ppharmПедиатрическая фармакологияPediatric pharmacology1727-57762500-3089Издательство «ПедиатрЪ»10.15690/pf.v20i5.2646ppharm-2361Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWБолезнь накопления гликогена Ib типа: современное понимание патогенеза нейтропении и перспективы ее лечения эмпаглифлозиномGlycogen storage disease type Ib: modern understanding of the pathogenesis of neutropenia and prospects for its treatment with empagliflozinhttps://orcid.org/0000-0002-3697-4283СурковА. Н.SurkovAndrej N.

Сурков Андрей Николаевич, доктор медицинских наук, заведующий отделением гастроэнтерологии стационара для детей, заведующий отделом научных основ детской гастроэнтерологии, гепатологии и метаболических нарушений НИИ педиатрии и охраны здоровья детей НКЦ №2 ФГБНУ «РНЦХ им. акад. Б.В. Петровского» Минобрнауки России, профессор кафедры факультетской педиатрии педиатрического факультета ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России

117593, Москва, Литовский бульвар, д. 1А

тел.: +7 (916) 656-31-27

Andrej N. Surkov, MD, PhD

1А Litovskij boulevard, Moscow, 117593

tel.: +7 (916) 656-31-27

surkov@gastrockb.ruhttps://orcid.org/0000-0003-3987-8112БарановА. А.BaranovAleksandr A.

Баранов Александр Александрович, д.м.н., профессор, академик РАН

Москва

Aleksandr A. Baranov, MD, PhD, Professor, Academician of the RAS

Moscow

baranov@pediatr-russia.ruhttps://orcid.org/0000-0002-2209-7531Намазова-БарановаЛ. С.Namazova-BaranovaLejla S.

Намазова-Баранова Лейла Сеймуровна, д.м.н., профессор, академик РАН

Москва

Lejla S. Namazova-Baranova, MD, PhD, Professor, Academician of the RAS

Moscow

info@pediatr-russia.ruhttps://orcid.org/0000-0002-6837-9753АракелянА. Л.ArakelyanAnna L.

Аракелян Анна Левоновна

Москва

Anna L. Arakelyan, MD

Moscow

a.silonyan@mail.ruhttps://orcid.org/0000-0001-5549-857XБессоновЕ. Е.BessonovEvgenij E.

Бессонов Евгений Евгеньевич

Москва

Evgenij E. Bessonov, MD

Moscow

bessonov@gastrockb.ruhttps://orcid.org/0000-0001-6614-6115ЖурковаН. В.ZhurkovaNatal’ya V.

Журкова Наталья Вячеславовна, к.м.н.

Москва

Natal’ya V. Zhurkova, MD, PhD

Moscow

n1972z@yandex.ruНИИ педиатрии и охраны здоровья детей НКЦ №2 ФГБНУ «РНЦХ им. акад. Б.В. Петровского»; РНИМУ им. Н.И. ПироговаРоссияResearch Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery; Pirogov Russian National Research Medical UniversityRussian FederationНИИ педиатрии и охраны здоровья детей НКЦ №2 ФГБНУ «РНЦХ им. акад. Б.В. Петровского»; Первый МГМУ им. И.М. Сеченова (Сеченовский Университет)РоссияResearch Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery; I.M. Sechenov Moscow Medical AcademyRussian FederationНИИ педиатрии и охраны здоровья детей НКЦ №2 ФГБНУ «РНЦХ им. акад. Б.В. Петровского»РоссияResearch Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of SurgeryRussian Federation202317112023205498506Copyright © Сурков А.Н., Баранов А.А., Намазова-Баранова Л.С., Аракелян А.Л., Бессонов Е.Е., Журкова Н.В., 20232023Сурков А.Н., Баранов А.А., Намазова-Баранова Л.С., Аракелян А.Л., Бессонов Е.Е., Журкова Н.В.Surkov A.N., Baranov A.A., Namazova-Baranova L.S., Arakelyan A.L., Bessonov E.E., Zhurkova N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pedpharma.ru/jour/article/view/2361

