may also trigger ketoacidosis. 36 Other forms of euglycaemic or hypoglycaemic ketosis are described in adults after alcohol binges, 35,37 while pregnant 17,35,38 and during lactation.…”

“…Under the banner of 'KH' much of the research focus, even into the 21st century, has been on those children who present with hypoglycaemia in concert with their ketosis, 2 although some researchers had acknowledged that ketosis is not always accompanied by hypoglycaemia. [13][14][15] The prevalence of hypoglycaemia in nondiabetic patients 1-5 years old presenting to the ED has been reported as 6.54 per 100 000 presentations when defined as <2.6 mmol/L, 16 and hypoglycaemia with ketosis ('KH') has been found in approximately 4 per 100 000 presentations in retrospective studies. 2,16 However, in our experience, the prevalence of ketosis with euglycaemia is much higher (Box 2).…”