Glycogen Storage Disease in A 4-year-old

Journal of Medical Case Reports

Case Presentation

A 4-year-old or 6-month-old Caucasian girl came to the pediatric clinic with a diagnosis of glycogen storage disease (GSD). Before being referred to the clinic, she had been receiving care from pediatric gastroenterologists. Her initial symptoms included experiencing chronic abdominal pain and constipation. During an abdominal examination, doctors found that the liver was slightly enlarged with a coarse texture. Moreover, initial tests showed elevated liver transaminases. As time progressed, she began experiencing liver-related symptoms such as itching and jaundice, but there were no further complications. Consequently, the doctors prescribed vitamin E and ursodeoxycholic acid as possible treatments for cholestasis.

Despite ongoing elevation in her liver transaminases, an evaluation of hepatic autoantibodies did not provide evidence of autoimmune liver disease. Wilson’s disease was also ruled out. Despite extensive efforts, the gastroenterologists were unable to make a definitive diagnosis during the follow-up period. Therefore, they decided to perform a liver biopsy due to the persistently elevated liver transaminases.

Liver Biopsy

Doctors used spectrophotometry to evaluate glycogenesis in the biopsy, revealing a preserved parenchymal structure with mostly enlarged hepatocytes. These hepatocytes exhibited round, uniform nuclei with occasional inclusions and expanded cytoplasm that ranged from clear to a wispy pink colour. They had well-defined borders. Periodic acid-Schiff (PAS) staining confirmed that the cytoplasmic inclusions were glycogen. Importantly, there were no signs of inflammation or fibrosis in the liver.

Following the biopsy, the patient was referred to the endocrinology and metabolic clinic with a confirmed diagnosis of GSD. This young girl was the third child in a family of three, and her parents were blood relatives. She was born via normal vaginal delivery (NVD) at 36 weeks of gestation, weighing 2600 g. This fell between the 5th and 10th percentiles. Early on, she was breastfed and tolerated it well.

At the time of referral to the clinic, her weight, height, and head circumference were measured at 14 kg (25th percentile), 100 cm (10th–25th percentile), and 49 cm (15th percentile), respectively. She had met all expected developmental milestones, exhibited age-appropriate motor development, attended school regularly, and achieved satisfactory results. Her medical and family history did not reveal any significant issues, and her psychosocial functioning was normal.


Upon physical examination, her liver was palpable, but the texture was not coarse. Additionally, she had a grade 1a goitre. Laboratory tests showed her haemoglobin (Hb) level to be 11.6 mg/dl, mean corpuscular volume (MCV) at 88 fl, aspartate transaminase (AST) at 96 U/l, alanine transaminase (ALT) at 88 U/l, alkaline phosphatase (ALP) at 745 U/l, creatinine (Cr) at 0.5 mg/dl, blood urea nitrogen (BUN) at 19 mg/dl, calcium (Ca) at 10.3 mg/dl, phosphorus at 5.6 mg/dl, ferritin at 24 μg/l, and thyroid stimulating hormone (TSH) at 1.3 m IU/l.

Given the diagnosis of GSD, the patient’s management involved dietary measures. Since the most common forms of GSD are type I and type III, the doctors recommended frequent feedings. They recommended a diet rich in complex carbohydrates, which included a corn starch supplement and lactose restriction.

A month later, follow-up laboratory tests were conducted, including AST, ALT, creatine phosphokinase (CPK), copper (Cu), prothrombin time (PT), International Normalized Ratio (INR), and ammonia.

After three months, doctors evaluated the patient again. She reported no particular issues, but her physical examination revealed hepatomegaly. Laboratory tests indicated an AST of 59 U/l, ALT of 86 U/l, CPK of 77 U/l, Cu of 59 μg/dl, PT of 12 seconds, INR of 1.1, and ammonia of 119.4 μg/dl. Furthermore, she was not adhering to the prescribed diet.

Regular Follow-Ups

Subsequently, she underwent regular monitoring every three months for a year. Unfortunately, despite diligent follow-ups, her condition did not improve. A slight enlargement of the liver was still palpable on physical examination. She had not adhered to the recommended diet. Her lipid profile remained within the normal range, but her liver transaminase levels were consistently elevated. Additionally, her vitamin D level was close to normal, and her thyroid stimulating hormone (TSH) level was normal as well. To rule out secondary causes such as hypothyroidism, doctors performed further evaluations.