Болезнь накопления гликогена Ib типа (БНГ Ib) — заболевание из группы наследственных болезней обмена веществ, обусловленное недостаточностью глюкозо-6-фосфатного транспортера (G6PT, SLC37A4), которая приводит к нарушению как гликогенолиза, так и глюконеогенеза и, как следствие, к избыточному накоплению гликогена и жира в печени, почках и слизистой оболочке кишечника. Основные клинические проявления и лабораторные данные включают задержку роста, гепатомегалию, гипогликемию, лактатацидоз, гиперурикемию и гиперлипидемию. Осложнениями данного заболевания являются гепатоцеллюлярная аденома с возможным риском малигнизации, нефропатия и остеопороз. Специфический признак БНГ Ib — нейтропения с нарушением функции нейтрофилов, создающая предпосылки к рецидивирующим инфекциям и развитию воспалительного заболевания кишечника. До настоящего времени ферментозаместительная терапия БНГ Ib не разработана, поэтому основными методами лечения являются специализированная диета с добавлением сырого кукурузного крахмала (для купирования гипогликемии) и применение гранулоцитарного колониестимулирующего фактора (для купирования нейтропении). Однако недавнее установление роли 1,5-ангидроглюцитола в патогенезе дисфункции нейтрофилов при БНГ Ib привело к перепрофилированию показаний к применению эмпаглифлозина — ингибитора почечного натрий-глюкозного котранспортера 2-го типа (SGLT2). В современной литературе сообщается о незначительном, но весьма успешном опыте его применения у пациентов с БНГ Ib (вне рамок официальных показаний к применению) и благоприятном воздействии на дисфункцию нейтрофилов и ее клинические последствия. Как ни странно, этот гипогликемический препарат улучшил не только метаболический, но и гликемический контроль у пациентов с БНГ Ib, несмотря на то, что в основе патологии лежит хроническая гипогликемия. Все больше свидетельств указывают на роль эмпаглифлозина в регуляции клеточного гомеостаза (например, метаболизма жирных кислот, глюкозы, холестерина, апоптоза и клеточной пролиферации, в частности, в печени) путем влияния на активность сиртуина 1 (SIRT1), АМФ-активируемой протеинкиназы (AMPK) и сигнальных молекул, таких как α-серин/треониновая протеинкиназа (Akt) и механическая мишень рапамицина (mTOR), что приводит к улучшению структуры и функции митохондрий, стимуляции аутофагии, снижению окислительного стресса и подавлению воспаления. Модуляция этих путей смещает окислительный метаболизм с углеводов на липиды и приводит к ключевому снижению уровня инсулина, резистентности к нему, глюкозо- и липотоксичности. В настоящем обзоре представлены современные данные о патогенезе нейтропении и возможности применения эмпаглифлозина для ее купирования у пациентов с БНГ Ib.

Glycogen storage disease type Ib (GSD Ib) — is a disease from the group of hereditary metabolic diseases caused by insufficiency of the glucose-6-phosphate transporter (G6PT, SLC37A4), which leads to a violation of both glycogenolysis and gluconeogenesis and, as a consequence, to excessive accumulation of glycogen and fat in the liver, kidneys and intestinal mucosa. The main clinical manifestations and laboratory data include growth retardation, hepatomegaly, hypoglycemia, lactic acidosis, hyperuricemia and hyperlipidemia. Complications of this disease are hepatocellular adenoma with a possible risk of malignancy, nephropathy and osteoporosis. A specific sign of GSD Ib is neutropenia with impaired neutrophil function, which creates prerequisites for recurrent infections and the development of inflammatory bowel disease. Until the present, enzyme replacement therapy of GSD Ib has not been developed, therefore, the main methods of treatment are a specialized diet with the addition of raw corn starch (for relief of hypoglycemia) and the use of granulocyte colony stimulating factor (for relief of neutropenia). However, the recent establishment of the role of 1,5-anhydroglucitol in the pathogenesis of neutrophil dysfunction in GSD Ib has led to a reprofiling of indications for the use of empagliflozin, a type 2 renal sodium—glucose cotransporter inhibitor (SGLT2). In the modern literature, it is reported about a minor, but very successful experience of its use in patients with GSD Ib (outside the framework of official indications for use) and a beneficial effect on neutrophil dysfunction and its clinical consequences. Oddly enough, this hypoglycemic drug improved not only metabolic, but also glycemic control in patients with GSD Ib, despite the fact that the pathology is based on chronic hypoglycemia. More and more evidence points to the role of empagliflozin in the regulation of cellular homeostasis (for example, fatty acid metabolism, glucose, cholesterol, apoptosis and cell proliferation, in particular in the liver) by influencing the activity of sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK) and signal molecules such as -serine/threonine protein kinase (Akt) and a mechanical target of rapamycin (mTOR), which leads to an improvement in the structure and function of mitochondria, stimulation of autophagy, reducing oxidative stress and suppressing inflammation. Modulation of these pathways shifts oxidative metabolism from carbohydrates to lipids and leads to a key decrease in insulin levels, resistance to it, glucose and lipotoxicity. This review presents current data on the pathogenesis of neutropenia and the possibility of using empagliflozin for its relief in patients with GSD Ib.

