Two successful pregnancies in a woman with Glycogen Storage Disease (GSD) Type III

BACKGROUND: Glycogen Storage Disease (GSD) type III is an autosomal recessive disease due to deficiency in glycogen debranching enzyme, amylo-1,6-glucosidase, which can present two different phenotypes (IIIa and IIIb). GSD IIIa occurs more frequently (85%), causing liver disease and other complications including skeletal myopathy and hypertrophic cardiomyopathy, while GSD IIIb is a purely hepatic form (2). Women affected by GSD type III do not seem to have any issues with fertility (although polycystic ovary disease can invariably be demonstrated); the disease may significantly interfere with the physiological course of pregnancy in terms of mother’s and offspring’s health, although overall the outcome of pregnancy is good. Energy and glucose demands fall with age; because of the increased metabolic demand during pregnancy, females affected by GSD III are more predisposed to hypoglycemia (1), ketosis and lactic acidosis, with higher risk of intrauterine growth retardation and low birth weight (2), lower IQ (3) and increased susceptibility to type 2 diabetes in elder life (4). Patients with GSD IIIa, particularly if a cardiomyopathy pre-exists, should be monitored carefully to avoid a possible deterioration of cardiac function during pregnancy and again in post-partum period (2). CASE REPORT: We report the case of two successful pregnancies in a 39-year-old woman affected by GSD type IIIa, under follow up at our Metabolic Department. Second-born of three siblings (the younger also affected), she was suspected with GSD IIIa at 8 months of age (clinical findings of hypoglycemia and hepatomegaly) and the diagnosis was then confirmed by liver biopsy (residual enzymatic activity: 0-zero). After medical assisted procreation with intracytoplasmic sperm injection, respectively at the age of 32 and 38 years, she carried out two pregnancies under a strict metabolic, nutritional and cardiac monitoring. During both pregnancies she required frequent meals and the early introduction of regular assumption of uncooked cornstarch (UCCS, 1 g/Kg at bedtime) in her dietetic therapy (consisting of roughly 55% carbohydrate-complex rather than simple- and 26% protein), in order to maintain a good metabolic profile. In addition to obstetric and metabolic care, she was closely monitored also by our cardiologic team, showing stable parameters even for cardiac function. Transthoracic echocardiograms showed mild left-ventricular hypertrophic cardiomyopathy, with maximal wall thickness (MWT) of 12 mm and normal systolic function. In both labours, she maintained normoglycemia by using a dextrose iv infusion alone, stopped two hours after deliveries when she was able to start again a regular feeding. Both infants were delivered vaginally at term, with adequate weight/length/head circumference for gestational age. Re-bound hypoglycemia was not observed either in patient or in newborns, but she preferred bottle-feeding for her babies. No development of hepatic adenomas was observed during pregnancy/post-partum period. Now, six months after the second childbirth, an increased cardiac MWT (20 mm) with stable ejection fraction was observed, requiring a deepened evaluation (cardiac MRI to identify an eventual development of cardiac fibrosis). DISCUSSION: Adaptations in maternal metabolism during a normal pregnancy are designed to ensure an adequate supply of nutrients and energy to the foetus; women with GSD III may not be able to match glucose production with increasing energy demands in pregnancy. Adults with GSD III often don’t require additional feeds but metabolic evaluations during pregnancy have shown that nocturnal ketosis returns requiring late night and/or early morning cornflour supplements. Euglycemia needs to be maintained during pregnancy as lipolysis and ketosis increase the risk of fetal demise (1). Increased effort during labour can require an additional continue glucose supplementation, using a dextrose infusion and/or frequent meals with UCCS, with regular blood glucose testing. Cardiac disease in women with GSD III therefore has important implications in terms of management of pregnancy, pain relief, anaesthesia, fluid delivery, surgical intervention and the peri-partum period. Therefore females with GSD III in childbearing age should be counselled with regards to the potential impact of pregnancy on both their metabolic state and cardiac risk. CONCLUSION: This case strengthens the evidence that a careful and suitable management strongly concurs to positive outcomes in GSD III pregnancies. We can conclude that the course of pregnancy in patients affected by GSD III, in terms of mother’s and offspring’s health, can be optimal only taking into account some indispensable issues. References: (1) Bolton SD, Clark VA, Norman JE. Multidisciplinary management of an obstetric patient with glycogen storage disease type 3. Int J Obstet Anesth. 2012 Jan;21(1):86-9 (2) Ramachandran R, Wedatilake Y, Coats C, Walker F, Elliott P, Lee PJ, et al. Pregnancy and its management in women with GSD type III-a single centre experience. J Inherit Metab Dis. 2012 Mar;35(2):245-51. (3) Rizzo T, Metzger BE, Burns WJ, Burns K (1991) Correlations between antepartum maternal metabolism and child intelligence. N Engl J Med 325(13):911–916 (4) Petry CJ, Hales CN (2000) Long-term effects on offspring of intrauterine exposure to deficits in nutrition. Hum Reprod Update 6(6):578–586