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

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.

Computed Tomography and Magnetic Resonance Imaging Features of Primary and Secondary Hepatic Glycogenosis.

Glycogen storage disease type I and glycogenic hepatopathy are the most common type of primary and secondary hepatic glycogenosis, with presenting common radiological features of hepatomegaly, hepatic signal, or density change. Beyond that, glycogen storage disease type I shows hepatocellular adenomas or fatty liver, while glycogenic hepatopathy does not.

Muscle Ultrasound in Patients with Glycogen Storage Disease Types I and III.

In glycogen storage diseases (GSDs), improved longevity has resulted in the need for neuromuscular surveillance. In 12 children and 14 adults with the "hepatic" (GSD-I) and "myopathic" (GSD-III) phenotypes, we cross-sectionally assessed muscle ultrasound density (MUD) and muscle force. Children with both "hepatic" and "myopathic" GSD phenotypes had elevated MUD values (MUD Z-scores: GSD-I > 2.5 SD vs. GSD-III > 1 SD, p < 0.05) and muscle weakness (GSD-I muscle force; p < 0.05) of myopathic distribution. In "hepatic" GSD-I adults, MUD stabilized (GSD-I adults vs. GSD-I children, not significant), concurring with moderate muscle weakness (GSD-I adults vs. healthy matched pairs, p < 0.05). In "myopathic" GSD-III adults, MUD increased with age (MUD-GSD III vs. age: r = 0.71-0.83, GSD-III adults > GSD-III children, p < 0.05), concurring with pronounced muscle weakness (GSD-III adults vs. GSD-I adults, p < 0.05) of myopathic distribution. Children with "hepatic" and "myopathic" GSD phenotypes were both found to have myopathy. Myopathy stabilizes in "hepatic" GSD-I adults, whereas it progresses in "myopathic" GSD-III adults. Muscle ultrasonography provides an excellent, non-invasive tool for neuromuscular surveillance per GSD phenotype.

FDG PET/CT in Type I Glycogen Storage Disease.

Type I glycogen storage disease (GSD) is a rare autosomal recessive disorder caused by glucose-6-phosphatase deficiency. We report herein the particular pattern provided by FDG PET imaging in a 33-year-old patient with type Ib GSD. PET images yielded evidence of a pulmonary infectious focus as well as of: (1) a dramatically enlarged liver leading to a high global FDG uptake, (2) increased bone marrow activity, (3) splenomegalia leading to a high global spleen uptake, (4) a diffuse enhancement in muscle FDG uptake.

[Cardiovascular risk profile of patients with glycogen storage disease type I].

OBJECTIVE: To investigate the cardiovascular risk profile in patients with glycogen storage disease (GSD) type I. METHOD: The clinical information of 62 patients with GSD type I who admitted to Peking Union Medical Hospital were reviewed and the cardiovascular risk profile was analyzed. RESULTS: The age of the patient cohort was (8.4 ± 6.9) years and the ratio of male vs. female was 36:26. The median disease duration was (6.7 ± 6.2) years and treatment duration was (38.3 ± 35.2) months. The rate of abnormal change in electrocardiogram and echocardiography was 17.7% and 24.2%, respectively. The serum concentration of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and uric acid in patient before and after treatment were (6.18 ± 2.47) mmol/L vs. (5.61 ± 1.84) mmol/L (P = 0.020), (11.17 ± 9.85) mmol/L vs. (6.81 ± 5.97) mmol/L (P = 0.010), (2.55 ± 1.27) mmol/L vs. (2.78 ± 1.07) mmol/L (P = 0.617), (0.98 ± 0.37) mmol/L vs. (0.96 ± 0.23) mmol/L (P = 0.005), (526.53 ± 127.09) µmol/L vs. (490.78 ± 129.79) µmol/L (P = 0.977), respectively. The high-sensitivity C-reactive protein levels tended to be higher after therapy compared before treatment (2.33 ± 3.30) mg/L vs. (3.35 ± 3.39) mg/L, P = 0.431. CONCLUSION: Patients with GSD I are associated with an increased risk for cardiovascular disease.