болезнь накопления гликогена Ib типанейтропениягипогликемияингибитор почечного транспортера глюкозыэмпаглифлозинglycogen storage disease type Ibneutropeniahypoglycemiarenal glucose transporter inhibitorempagliflozinОтсутствуетNot specifiedReferencesChou JY, Jun HS, Mansfield BC. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase/glucose-6-phosphate transporter complexes. J Inherit Metab Dis. 2015;38(3):511–519. doi: https://doi.org/10.1007/s10545-014-9772-xChou JY, Jun HS, Mansfield BC. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase/glucose-6-phosphate transporter complexes. J Inherit Metab Dis. 2015;38(3):511–519. doi: https://doi.org/10.1007/s10545-014-9772-xСурков А.Н. Гликогеновая болезнь у детей: современные представления (часть I) // Вопросы современной педиатрии. — 2012. — Т. 11. — № 2. — С. 30–42. — doi: https://doi.org/10.15690/vsp.v11i2.208Surkov AN. Glycogen storage disease in children: modern concepts (part I). Voprosy sovremennoi pediatrii — Current Pediatrics. 2012;11(2):30–42. (In Russ). doi: https://doi.org/10.15690/vsp.v11i2.208Veiga-da-Cunha M, Gerin I, Chen Y-T, et al. A gene on chromosome 11q23 coding for a putative glucose-6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. Am J Hum Genet. 1998;63(4):976–983. doi: https://doi.org/10.1086/302068Veiga-da-Cunha M, Gerin I, Chen Y-T, et al. A gene on chromosome 11q23 coding for a putative glucose-6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. Am J Hum Genet. 1998;63(4):976–983. doi: https://doi.org/10.1086/302068Баранов А.А., Намазова-Баранова Л.С., Сурков А.Н. и др. Гликогеновая болезнь у детей: учебное пособие. — М.: ПедиатрЪ; 2012. — 128 с.Baranov AA, Namazova-Baranova LS, Surkov AN, et al. Glikogenovaya bolezn’ u detei: Tutorial. Moscow: Pediatr; 2012. 128 p. (In Russ).Kishnani PS, Austin SL, Abdenur JE, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American college of medical genetics and genomics. Genet Med. 2014;16(11):e1–e29. doi: https://doi.org/10.1038/gim.2014.128Kishnani PS, Austin SL, Abdenur JE, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American college of medical genetics and genomics. Genet Med. 2014;16(11):e1–e29. doi: https://doi.org/10.1038/gim.2014.128Visser G, Rake J-P, Fernandes J, et al. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: results of the European study on glycogen storage disease type I. J Pediatr. 2000;137(2):187–191. doi: https://doi.org/10.1067/mpd.2000.105232Visser G, Rake J-P, Fernandes J, et al. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type Ib: results of the European study on glycogen storage disease type I. J Pediatr. 2000;137(2):187–191. doi: https://doi.org/10.1067/mpd.2000.105232Chen MA, Weinstein DA. Glycogen storage diseases: diagnosis, treatment and outcome. Transl Sci Rare Dis. 2016;1:45–72. doi: https://doi.org/10.3233/TRD-160006Chen MA, Weinstein DA. Glycogen storage diseases: diagnosis, treatment and outcome. Transl Sci Rare Dis. 2016;1:45–72. doi: https://doi.org/10.3233/TRD-160006Wortmann SB, Van Hove JLK, Derks TGJ, et al. Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor. Blood. 2020;136(9):1033–1043. doi: https://doi.org/10.1182/blood.2019004465Wortmann SB, Van Hove JLK, Derks TGJ, et al. Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor. Blood. 2020;136(9):1033–1043. doi: https://doi.org/10.1182/blood.2019004465Veiga-da-Cunha M, Chevalier N, Stephenne X, et al. Failure to eliminate a phosphorylated glucose analog leads to neutropenia in patients with G6PT and G6PC3 deficiency. Proc Natl Acad Sci USA. 2019;116(4):1241–1250. doi: https://doi.org/10.1073/pnas.1816143116Veiga-da-Cunha M, Chevalier N, Stephenne X, et al. Failure to eliminate a phosphorylated glucose analog leads to neutropenia in patients with G6PT and G6PC3 deficiency. Proc Natl Acad Sci USA. 2019;116(4):1241–1250. doi: https://doi.org/10.1073/pnas.1816143116Yamanouchi T, Tachibana Y, Akanuma H, et al. Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body. Am J Physiol Metab. 