After one year, her linear growth had not improved, and her weight and height measured 15 kg (10–25th percentile) and 101.5 cm (10–25th percentile), respectively. The physical examination still indicated a palpable liver and goitre. Laboratory tests revealed a triglyceride (TG) level of 127 mg/dl, high-density lipoprotein (HDL) of 39 mg/dl, low-density lipoprotein (LDL) of 87 mg/dl, total cholesterol (TC) of 144 mg/dl, TSH of 3.35 m IU/L, free T4 of 1.5 μg/dl, vitamin D of 29 ng/ml, Ca of 10 mg/dl, uric acid of 4.5 mg/dl, Cr of 0.6 mg/dl, lactate of 10.2 mg/dl, ferritin of 54 μg/l, AST of 94 U/l, and ALT of 86 U/l. In addition to her existing regimen, doctors further added vitamin D and vitamin B complexes. Moreover, they requested a liver ultrasound and further laboratory tests for her next appointment.

During the follow-up visit one month later, the patient’s mother reported that the patient had not been using corn starch. On physical examination, the liver was palpable, but doctors found no other abnormalities. Laboratory tests showed an AST of 60 U/l, ALT of 59 U/l, vitamin D of 70 ng/ml, and lactate of 4.3 mg/dl. The ultrasound report indicated glycogen accumulation in hepatocytes classified as a grade 2 fatty liver, with no adenoma detected. The liver size had increased to 120 mm, exhibiting a coarse and slightly increased echogenicity. The spleen size remained normal at 75 mm.

Continuous Monitoring

The doctors continued to monitor the patient for a year with 3-month follow-up visits, during which they assessed her lipid profile, AST, ALT, ALP, vitamin D, GH, IGF-1, and liver ultrasound. The laboratory results showed a TG of 135 mg/dl, HDL of 47 mg/dl, LDL of 129 mg/dl, TC of 175 mg/dl, AST of 63 U/l, ALT of 88 U/l, ALP of 682 U/l, vitamin D of 17 ng/ml, GH of 7.6 ng/ml, and IGF-1 of 118 ng/ml. The ultrasound report indicated that the size of the liver had grown to 130 mm, and subsequent follow-ups showed that it was continuing to increase.

Given her reported loss of appetite and non-adherence to the prescribed diet, doctors recommended nutritional counselling to provide a high-carbohydrate diet. Due to the increasing size of the liver, they also requested a gastroenterology consultation.

Throughout the third follow-up, the patient failed to adhere to her prescribed diet, resulting in an unfavourable growth status. Her weight and height were 19 kg (3rd–10th percentile) and 116 cm (10th percentile), respectively. On physical examination, her liver was palpable. Her laboratory tests revealed the following values: TG of 197 mg/dl, HDL of 37 mg/dl, LDL of 99 mg/dl, TC of 162 mg/dl, AST of 62 U/l, ALT of 79 U/l, ferritin of 31.3 μg/l, lactate of 9.6 mg/dl, BUN of 29 mg/dl, Cr of 0.6 mg/dl, and CPK of 88 U/l. The liver measured 143 mm in size. Doctors also noted an increase in the echo of the liver parenchyma in the liver ultrasound report.


After a month of nutritional counselling, the doctors incorporated calcium supplementation into the patient’s treatment plan. In response to the ineffectiveness of previous measures by the gastroenterologist, doctors requested a genetic analysis. Utilizing whole-exome sequencing (WES), the patient’s DNA was examined for various genes, uncovering a c.C412T (P.Q138x) mutation linked to a PHK enzyme defect. No reports of this mutation have been documented in the Human Gene Mutation Database® (HGMD®). Additionally, the American College of Medical Genetics and Genomics (ACMG) classified it as a variant of uncertain significance (VUS), signifying its rarity. This autosomal recessive mutation is characterized by a homozygous variant in exon 5 of chromosome 16.

Genetic testing aimed to accurately diagnose the patient’s specific type of GSD, as initial treatment was based on assumptions of GSD-I and GSD-III. However, GSD-IX treatment differs significantly. Confirming the GSD-IX diagnosis was crucial. Following the diagnosis, the patient was advised to follow a lactose-restricted diet with complex carbohydrates, avoid simple carbohydrates, and adhere to a high-protein diet (more than 2 g/kg/day) with low-fat content. After two and a half years post-GSD-IX diagnosis, the patient consistently followed the prescribed diet. Her weight and height were measured at 31 kg (25–50th percentile) and 136 cm (25–50th percentile), respectively. Laboratory tests indicated TG of 128 mg/dl, HDL of 33 mg/dl, LDL of 103 mg/dl, TC of 171 mg/dl, AST of 59 U/l, ALT of 69 U/l, vitamin D of 29 ng/ml, BUN of 29 mg/dl, and Cr of 0.6 mg/dl. She maintained regular school attendance with satisfactory academic performance.


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