Acoustic accessibility investigation for ultrasound mediated treatment of glycogen storage disease type Ia patients.

Glycogen storage disease type Ia (GSDIa) is caused by an inherited defect in the glucose-6-phosphatase gene. The recent advent of targeted ultrasound-mediated delivery (USMD) of plasmid DNA (pDNA) to the liver in conjunction with microbubbles may provide an alternative treatment option. This study focuses on determining the acoustically accessible liver volume in GSDIa patients using transducer models of various geometries with an image-based geometry-driven approach. Results show that transducers with longer focal lengths and smaller apertures (up to an f/number of 2) are able to access larger liver volumes in GSDIa patients while still being capable of delivering the required ultrasound dose in situ (2.5 MPa peak negative pressure at the focus). With sufficiently large acoustic windows and the ability to use glucose to easily assess efficacy, GSD appears to be a good model for testing USMD as proof of principle as a potential therapy for liver applications in general.

Contrast-enhanced ultrasonography in patients with glycogen storage disease type Ia and adenomas.

OBJECTIVE: The purpose of this series was to evaluate the value of contrast-enhanced ultrasonography (CEUS) in the characterization of focal liver lesions (FLLs) in patients with glycogen storage diseases (GSDs). METHODS: Contrast-enhanced ultrasonographic data obtained for characterization of 8 FLLs (size, 0.9-10.2 cm) in 2 patients with GSD type Ia (GSD-Ia) and lesion growth or recurrent abdominal pain were reviewed and compared with computed tomographic (CT) and magnetic resonance imaging (MRI) data. After total and left hepatectomy, pathologic examination confirmed benign adenomas in 6 of the evaluated lesions. Follow-up confirmed benignity in the 2 remaining lesions. RESULTS: In all FLLs, CEUS showed marked hypervascularity in the early arterial phase. Centripetal filling was shown in only 1 lesion, and diffuse enhancement without any clear direction was shown in all other lesions. During the portal and late phases, 6 of the 8 lesions showed sustained enhancement, including 2 lesions that appeared heterogeneous during all phases of CT and MRI. In an aspect of 1 of these 6 large adenomas, late wash-out could be explained by sinusoid compression. The other 2 adenomas showed moderate wash-out but remained homogeneous. CONCLUSIONS: Focal liver lesions found in patients with GSD-Ia have similar patterns on CEUS compared with incidental adenomas. Global or partial hypoenhancement observed in the late phase did not indicate a transition to hepatocellular carcinoma but may have been related to ischemia.

Dental findings in a child with glycogen storage disease type IA.

Glycogen storage disease type I, also known von Gierke's disease, is a rare, severe autosomal recessive disorder due to a defect in liver, kidney, and intestinal mucosa. The existence of delayed development of the dentition, increased incidence of dental caries, taurodontism, and prolonged bleeding following dental procedures should lead clinicians to consider type I glycogen storage disease. A 10-year-old boy with glycogen storage disease type I whose condition was first diagnosed when he was 4 years of age, was referred to the clinic for multiple caries and evaluation of delayed tooth eruption. On physical examination, the patient was cooperative, with short stature, protuberant abdomen, and growth retardation. Laboratory findings indicated that blood levels of pyruvate, triglycerate, uric acid, and cholesterol were elevated. Intraorally delayed mixed dentition was evident, and approximal caries were found in teeth 55, 54, 52, 51, 61, 62, 65, 74, 84, and 85. The most significant radiographic finding was consistent with taurodontism of the molar teeth. Lateral and posteroanterior cephalometric films showed that dimensions of the craniofacial complex were strongly reduced. Evaluation of the patient's dental age was approximately 6 years.

Renal sonographic findings of type I glycogen storage disease in infancy and early childhood.

BACKGROUND: Type I glycogen storage disease (GSD-I) is an inherited disorder affecting glycogenolysis and gluconeogenesis. The characteristic manifestations are hepatomegaly, hypoglycemia, hyperlacticacidemia, hyperuricemia, and hyperlipidemia. Renal disease is regarded as a long-term complication and is reported mainly in older patients. OBJECTIVE: We report the renal manifestations and renal ultrasonographic findings of GSD-I in infancy and early childhood in order to assess the role of renal sonography in the diagnosis of GSD-I. MATERIALS AND METHODS: We retrospectively reviewed our hospital's database for patients with GSD-I from January 1993 to September 2004. The records of five patients were reviewed for this study. These five patients were diagnosed when they were younger than 3 years old. Data extracted from the charts included the initial extrarenal and renal manifestations, laboratory data, and imaging studies. We analyzed the indications for, and results of, renal sonography. RESULTS: In addition to the clinical presentations and laboratory abnormalities, all five children had nephromegaly and increased echogenicity on ultrasonography on their first visit, although only a minor degree of tubular dysfunction was noted clinically. Three of these five patients had nephrocalcinosis or renal stones or both. CONCLUSION: Hyperechoic large kidneys, nephrocalcinosis, and renal stones are common in GSD-I. They can be present in early infancy. Abnormalities on renal sonography might suggest GSD-I in a patient with suspected inborn errors of metabolism.

Bone mineral density and markers of bone turnover in patients with glycogen storage disease types I, III and IX.

Patients with glycogen storage disease (GSD) types I, III and IX show reduced bone mineral content, but there is scarce data on new serum and urine markers of bone turnover or their relationship to bone densitometry. Six GSD I, four GSD III and four GSD IX patients underwent bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry. Free pyridinoline (fPYD):creatinine and free deoxypyridinoline (fDPD):creatinine ratios were analysed on random urines. Procollagen type I C-terminal propeptide, procollagen type I N-terminal propeptide (PINP), carboxyterminal telopeptide of type I collagen and bone-specific alkaline phosphatase were analysed in serum. Some GSD I and GSD III patients had low or very low BMD. There was no difference in total body BMD z-score between the GSD types after adjusting for height (p=0.110). Bone marker analysis showed no consistent pattern. Urine fPYD:creatinine ratio was raised in four GSD I and two GSD III patients, while serum PINP was inappropriately low in some of these patients. There was no clear correlation between any markers of bone destruction and total body z-score, but the patient with the lowest total body z-score showed the highest concentrations of both urinary fPYD:creatinine and fDPD:creatinine ratios. We conclude that some GSD I and GSD III patients have very low bone mineral density. There is no correlation between mineral density and bone markers in GSD patients. The inappropriately low concentration of PINP in association with the raised urinary fPYD:creatinine and fDPD:creatinine ratios seen in two GSD I patients reflect uncoupling of bone turnover. All these findings taken together suggest that some GSD I and GSD III patients may be at an increased risk of osteoporosis.

Acute myelogenous leukemia and glycogen storage disease 1b.

Glycogen storage disease 1b (GSD 1b) is caused by a deficiency of glucose-6-phosphate translocase and the intracellular accumulation of glycogen. The disease presents with failure to thrive, hepatomegaly, hypoglycemia, lactic acidosis, as well as neutropenia causing increased susceptibility to pyogenic infections. We present a case of a young woman with GSD 1b who developed acute myelogenous leukemia while on long-term granulocyte colony-stimulating factor therapy. The presence of two rare diseases in a single patient raises suspicion that GSD 1b and acute myelogenous leukemia are linked. Surveillance for acute myelogenous leukemia should become part of the long-term follow-up for GSD 1b.

Monitoring the correction of glycogen storage disease type 1a in a mouse model using [(18)F]FDG and a dedicated animal scanner.

Monitoring gene therapy of glycogen storage disease type 1a in a mouse model was achieved using [(18)F]FDG and a dedicated animal scanner. The G6Pase knockout (KO) mice were compared to the same mice after infusion with a recombinant adenovirus containing the murine G6Pase gene (Ad-mG6Pase). Serial images of the same mouse before and after therapy were obtained and compared with wild-type (WT) mice of the same strain to determine the uptake and retention of [(18)F]FDG in the liver. Image data were acquired from heart, blood pool and liver for twenty minutes after injection of [(18)F]FDG. The retention of [(18)F]FDG was lower for the WT mice compared to the KO mice. The mice treated with adenovirus-mediated gene therapy had retention similar to that found in age-matched WT mice. These studies show that FDG can be used to monitor the G6Pase concentration in liver of WT mice as compared to G6Pase KO mice. In these mice, gene therapy returned the liver function to that found in age matched WT controls as measured by the FDG kinetics in the liver compared to that found in age matched wild type controls.

Sonographic findings in type I glycogen storage disease.

PURPOSE: The aim of this study was to document the sonographic appearance and dimensions of the liver and spleen in patients affected by type I glycogen storage disease and to correlate those findings with laboratory data to evaluate the potential role of sonography in diagnosing that disease. METHODS: Fourteen patients (age range, 3-26 years; 10 patients younger than 18 years) with type I glycogen storage disease proved by liver biopsy were studied prospectively with gray-scale sonography, color Doppler sonography, and spectral analysis. The liver, kidneys, spleen, portal system, hepatic veins, and hepatic arteries were evaluated. Laboratory data were correlated with sonographic findings. RESULTS: In 13 (93%), of 14 patients, the liver was enlarged, and in 11 patients (79%), hepatic echogenicity was increased. In 9 patients (64%), both kidneys were enlarged, and in 6 cases (43%), the spleen was enlarged. In all patients, flow in the portal, splenic, and superior mesenteric veins was hepatopetal, and flow in the hepatic veins was triphasic. In 5 patients (36%), both triglyceride and total cholesterol levels were higher than normal. No focal hepatic lesions were identified. Analysis found no significant association between sonographic findings and laboratory data. CONCLUSIONS: The most frequent sonographic findings in patients with type I glycogen storage disease were hepatomegaly, increased hepatic echogenicity, and enlarged kidneys. Sonography may help in the diagnosis of type I glycogen storage disease, but a liver biopsy is required for a definitive diagnosis.

The prevalence of polycystic ovaries in the hepatic glycogen storage diseases: its association with hyperinsulinism.

OBJECTIVE: There has been much debate concerning the relative contribution of insulin resistance to the development of polycystic ovaries (PCO). We therefore aimed to assess ovarian morphology and insulin/androgen status in females with the hepatic glycogen storage diseases types Ia (GSD-Ia) and III (GSD-III), disorders associated with abnormalities of insulin secretion. DESIGN: A cross-sectional study of ovarian ultrasonography, oral glucose tolerance tests (oGTTs) and single measurements of gonadotrophins and androgens were performed. PATIENTS: Twenty-seven patients were evaluated: 13 with GSD-Ia, median age 11.2 years (range, 3.3-26.7) and 14 with GSD-III, aged 13.2 years (4.2-31.3). None had clinical signs of hyperandrogenism and only two of the 13 adults (15%) had menstrual irregularities. They were compared to 9 normal adult female controls, aged 21-28 years. MEASUREMENTS: Ovarian morphology and volume were measured. Blood glucose and plasma insulin concentrations were measured at the beginning and end of a 2-hour oGTT. Single measures of LH, FSH, testosterone, dehydroepiandrosterone sulphate, androstenedione, IGF-I and SHBG were made on samples taken at the beginning of the oGTT. RESULTS: In both GSD-Ia and III, all those older than 4.8 years of age had a polycystic ovarian appearance. Pre-pubertal GSD-Ia patients had lower basal and 2-hour blood glucose and plasma insulin concentrations than pre-pubertal GSD-III patients. In adults with GSD-Ia and GSD-III, although basal and 2-hour blood glucose concentrations did not differ, both basal and 2-hour plasma insulin concentrations were significantly higher than controls. Serum gonadotrophins, androgens, IGF-I and SHBG were mostly normal. CONCLUSIONS: A polycystic ovarian appearance is a common finding in patients with glycogen storage disease even before puberty. In GSD-III and adults with GSD-Ia, this ovarian appearance was associated with hyperinsulinism, suggesting an aetiological link, but this was not the case in pre-pubertal children with GDS-Ia. Inborn errors of carbohydrate metabolism may act as useful models for examining control mechanisms of ovarian physiology and development.