Glycogen storage disease type 1b (GSD1b) is a rare genetic disorder, resulting from mutations in the SLC37A4 gene located on chromosome 11q23.3. Although the SLC37A4 gene has been identified as the pathogenic gene for GSD1b, the complete variant spectrum of this gene remains to be fully elucidated. In this study, we present three patients diagnosed with GSD1b through genetic testing. We detected five variants of the SLC37A4 gene in these three patients, with three of these mutations (p. L382Pfs*15, p. G117fs*28, and p. T312Sfs*13) being novel variants not previously reported in the literature. We also present a literature review and general overview of the currently reported SLC37A4 gene variants. Our study expands the mutation spectrum of SLC37A4, which may help enable genetic testing to facilitate prompt diagnosis, appropriate intervention, and genetic counseling for affected families.

Glycogen storage disease (GSD) type 1a is an inherited autosomal recessive metabolic disease caused by a deficiency in glucose-6-phosphatase activity. The objectives of this research were to systematically review the published literature on the epidemiology of GSD 1a and to assess the performance of reported epidemiology measures in a simulation model. In this systematic literature review 2,539 record titles and abstracts were screened. Of these, only 11 studies contained relevant data on GSD 1a disease epidemiology. Reported disease frequency ranged from 0.085/100,000 to 10.3/100,000 newborns when considering all the GSD literature. When this was narrowed to GSD 1 and GSD 1a, the range was tightened to 0.25-3.02/100,000 and 0.085-4.9/100,000 newborns, respectively. Most of the identified studies counted the number of diagnoses in a defined period and related to the number of births in the same (Dx method) or different time period (DoB method). The simulation model results indicate that in most of the situations, the Dx method provides a closer estimate to the true disease incidence than the DoB method. Despite the scarcity of epidemiology data, the results of this systematic review strongly support that GSD 1a and its parent disease groups (GSD and GSD 1) are rare diseases.

Glycogen storage diseases (GSDs) with liver involvement are classified into types 0, I, III, IV, VI, IX and XI, depending on the affected enzyme. Hypoglycemia and hepatomegaly are hallmarks of disease, but muscular and renal tubular involvement, dyslipidemia and osteopenia can develop. Considering the paucity of literature available, herein we provide a narrative review of these latter forms of GSDs.
Diagnosis is based on clinical manifestations and laboratory test results, but molecular analysis is often necessary to distinguish the various forms, whose presentation can be similar. Compared to GSD type I and III, which are characterized by a more severe impact on metabolic and glycemic homeostasis, GSD type 0, VI, IX and XI are usually known to be responsive to the nutritional treatment for achieving a balanced metabolic homeostasis in the pediatric age. However, some patients can exhibit a more severe phenotype and an important progression of the liver and muscular disease. The effects of dietary adjustments in GSD type IV are encouraging, but data are limited.
Early diagnosis allows a good metabolic control, with improvement of quality of life and prognosis, therefore we underline the importance of building a proper knowledge among physicians about these rare conditions. Regular monitoring is necessary to restrain disease progression and complications.

Glycogen storage diseases (GSDs) are disorders of carbohydrate metabolism and hypoglycemia is their hallmark. Secondary diabetes with glycogen storage disease, which seems rather paradoxical, has been rarely reported. A 13-year-old girl previously diagnosed to have GSD 1a presented to the emergency with multiple episodes of vomiting and loss of consciousness. She had hyperglycemia, ketonuria, hyperlactatemia and metabolic acidosis, suggestive of diabetic ketosis with acidosis possibly contributed by both high serum lactate and serum ketones. Her glycated hemoglobin was high, with detectable serum insulin levels, which suggested secondary diabetes in the background of GSD Ia. Her management posed a therapeutic challenge. She was managed with insulin and achieved good glycemic control. We wish to conclude that GSD may rarely lead to secondary diabetes as a complication and the management is complex owing to the nature of the disease. Insulin remains the mainstay of the treatment.

BACKGROUND: Glycogen storage disease type IA (GSD IA) is an inherited disorder of glycogen metabolism characterized by fasting hypoglycemia, hyperuricemia, and hyperlipidemia including hypertriglyceridemia (HTG). Patients have a higher risk of developing acute pancreatitis (AP) because of HTG. AP is a potentially life-threatening disease with a wide spectrum severity. Nevertheless, almost no reports exist on GSD IA-induced AP in adult patients.
UNASSIGNED: A 23-year-old male patient with GSD 1A is presented, who developed moderate severe AP due to HTG.
UNASSIGNED: The GSD 1A genetic background of this patient was confirmed by Sanger sequencing. Laboratory tests, along with abdominal enhanced-computed tomography, were used for the diagnosis of HTG and AP.
METHODS: This patient was transferred to the intensive care unit and treated by reducing HTG, suppressing gastric acid, inhibiting trypsin activity, and relieving hyperuricemia and gout.
RESULTS: Fifteen days after hospital admission, the patient had no complaints about abdominal pain and distention. Follow-up of laboratory tests displayed almost normal values. Reexamination by computed tomography exhibited a reduction in peripancreatic necrotic fluid collection compared with the initial stage.
CONCLUSIONS: Fast and long-term reduction of triglycerides along with management of AP proved effective in relieving suffering of an adult GSD IA-patient and improving prognosis. Thus, therapeutic approaches have to be renewed and standardized to cope with all complications, especially AP, and enable a better outcome so that patients can master the disease.