1992;263(2 Pt 1):E268–E273. doi: https://doi.org/10.1152/ajpendo.1992.263.2.E268Yamanouchi T, Tachibana Y, Akanuma H, et al. Origin and disposal of 1,5-anhydroglucitol, a major polyol in the human body. Am J Physiol Metab. 1992;263(2 Pt 1):E268–E273. doi: https://doi.org/10.1152/ajpendo.1992.263.2.E268Crane RK, Sols A. The non-competitive inhibition of brain hexokinase by glucose-6-Phosphate and related compounds. J Biol Chem. 1954;210(2):597–606. doi: https://doi.org/10.1016/S0021-9258(18)65385-2Crane RK, Sols A. The non-competitive inhibition of brain hexokinase by glucose-6-Phosphate and related compounds. J Biol Chem. 1954;210(2):597–606. doi: https://doi.org/10.1016/S0021-9258(18)65385-2Maiorana A, Tagliaferri F, Dionisi-Vici C. Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders. Front Endocrinol (Lausanne). 2023;14:1145111. doi: https://doi.org/10.3389/fendo.2023.1145111Maiorana A, Tagliaferri F, Dionisi-Vici C. Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders. Front Endocrinol (Lausanne). 2023;14:1145111. doi: https://doi.org/10.3389/fendo.2023.1145111Melis D, Parenti G, Della Casa R, et al. Crohn’s-like ileo-colitis in patients affected by glycogen storage disease Ib: two years’ follow-up of patients with a wide spectrum of gastrointestinal signs. Acta Paediatr. 2003;92(12):1415–1421. doi: https://doi.org/10.1080/08035250310007033Melis D, Parenti G, Della Casa R, et al. Crohn’s-like ileo-colitis in patients affected by glycogen storage disease Ib: two years’ follow-up of patients with a wide spectrum of gastrointestinal signs. Acta Paediatr. 2003;92(12):1415–1421. doi: https://doi.org/10.1080/08035250310007033Wicker C, Roda C, Perry A, et al. Infectious and digestive complications in glycogen storage disease type Ib: study of a French cohort. Mol Genet Metab Rep. 2020;23:100581. doi: https://doi.org/10.1016/j.ymgmr.2020.100581Wicker C, Roda C, Perry A, et al. Infectious and digestive complications in glycogen storage disease type Ib: study of a French cohort. Mol Genet Metab Rep. 2020;23:100581. doi: https://doi.org/10.1016/j.ymgmr.2020.100581Rake JP, Visser G, Labrune P, et al. European Study on glycogen storage disease type I (ESGSD I). Guidelines for management of glycogen storage disease type I — European study on glycogen storage disease type I (ESGSD I). Eur J Pediatr. 2002;161 Suppl:S112–S119. doi: https://doi.org/10.1007/s00431-002-1016-7Rake JP, Visser G, Labrune P, et al. European Study on glycogen storage disease type I (ESGSD I). Guidelines for management of glycogen storage disease type I — European study on glycogen storage disease type I (ESGSD I). Eur J Pediatr. 2002;161 Suppl:S112– S119. doi: https://doi.org/10.1007/s00431-002-1016-7Visser G, Rake J, Labrune P, et al. Consensus guidelines for management of glycogen storage disease type 1b — European study on glycogen storage disease type 1. Eur J Pediatr. 2002;161 Suppl:S120–S123. doi: https://doi.org/10.1007/s00431-002-1017-6Visser G, Rake J, Labrune P, et al. Consensus guidelines for management of glycogen storage disease type 1b — European study on glycogen storage disease type 1. Eur J Pediatr. 2002;161 Suppl:S120–S123. doi: https://doi.org/10.1007/s00431-002-1017-6Сурков А.Н., Черников В.В., Баранов А.А. и др. Результаты оценки качества жизни детей с печеночной формой гликогеновой болезни // Педиатрическая фармакология. — 2013. — Т. 10. — № 4. — С. 90–94. — doi: https://doi.org/10.15690/pf.v10i4.759Surkov AN, Chernikov VV, Baranov AA, et al. Results of Life Quality Evaluation in Children with Hepatic Variant of Glycogen Disease. Pediatricheskaya Farmakologiya — Pediatric pharmacology. 2013;10(4):90–94. (In Russ). doi: https://doi.org/10.15690/pf.v10i4.759Visser G, Rake J, Labrune P, et al. Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European study on glycogen storage disease type 1. Eur J Pediatr. 2002;161 Suppl:S83–S87. doi: https://doi.org/10.1007/s00431-002-1010-0Visser G, Rake J, Labrune P, et al. Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European study on glycogen storage disease type 1. Eur J Pediatr. 2002;161 Suppl:S83–S87. doi: https://doi.org/10.1007/s00431-002-1010-0Li AM, Thyagu S, