Long‐term follow‐up of a new case of liver glycogen synthase deficiency

Abstract

We report a new case of hereditary hepatic glycogen synthase (GS) deficiency (MIM 240600) in a French Canadian girl referred at 7 years of age for a family history of hyperlipidemia. Her initial evaluation incidentally revealed fasting hypoglycemia and ketonuria after a 10-hr fast with normal growth, development, and physical examination. Additional biochemical findings included fasting hypoalaninemia with elevated plasma branched chain amino acids and postprandial hyperlactatemia. Liver glycogen synthase activity was reduced. Unlike most other reported patients, we observed on three different occasions an increase in fasting plasma glucose levels after glucagon administration during episodes of hypoglycemia. At 13 years of age, her growth and intellect are normal; however, she still has hypoglycemia after 18 hr of fasting. From our patient's course and a review of the literature, we conclude: (A) Usual modes of presentation of GS deficiency are non-specific symptoms after overnight fasting (7/17), incidental findings (3/17), or positive family history (7/17); (B) Most patients maintain normal growth (8/11) and intellectual abilities (12/15); (C) Fasting hypoglycemia (17/17) and reduced liver glycogen content (9/9) are constant features; (D) Biochemical findings also include postprandial hyperlactatemia (13/13), fasting hyperketonemia (12/12), and fasting hypoalaninemia (8/9); (E) Glucagon response following fasting hypoglycemia is usually reduced or absent (7/8) but can be repeatedly present (1/8); (F) Liver steatosis is frequent (6/6). Although rare, GS deficiency results in a characteristic biochemical profile that, if recognized, should lead promptly to its diagnosis.

Three Successful Pregnancies in a Patient With Glycogen Storage Disease Type 0

“…GSD 0 can, for several years, remain silent or may take an oligosymptomatic and mild course [7,14] as was the case in our patient who showed rst symptoms only at the age of 3.5 years. Few adolescent and adult patients with GSD 0 have been reported so far, and their clinical course suggests that the fasting tolerance increases with age [6,14]. This was also observed in our patient who presented with hypoglycemia and hyperketonemia in early childhood, but remained well since the age of 8 onwards, as shown by her requiring minimal to no medical follow-up.…”

“…It has been hypothesized that this disease may be underdiagnosed, since asymptomatic siblings have been identi ed in several GSD type 0 families [7,13]. GSD 0 can, for several years, remain silent or may take an oligosymptomatic and mild course [7,14] as was the case in our patient who showed rst symptoms only at the age of 3.5 years. Few adolescent and adult patients with GSD 0 have been reported so far, and their clinical course suggests that the fasting tolerance increases with age [6,14].…”

Glycogen controls Caenorhabditis elegans lifespan and resistance to oxidative stress

“…Chronic inhibition of glycogen phosphorylase in rats causes liver inflammation and damage, supporting the link between glycogen excess and disease53. In contrast, adults with liver glycogen synthase deficiency are typically asymptomatic and rely on gluconeogenesis to meet their glucose needs5455. Thus it is possible that liver glycogen is expendable during adulthood, and excess glycogen resulting from a high carbohydrate diet may actually be harmful.…”

Mutational analysis of the GYS2 gene in patients diagnosed with ketotic hypoglycaemia

“…Almost all children reported so far are small for gestational age (SGA) at birth, and most come to medical attention for subtle problems, such as poor intake, lethargy, short stature or failure to thrive (10,11) . More severe presentations include pallor, lethargy, nausea and sometimes seizures; however, some children may present with normal growth, development and physical examination (12) . GSD0 is a differential diagnosis in children presenting with ketotic hypoglycaemia (9,13) .…”