ABC | Volume 114, Nº4, Suplement, April 2020

Case Report Glycogen Storage Disease Type I (Von Gierke disease): Report of Two Cases with Severe Dyslipidemia Julia Maria Avelino Ballavenuto, 1 J éssica D´Ório Dantas de Oliveira, 1 Renato Jorge Alves 1 Irmandade da Santa Casa de Misericórdia de São Paulo, 1 São Paulo, SP - Brazil Introduction Glycogen storage diseases are a group of disorders caused by inherited errors of metabolism, resulting in abnormal glycogen concentration and/or structure in various body tissues. Nowadays, there are 14 types of glycogen storage disease, which are classified according to enzyme or transporter deficiency and to the different organ distribution of these defects. 1 In 1929, Edgar von Gierke described an increased deposition of glycogen in body tissues in the autopsy reports of young individuals with hemorrhagic manifestations. In 1952, Gerty and Cori analyzed liver biopsies of patients with similar symptoms, and observed a partial or total absence of glucose- 6-phosphatase (G6Pase) enzyme activity – this entity became known as Von Gierke disease. Nordlie et al., in studies carried out in the 70’s, also using liver biopsies, observed normal levels of G6Pase enzyme, but with decreased activity. 2 Thus, Glycogen Storage Disease Type I is characterized by G6Pase deficiency, a key enzyme in glycogen metabolism, which leads to the reduction in glycogenolysis and gluconeogenesis and, consequently, to hepatic accumulation of glucose-6- phosphate (G6P). 2 G6Pase is composed of a catalytic subunit and three translocases. GSDI is further divided into subtypes, depending on which enzyme is affected: subtype Ia (GSDIa), which corresponds to a deficiency in the catalytic unit; subtypes Ib, Ic and Id, which refer to deficiency of translocases 1, 2 and 3, respectively. Deficiency in the SP catalytic subunit has also been demonstrated, characterizing, thus, the subtype 1aSP. The diagnosis of the subtypes is confirmed by liver biopsy, with G6Pase activity being determined in tissue samples. 2 GSDIa is inherited as an autosomal recessive trait, representing about 80% of GSDI patients, with an incidence of 1/100,000 births worldwide. 3 It commonly manifests between the ages of 3 to 4 months, as a result of abnormal accumulation of glycogen in the liver, kidneys and intestine, by symptoms of hypoglycemia, hyperuricemia, lactic acidemia and severe dyslipidemia. Hypoglycemia usually manifests first as tremors, seizures, cyanosis and apnea and, in the long term, evolves to growth retardation. Physical examination shows non-painful hepatomegaly, with a smooth, palpable liver edge below the right costal margin, globe-like abdomen due to deposition of abdominal fat, often associated with short stature and a doll- like face. 3 As late complications, these patients may present an increase in kidney size (with or without worsening renal function), hepatic adenomas (with rare transformation into HCC) and neutropenia (a tendency to recurrent infections). 3-5 Hypertriglyceridemia, most prominent in GSDIa, is associated with long-term outcome morbidity, due to its relation with pancreatitis and hepatic adenomas. 6 Until the early 2000’s, liver biopsies were routinely perfomed to obtain tissue for enzyme analysis. Nowadays, the diagnosis is made based on mutation analysis of the G6Pase (glucose-6-phosphatase) and G6PT (glucose-6-phosphate translocase) genes by PCR-RFLP (Restriction Fragment Length Polymorphism), or by direct gene sequencing, associated with clinical and laboratory manifestations. Enzymatic studies are carried out if results remain inconclusive. 7 Patients with G6PD mutations may have the criteria for metabolic syndrome, especially hypertriglyceridemia, 8 reduced levels of high-density lipoproteins (HDL) and increased waist circumference. In this context, the monitoring of cardiovascular diseases in adult patients with GSDI would be justified. To a lesser extent, these patients may present with SAH (systemic arterial hypertension) as well, usually related to renal alterations, which may emerge from the second decade of life on. Focal segmental glomerulosclerosis, gout nephropathy and nephrocalcinosis are the likely etiologies of renal injury. Proteinuria is a frequent finding. However, renal alterations respond positively to dietary treatment, which explains why they are not common. 2 We report the cases of two patients with GSDIa, associated with severe and difficult to manage dyslipidemia, sisters and daughters of consanguineous parents (first cousins), with deceased father and mother with Hashimoto’s thyroiditis, without reports of other comorbidities. Case 1: Patient MCS, 24 years of age. During her first year of life, in 1994, she was hospitalized with a picture of fever, vomiting, glycosuria, tachypnea, metabolic acidosis and hypoglycemia. At that moment, an investigation of the case was initiated, which revealed high levels of total cholesterol and triglycerides, in addition to hyperuricemia and metabolic acidosis. The possibility of Glycogen Storage Disease type I was considered, being subsequently confirmed by liver biopsy and the clinical picture. Other pathologies related to inborn errors of metabolism were ruled out. At that time, laboratory tests showed: hemoglobin A1c of 4.2% and blood glucose 65mg/dL. Dietary treatment, with Mailing Address: Julia Maria Avelino Ballavenuto • Irmandade da Santa Casa de Misericórdia de São Paulo - Rua Dr. Cesário Mota Junior, 112. Postal Code 01009-972, Vila Buarque, Sã Paulo, SP – Brazil E-mail: ballavenuto@gmail.com Manuscript received January 16, 2019, revised manuscript April 03, 2019, accepted April 10, 2019 Keywords Glycogen Strage Disease Type 1/complications; Gluconeogenesis; Dyslipidemias; Hepatomegaly; Hypoglycemia; Glucose-6-Phosphate. DOI: https://doi.org/10.36660/abc.20190037 23