Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Abstract

Disclaimer This practice resource is designed primarily as an educational resource for medical geneticists and other clinicians to help them provide quality medical services. Adherence to this practice resource is completely voluntary and does not necessarily assure a successful medical outcome. This practice resource should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinician should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. Clinicians are encouraged to document the reasons for the use of a particular procedure or test, whether or not it is in conformance with this practice resource. Clinicians also are advised to take notice of the date this practice resource was adopted, and to consider other medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures. Purpose: Glycogen storage disease (GSD) types VI and IX are rare diseases of variable clinical severity affecting primarily the liver. GSD VI is caused by deficient activity of hepatic glycogen phosphorylase, an enzyme encoded by the PYGL gene. GSD IX is caused by deficient activity of phosphorylase kinase (PhK), the enzyme subunits of which are encoded by various genes: ɑ (PHKA1, PHKA2), β (PHKB), ɣ (PHKG1, PHKG2), and δ (CALM1, CALM2, CALM3). Glycogen storage disease types VI and IX have a wide spectrum of clinical manifestations and often cannot be distinguished from each other, or from other liver GSDs, on clinical presentation alone. Individuals with GSDs VI and IX can present with hepatomegaly with elevated serum transaminases, ketotic hypoglycemia, hyperlipidemia, and poor growth. This guideline for the management of GSDs VI and IX was developed as an educational resource for health-care providers to facilitate prompt and accurate diagnosis and appropriate management of patients. Methods: A national group of experts in various aspects of GSDs VI and IX met to review the limited evidence base from the scientific literature and provided their expert opinions. Consensus was developed in each area of diagnosis, treatment, and management. Evidence bases for these rare disorders are largely based on expert opinion, particularly when targeted therapeutics that have to clear the US Food and Drug Administration (FDA) remain unavailable. Results: This management guideline specifically addresses evaluation and diagnosis across multiple organ systems involved in GSDs VI and IX. Conditions to consider in a differential diagnosis stemming from presenting features and diagnostic algorithms are discussed. Aspects of diagnostic evaluation and nutritional and medical management, including care coordination, genetic counseling, and prenatal dia...

Novel variants in Turkish patients with glycogen storage disease

“…In the same study, the incidence of c.1620 + 1G> A mutation was reported to be high. 16 However, this mutation was not detected in our patients.…”

Novel PYGL mutations in Chinese children leading to glycogen storage disease type VI: two case reports

“…GSD XI patients have malabsorption, renal abnormalities and acidosis. Among these different GSD types, GSD IXa is the type that is most similar to GSD VI because it results from deficiency of liver phosphorylase kinase, and phosphorylase kinase deficiency can itself lead to reduced liver phosphorylase activity [5].…”

“…Next-generation sequencing has been considered the preferred diagnostic method for GSD [5][6][7] because invasive liver biopsy can be avoided. We identified a novel homozygous gross deletion mutation (c.1621-258_2178-23del) of PYGL in patient 1 through WES.…”

Glycogen storage disease presenting as Cushing syndrome

“…Poorly controlled GSD with frequent hypoglycemia is associated with growth failure, and although excess weight gain in patients with GSD has been attributed to overfeeding, there are sparse data available regarding pretreatment weight trajectories. Growth failure in GSD correlates directly with serum cortisol levels, supporting the hypothesis that it may be due, at least in part, to hypercortisolism.…”