Hepatic glycogenoses (GH) are rare hereditary metabolic diseases caused by an abnormality in glycogen metabolism, characterized by an enzymatic deficiency, with clinical expression varying according to types, ranging from type I, the most severe form, to type VI, which is a benign late-onset form. GH affect the synthesis of glycogen, its degradation, its use in glycolysis, or its lysosomal metabolism. Since glycogen is primarily present in the liver and muscles, this result in glycogenoses with hepatic or muscular expression, sometimes affecting both tissues (Wolfsdorf et al., 2023).With an incidence of about 1 case per 25,000 births, GH represent approximately 80% of glycogenoses and are more frequent in children. Different types of glycogenoses have been described and identified according to the enzymatic deficiency involved. Types I, III, and IX account for about 80% of hepatic glycogenoses (Colonetti et al., 2019; Akter et al., 2025).

Type I glycogen storage disease is due to a malfunction of glucose-6-phosphatase activity, an enzyme that catalyzes the hydrolysis of G6P into phosphate and glucose, primarily leading to hypoglycemia, hyperlactacidemia, hyperuricemia, and mixed type hyperlipoproteinemia, often at the expense of triglycerides, responsible for hepatic steatosis (Dreyfus, 1993). This enzymatic dysfunction explains the main clinical sign present in patients affected by this type of glycogen storage disease: the defect in short fasting tolerance (Labrune et al., 2015). Hypertriglyceridemia can be significant and cause serious complications dominated by pancreatitis and hepatic adenomas (Terry et al., 2015; Habib, 2022). The aim of this article is to highlight this rare disease as well as its main clinical and biological characteristics, and to report a case of type I glycogen storage disease revealed by significant hypertriglyceridemia.

This is an 8-month-old female infant, with no known consanguinity; her 6-year-old brother is being monitored for type I glycogen storage disease diagnosed at 11 months of age. She was admitted to the Abderrahim El Harouchi mother-child hospital for repeated convulsions due to hypoglycemia, which had been ongoing for 1 month. Clinically, the baby presented with a cherubic face and hepatomegaly measuring 4 finger bread

The biological assessment was as follows: ASAT at 193 UI/l (<45UI/L), ALAT at 179 UI/l (<45UI/L), PAL: 149 (<500UI/L), Gamma-glutamyl trans-ferase: 22 (9-36 UI/L), Major hypertriglyceridemia 

at 15.5 g/l (<1.5 g/l), Total bilirubin: 4 (3-12 mg/l), Conjugated bilirubin: 2.3 (1-4 mg/l), Unconjugated bilirubin: 1.7 (<11.9 mg/l), Total cholesterol at 1.86 g/l (1.5-2 g/l), Blood glucose at 0.95 g/l (0.7-1 g/l), Uric acid at 45 mg/l (35-72 mg/l). 

The liver biopsy showed a slightly decreased glycogen concentration and signs of enzymatic deficiency. Given this clinical and biological picture, the diagnosis of Glycogen Storage Disease Type I was raised. The newborn was placed on an appropriate dietary regimen. A good clinical and biological evolution was observed thereafter.

Clinical and biological characteristics of GHGH are heterogeneous pathologies, both clinically and biologically. The age of discovery ranges from 5 months to 6 years depending on the type of GH. Abdominal distension is the main reason for consultation related to homogeneous hepatomegaly, often associated with stunted growth. They can endanger vital prognosis during acute metabolic decompensations.

Table 1: Classification of GH Froissart et al. (2010).

The biological profile guides the diagnosis. The majority of patients with type I GH present an elevated fasting lactate level associated with severe and recurrent hypoglycemia that can lead to serious neurological and psychomotor complications in the absence of early management (Maire et al., 1991). The lipid profile is generally disturbed with hypertriglyceridemia and hypercholesterolemia resulting from metabolic imbalance. The liver biopsy shows glycogenic overload (PAS+ staining) at the level of the hepatocytes; an important diagnostic tool to confirm the positive diagnosis (Labrune et al., 2015). The determination of the type of glycogenosis is defined by enzymatic assay. The deficiency may concern the glucose-6-phosphatase complex (type I glycogenosis), the debranching enzyme (type III), the branching enzyme (type IV), the phosphorylase system (types VI and IX) or even glycogen synthase (type 0) (Table 1).

