Boy aged 9 months referred to the paediatrics clinic for evaluation of progressive abdominal swelling. The parents were not consanguineous and had no relevant medical history. There had been a progressive decrease in the weight and length percentiles of the patient from birth to the time of the evaluation, while his psychomotor development was normal. The patient had been exclusively breastfed on demand in the first two months of life, and was subsequently fed artificial formula, with frequent feedings at two to three hour intervals with no breaks at night. Physical examination revealed a weight of 8kg (3rd–10th percentile), height of 67cm (3rd–10th percentile), Waterlow height-for-age of 94.3%, weight-for-height z-score of −0.44 (WHO standards), and marked abdominal swelling with hepatomegaly of 9cm. These findings led to performance of an abdominal ultrasound scan, which revealed uniform hepatomegaly, and a chemistry panel with the following key findings: AST, 1071U/L (normal range [NR], 0–34); ALT, 573U/L (NR, 10–49); glucose 23mg/dL (NR, 70–100); and triglycerides, 772mg/dL (NR, <110). The patient did not respond to the glucagon stimulation test, with a glucose level before stimulation of 38mg/dL, followed by 40mg/dL 30min after glucagon administration, with no hyperlactacidaemia. Genetic testing was performed due to suspicion of glycogen storage disease, identifying a defect in the α subunit of phosphorylase kinase, which confirmed the diagnosis of glycogen storage disease type IXa. The patient required continuous nocturnal gastric feeding until age 5 years, when the family succeeded in achieving adequate metabolic control.

Girl aged 19 months referred to the paediatrics clinic for failure to thrive between 15 and 18 months of life. The parents were not consanguineous, were originally from Bangladesh, and had no relevant medical history. The patient had a varied diet adequate for her age, and she continued to breastfeed on demand. Her psychomotor development was normal. Physical examination revealed a weight of 9.045kg (3rd–10th percentile), height of 77cm (3rd–10th percentile), Waterlow height-for-age of 95%, weight-for-height z-score of −0.73 SDS (WHO standards), and marked abdominal swelling with hepatomegaly of 8cm. The abdominal ultrasound scan evinced a uniform hepatomegaly. The salient findings of the chemistry panel were AST, 1858U/L; ALT, 1029U/L; glucose, 56mg/dL; and triglycerides, 257mg/dL. In the glucagon test, the glucose level before administration of glucagon was 28mg/dL, and at 30min it was 40mg/dL without hyperlactacidaemia. Genetic testing was requested for suspected glycogen storage disease, which identified amylo-1,6-glucosidase deficiency, leading to diagnosis of type IIIa glycogen storage disease. She required continuous nocturnal gastric feeding for a period of two weeks. Subsequently, thanks to extensive family involvement, the patient achieved adequate metabolic control with feedings at 4h intervals in the daytime, and two cornstarch feedings during the night.

The presence of progressive abdominal swelling in an infant requires ruling out hepatomegaly, among other conditions. In some cases, considerable liver enlargement that can reach as far as the iliac crest is difficult to feel with palpation and may go unnoticed,2 as described in the two cases.

A differential diagnosis of the multiple aetiologies of hepatomegaly can be performed by history taking, physical examination and diagnostic tests.2 In the cases presented here, in addition to hepatomegaly and the marked abdominal swelling, the failure to thrive and the presence of hypertransaminasaemia, hyperlipidaemia and hypoglycaemia with abnormal results in the glucagon test led us to suspect a diagnosis of glycogen storage disease.3

Glycogen storage disease type III is caused by a deficiency of amylo-1,6-glucosidase, also known as glycogen debranching enzyme, an enzyme involved in glycogenolysis whose deficiency leads to accumulation of limit dextrins. In 85% of cases, this deficiency affects the liver and muscle tissues (subtype IIIa).4 Glycogen storage disease type IX results from a defect in the activation of phosphorylase kinase, which is also involved in glycogenolysis. Different mutations may occur in the genes of each of the subunits that compose the enzyme (α, ß, γ, δ) with variable presence in different tissues. X-linked glycogen storage disease type IXb (XLG) is the most frequent form and only involves the liver.5

The main goal of treatment is to prevent hypoglycaemia. This requires avoiding prolonged fasting periods by the frequent intake of slow-release carbohydrates throughout the day, and in some cases, especially in infants, nocturnal gastric feedings.6