ABC | Volume 114, Nº4, Suplement, April 2020

Case Report Ballavenuto et al. Glycogen Storage Disease Type I: Report of two cases Arq Bras Cardiol 2020; 114(4Suppl.1):23-26 of apolipoproteins AI, AII are reduced; in addition, the concentrations of apolipoproteins CIII, B and E are elevated. An increase is observed not only in the number of VLDL and LDL particles, as becomes evident from the elevated apoB levels, but also in their size, due to the triglycerides accumulation in these fractions. 6-8 Bernier et al.9 demonstrated that the overall prevalence of hypercholesterolemia (31%) and hypertriglyceridemia (67%) are higher in GSDIa than in GSD-III patients. In adult populations, the biochemical abnormalities tend to attenuate, unlike hyperlipidemia, which persists in GSDIa, although with no higher related risk of atherosclerosis. 9 In the cases reported, the concentrations of triglycerides were considerably elevated since childhood, with high cholesterolemia as well, but in lower proportions, thus evolving until adolescence. It is possible to question whether, over time, hypoglycemia would tend to improve due to decreased metabolic rates in the body and to the influence of female sexual hormones, in addition to nutritional readaptation. Lipoprotein electrophoresis, performed in our patients, showed an increase in the pre-beta fraction in both of them. However, in the youngest patient, who had a more altered lipid profile, due to more severe hypertriglyceridemia, the electrophoresis test also exhibited a decrease in the alpha fraction. The European Study on Glycogen Storage Disease Type I (ESGSD I) recommends follow-up and routine laboratory tests (including lipid profiles), according with the patient’s age: age 0–3 years every 2 months; 3–20 years every 3 months; adults every 6months, as well as monitoring of cardiovascular diseases. 7 In this context, triglyceride concentration is considered the most useful parameter for chronic metabolic control with advanced age, in the presence of hypoglycemia, due to considerable improvements in serum levels of lactate and uric acid. 10 Regarding the research for subclinical atherosclerosis, since none of the patients had manifested atherosclerosis, a carotid Doppler ultrasound was performed, which revealed no alterations. However, healthy patients and of the same age, showed lower intimal thickness when compared to GSDI patients. 11 In a cohort of 28 patients with GSD I and 23 control subjects, Bernie et al. 9 compared carotid intima media thickness (cIMT) and mean augmentation index measured by radial artery tonometry. A greater cIMT value was found in the GSD cohort than in the control group, p < 0.02, adjusted for age, sex, and BMI (body mass index), in addition to mean augmentation index measured by radial artery tonometry, which was also higher in the GSD cohort (6.4% ± 14.0%) than in the control group (2.4% ± 8.7%) (p < 0.001). 8 These data suggest that GSDIa may be associated with major arterial dysfunction and increased risk for cardiovascular disease. On the other hand, there would be a possible cardiovascular protection, with decreased platelet adherence and, therefore, prolonged bleeding time, leading to lower risk of atherothrombosis. Detoxification of free radicals seems to be the leading protection factor for cellular membrane integrity, because it enhances NADPH2 production and activates the system of free radical detoxification. 1 Since their childhood, our patients had high triglycerides, which would correspond to a polygenic defect, with greater VLDL synthesis, followed or not by failure to metabolize it by lipoprotein lipase. 8 Later, in the 10 to 14 age range, both presented a proportional increase in cholesterol and triglycerides levels, usually greater than 300 mg/dL. This lipid profile, similar to Fredrickson phenotype III, would be the result of changes in apo E and/or due to a failure to metabolize IDL (intermediate density lipoproteins). 4 The GSPIa lipid profile usually suffers expressive changes, especially in relation to hypertriglyceridemia, with pancreatitis and hepatic adenomas being two of the major complications. 7 Regarding the treatment, in addition to specific dietary measures, the use of statins and fibrates would be indicated, for a better control of dyslipidemia, reduction of cardiovascular risk and prevention of pancreatitis. 7 Dietary management is traditionally based on the provision of exogenous carbohydrate to compensate for defective gluconeogenesis and achieve normoglicemia. Thus, frequent meals, continuous overnight enteral feeding and the administration of uncooked cornstarch are indicated. 12 The treatment also includes the use of fibrates as a way to prevent pancreatitis, sodium bicarbonate and xanthine oxidase inhibitors to treat metabolic acidosis and hyperuricemia, respectively. 7 Both patients have not presented renal alterations so far, which may be attributed to early dietetic treatment. 2 If hypoglycemia can be prevented, as mentioned before, the clinical and biochemical abnormalities, in most patients, tend to improve. 2 Nevertheless, hyperlipidemia tends to persist, although no greater risk of atherosclerosis has been observed so far. Since its introduction, the phenotype of G6PD deficient individuals has changed frommortality to morbidity, and the focus of attention has moved to the prevention of long-term complications, such as the possible consequences of severe dyslipidemia, among others. 12-14 Table 2 – Lipoprotein electrophoresis of patients Dosage Results (%) Reference (%) Patient 2 Paciente 2 Alpha lipoprotein 28.6 17.8 23-46 Pre-beta lipoprotein 36 36.8 3-18 Beta-lipoprotein 35.4 45.4 42-63 Lipoprotein (a) (Lp(a)) 0 0 25