Fig. 1: Updated classification of Hepatic Glycogenoses (W. Kiliman) (Kilimann et al., 2015).

Molecular biology is currently used in the diagnostic process and is a valuable aid whether to confirm a diagnosis or to establish it right away, which helps avoid the invasive procedure of a liver or muscle biopsy (Burda et al., 2015).

Discussion of clinical observation Hyperlipidemia is a metabolic anomaly described in glycogenoses type I, the pathophysiology of which is not well understood (Robert et al., 2002). It is generally of a mixed type with hypertriglyceridemia being more pronounced than hypercholesterolemia (Levy et al., 1988).

This hypertriglyceridemia is classified as major if it is greater than 10g/l Nouvel et al. (2013). The excess of G6P, due to its failure to be converted into glucose, will subsequently be used in other metabolic pathways. Glycolysis is increased with a high production of lactate and excess formation of acetyl-CoA, which subsequently stimulates de novo lipogenesis and cholesterol synthesis. Roseline (Froissart, 2010). 

Table 2: Most frequent mutations in GH Ia (American College of Medical Genetics and Genomics) (Kishnani et al., 2010).

The decrease in insulin stimulates lipolysis and leads to the release of free fatty acids into the plasma (Robert et al., 2002). A large soft liver associated with intolerance to fasting and a high triglyceride level (> 20g/l) strongly supports the diagnosis of type I glycogenosis (Alepa et al., 1967; Labrune et al., 2010). Our infant presented a typical clinical and biological picture, strongly suggesting the diagnosis of glycogen storage disease type I. Type I GH can lead to other complications such as acute pancreatitis and hepatic adenoma (Terry et al., 2015).

Table 3: Most frequent mutations in GH Ib (American College of Medical Genetics and Genomics) (Kishnani et al., 2010).

 The European study on glycogen storage disease type I (ESGSD1) involving 231 cases showed that 3 of the patients developed acute pancreatitis due to their hypertriglyceridemia Rake et al. (2002) This risk increases if the triglyceride level is above 5 g/l (Wang et al., 2011). Subsequently, triglycerides are an excellent marker for long-term monitoring of type I GH, as an increase signifies poor metabolic control due to a poor diet, or the association with other comorbidities such as hypothyroidism (Terry et al., 2015). According to the recommendations of ESGSD1, triglycerides should be less than 5.3 g/l to avoid any complications, and a regular monitoring schedule of biological TG levels and lipid profile should be followed according to the child's age (Table 4) (Labrune et al., 2010).

Table 4: The monitoring rhythm of the lipid profile according to age Labrune et al (2010).

Evolution and Management

The complications of GH are formidable, particularly liver cirrhosis, which is rare but fatal in the absence of liver transplantation. The occurrence of mental deficiency is strongly correlated with the occurrence of hypoglycemia during the neonatal period and in childhood (Brown et al., 2015). Dietary management is the most important aspect of care, aimed at ensuring a regular and balanced intake of carbohydrates to counter episodes of hypoglycemia and to guarantee metabolic balance. Constant Rate Enteral Nutrition (CREN) is an interesting therapeutic measure that allows for better therapeutic adherence, but remains rarely practiced in this context to this day (Charrière, 2018). The progress in monitoring and treating patients with GH has currently allowed children to reach adulthood, whereas a few decades ago, they died much earlier, before the age of 10.

Hepatic glycogenoses are rare hereditary metabolic diseases with serious consequences. Major hypertriglyceridemia can guide the diagnosis.A delay in the diagnosis of these diseases can lead to death in the absence of urgent care, whereas early diagnosis often allows for a reversal of the prognosis. Regular measurement of triglycerides and the lipid profile constitutes a good marker for monitoring and prognosis of hepatic glycogenoses. The quality of treatment is closely dependent on the speed of diagnosis and a strong cooperation between expert clinicians and specialized biologists.

A.M.: Writing of the Article ; N.K.: Design of the research protocol, interpretation of results, correction of the work; I.C.: Data collection and article review ; M.E.: Data collection and literature research.

Many thanks to Prof. Imane Chahid and the entire Pediatrics 3 team, Mother-Child Hospital Abder-rahim Harouchi, Ibn Rochd University Hospital, Casablanca, Morocco.

The authors declare that they have no conflicts of interest related to this article.