Glycogen storage diseases (GSDs) with liver involvement are complex disorders with similar manifestations. Currently, the main diagnostic methods such as tissue diagnosis, either histopathology or enzyme assay, are invasive. Meanwhile, GSDs are diseases with significant genetic heterogeneity, and gene-sequencing methods can be more useful. This systematic review aims to review the literature to assess the value of massively parallel sequencing in the diagnosis of GSDs on patients with previously undiagnosed hepatic involvement.
Relevant studies identified in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science Core Collection databases up to July 2019 with no time and language restrictions. Publications were included in the review if they analyzed GSDs with hepatic involvement (GSD I, GSD III, GSD IV, GSD VI, GSD IX), using targeted gene sequencing (TGS) or exome sequencing (ES).
Eleven studies were included in this systematic review. ES demonstrated a 93% diagnostic yield. These methods correctly distinguished all types of pathogenic variants. The diagnostic yield of the TGS method was around 79.7%.
According to our results, TGS analysis can be considered as the first-line diagnostic method with valuable results and ES can be used to diagnose complex cases of GSD with liver involvement. Overall, these molecular methods are considered as accurate diagnostic tools, which expedite correct diagnosis and treatment with significant cost-effectiveness by reducing unnecessary and inaccurate tests.
CRD42020139931. Registered 8 January 2020.

An association between granulocyte colony-stimulating factor therapy (G-CSFT) in patients with glycogen storage disease type Ib (GSDIb) and the development of giant cell lesions of the maxillofacial complex has emerged. We have reported, to the best of our knowledge, the fourth case of giant cell granuloma (GCG) in a patient with GSDIb undergoing G-CSFT. GSDIb can present with hypoglycemia, hypertriglyceridemia, and neutropenia. G-CSFT has often been used in the treatment of recurrent infections or sepsis caused by neutropenia and to treat inflammatory bowel disease and diarrhea. The current reported data are lacking in both the association and the potential causation of G-CSFT and the development of giant cell tumors. Given the prevalence of GSDIb and its therapy, oral and maxillofacial surgeons should be aware of the tumorigenic potential of G-CSFT in patients with GSDIb. In the present report, we have described the case of a 17-year-old patient with GSDIb undergoing GCSFT who presented with a peripheral and central GCG. She was treated but presented again 13 months later with concerns for a new primary lesion. We have also discussed GSDIb, G-CSFT, and the current data, highlighting the association between G-CSFT for GSDIb, the potential mechanism of GCG development, the use of adjuvant therapy, and the need for close follow-up of this population. The purpose of the present case report is to highlight the presentation, management, and follow-up of giant cell lesions in patients with GSDIb treated with G-CSFT.

Cornstarch has been the primary treatment for glycogen storage disease type Ia (GSD Ia) for over 35 years. When cornstarch was first described as a treatment, few people survived beyond early childhood. As the prognosis for this population has improved, the need to ensure appropriate cornstarch dosing for different age groups has become imperative. Records from 115 patients (10-62 years of age) with GSD Ia evaluated at our center between 2015 and 2017 were reviewed. Data collected included weight, age, genetic mutation, amount and frequency of cornstarch doses, body mass index, gender, 24-hour glucose and lactate concentrations, and biochemical markers of metabolic control. The data demonstrate that adult treatment needs vary greatly from younger age groups, and the required cornstarch support decreases with age (P < .001). The required number of doses, however, did not change with a mean of six doses (range 4-8) daily in all age groups. General laboratory findings across time demonstrate that significantly reducing the amount of starch required to maintain euglycemia with aging can be done without sacrificing metabolic control. Carbohydrate requirements decrease with aging, and older patients were found to require less cornstarch. Failure to lower the cornstarch doses contributes to over-treatment in adults with GSD Ia. Not only does this lead to worsening hepatomegaly and excessive weight gain, but over-treatment contributes to relative hyperinsulinism and rebound hypoglycemia. This knowledge is essential in designing nutritional therapies for the aging GSD population.

Glycogen storage disease type I (GSD I) is a relatively rare metabolic disease with variable clinical intensity. It is caused by deficient activity of the glucose 6-phosphatase enzyme (GSD Ia) or a deficiency in the microsomal transport proteins for glucose 6-phosphate (GSD Ib). We searched the most recent English literature (1997-2017) regarding any article with the key word of \"glycogen storage disease type I\" in PubMed, Science Direct, Scopus, EMBASE, and Google Scholar. We will present all of the published articles about the molecular genetic characteristics and old-to-new diagnostic methods used to identify GSD I in regard of methodology, advantages and disadvantages. Diagnosis of GSD type I and its variants is challenging because it is a genetically heterogeneous disorder. Many molecular methods have been used to diagnose GSD I most of which have been based on mutation detection. Therefore, we discuss complete aspects of all of the molecular diagnostic tests, which have been used in GSD type I so far. With the advent of high throughput advanced molecular tests, molecular diagnosis is going to be an important platform for the diagnosis of storage and metabolic diseases such as GSD type I. Next-generation sequencing, in combination with the biochemical tests and clinical signs and symptoms create an accurate, reliable and feasible method. It can overcome the difficulties by the diagnosis of diseases with broad clinical and genetic heterogeneity.

A young female with recurrent tophaceous gout and infertility presented to our clinic. On clinical evaluation, hypoglycaemia, hypertriglyceridaemia, lactic acidosis, and hepatomegaly were noted. Targeted gene sequencing revealed a novel composite heterozygous c.190G>T/c.508C>T mutation in the G6PC gene of the patient, leading to a diagnosis of glycogen storage disease type Ia. Her father possessed a heterozygous c.190G>T mutation, and her mother possessed a heterozygous c.508C>T mutation. A search of the previous literature revealed 16 reported cases of glycogen storage disease type Ia with gout. Here, we describe a female patient with gout, review previous cases, and discuss the mechanisms of gout and hyperuricaemia in glycogen storage disease type Ia.