A patient with glycogen storage disease type Ia combined with chronic hepatitis B infection: a case report

Abstract

Background: Glycogen storage disease type I (GSD I), also known as von Gierk disease, is a metabolic disorder leading to the excessive accumulation of glycogen and fat in organs, characterized by hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, puberty delay and growth retardation, which can be indicated by height, weight, blood glucose and blood lipids.

Case presentation: Here we present a 16-year-old male patient with GSD Ia complicated with hepatic adenoma and combined with hepatitis B. As a chronic hepatitis B patient, the patient was admitted to hospital in order to further clarify the nature of hepatic space occupancy because of suspicion of hepatocellular carcinoma. However, the imaging studies did not support hepatocellular carcinoma certainly. And by tracing his clinical history, we suggested that he might suffer from GSD I. Finally the diagnosis was confirmed by MRI (Gd-EOB-DTPA), liver biopsy and whole exome sequencing (WES). The WES discovered a homozygous point mutation at the exon 5 of G6PC gene at 17th chromosome, c.G648 T (p.L216 L, NM_000151, rs80356484). This pathogenic mutation causes CTG changing to CTT at protein 216. Though both codons encode leucine, this silent mutation creates a new splicing site 91 bp downstream of the authentic splice site. According to previous research, this mutation is a disease causal variant for GSD Ia, and has a high frequency among GSD patients in China and Japan. This patient was finally diagnosed as GSD Ia complicated with hepatic adenoma and combined with chronic hepatitis B, and received corn starch therapy immediately after GSD was suspected. After receiving corn starch therapy, the height and weight of the patient were increased, and the secondary sexual characteristics were developed, including beard, pubic hair and seminal emission. Unexpectedly, the liver adenomas were still increasing, and we did not find any cause to explain this phenomenon.

Conclusion: This patient was diagnosed as GSD Ia combined with chronic hepatitis B, who responded to corn starch intervention. For childhood patients with hypoglycaemia, hyperlipidemia, puberty delay and growth retardation, GSD should be considered. Gene sequencing is valuable for the quick identification of GSD subtypes.

Keywords: Chronic hepatitis B; G6PC gene; GSD Ia; Growth retardation.

Fig. 1

The Gd-EOB-DTPA tumor specific detection showed: glycogen accumulation. Arrow shows the largest nodule. a MRI (Gd-EOB-DTPA) examined on base line (2016.11.11 at presentation), the max size of nodules was 23 mm. b MRI (Gd-EOB-DTPA) examined 9 months after diagnosis of GSD I, the max size of nodules was 27 mm (c). MRI (Gd-EOB-DTPA) examined 12 months after diagnosis of GSD I, the max size of nodules was 34 mm. d MRI (Gd-EOB-DTPA) examined after radiofrequency ablation

Fig. 2

Pathological examination. a HBsAg staining of several cells was positive (400×). b HE staining of liver biopsy tissue (100×). c HE staining of liver biopsy tissue (400×). d PAS staining suggested a large deposition of glycogen in hepatocytes

Fig. 3

Mutational analysis in the patient pedigree. a The genotypes of G6PC gene for family members. Roman numerals indicate generations and Arabic numbers indicate individuals. Squares = males, circles = females. Affected individuals are denoted by solid symbols and unaffected individuals are denoted by open symbols. The index patient is indicated by an arrow. The two mutations were inherited from father and mother respectively. b Validation for the c.G648T of exon 5 by Sanger Sequencing. The red frame was mutation point