By Laurie Tsilianidis, MD, and Carrie Gonzales, RD, CSP, LD
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Until the early 1970s, the most severe and well-known form of hepatic glycogen storage disease (GSD) was almost always fatal, marked by extreme failure to thrive, life-threatening hypoglycemia and acidosis. Today, infants and children diagnosed with this form of GSD (Type I, or von Gierke disease) or other GSD types can expect to live full, healthy lives with no limitations from their disease.
The primary reason for the turnaround was the discovery in 1971 that cornstarch was an effective therapy for hepatic forms of GSD, a heterogeneous group of inherited metabolic disorders characterized by defective glycogen utilization or synthesis. Though each form of GSD is distinct in presentation (Table 1), all forms manifest as fasting hypoglycemia and metabolic acidosis if untreated.
Uncooked cornstarch taken by mouth is digested slowly, which helps keep blood sugar levels normal for extended time periods. Refinements in the precise dosing and timing of cornstarch administration over recent decades have helped GSD specialists go beyond keeping patients alive to allow them to live normal lives.
Cleveland Clinic Children’s is among a very small number of centers worldwide dedicated to providing comprehensive clinical care to patients with GSD and increasing knowledge of this rare group of diseases through research. Since the initiation of our GSD Program in December 2012, children and families from all over the country have traveled to Cleveland Clinic Children’s to receive expert care from our specialized multidisciplinary team (Figure 1).
Incidence. The overall incidence of GSD is estimated to be 1 in 100,000 births. Mild forms of GSD are likely underdiagnosed.
Diagnosis. Definitive diagnosis of GSD previously required a liver biopsy and assay of enzyme activity, but now all types can be diagnosed noninvasively. When a particular type of GSD is suspected based on characteristic clinical and biochemical abnormalities, mutation analysis is recommended to confirm the diagnosis.
Treatment objective. In all types of GSD, the goal of treatment is to maintain normal blood glucose levels and minimize the metabolic derangements associated with hypoglycemia.
Treatment overview. The mainstay of therapy for all types of GSD is uncooked cornstarch. Patients mix the starch in water or other sugar-free liquid and drink it at specified intervals throughout the day. Uncooked cornstarch is a slowly digested dietary source of glucose that maintains blood glucose levels in the normal range for hours longer than other carbohydrate sources can.
The exact dose and interval that maintain normal blood glucose levels will vary by type of GSD, patient age and individual factors. Patients with GSD Type I require the highest doses and most frequent dosing because the enzyme that is deficient in these patients is also required in the gluconeogenic pathway.
For this reason, protein or other nonglucose substrate cannot be used to decrease the amount of cornstarch required. For the same reason, galactose and fructose are monosaccharides that cannot be utilized by patients with GSD Type I. Sucrose, fructose and lactose are strictly avoided to prevent over storage in the liver.
Our unique program at Cleveland Clinic Children’s offers patients with GSD a comprehensive approach to assess and optimize metabolic control by tailoring therapy to the individual.
Patients are admitted to our program for a stay ranging from one night to more than a week. During the stay, the patient undergoes a thorough metabolic evaluation in which blood glucose and lactate concentrations are assessed hourly as the patient receives his or her current treatment regimen or a regimen that has been empirically adjusted.
All data collected during the hospitalization are used to adjust therapy to the exact regimen that will keep the individual’s blood glucose normal while preventing metabolic acidosis and other hypoglycemia-induced derangements. Patients also undergo screening laboratory studies, liver ultrasound and other tests as appropriate to assess for long-term complications of GSD.
Our team includes dietitians and physicians specializing in endocrinology, critical care, gastroenterology and genetics. We work together to address every issue related to the patient’s condition.
The prognosis for all types of GSD is excellent with appropriate treatment. Tailoring therapy to the individual can achieve excellent metabolic control. Virtually every long-term complication of GSD has been associated with metabolic control, and ameliorating the metabolic derangements from hypoglycemia can prevent morbidity.
Patients with GSD can expect to grow normally throughout childhood and participate in activities without any limitations. Long-term complications, once believed to be universal in the more severe forms of GSD, can be avoided with good metabolic control and near-normalization of laboratory tests. Liver transplantation is no longer routinely recommended for any type of GSD.
Ms. Gonzales, a pediatric nutrition specialist with an interest in metabolic disorders, is a key member of the Glycogen Storage Disease Program team. She can be reached at 216.445.1614 or gonzalc2@ccf.org.
Dr. Tsilianidis is Director of the Glycogen Storage Disease Program in the Center for Pediatric and Adolescent Endocrinology. She can be reached at 216.445.2082 or tsilial@ccf.org.
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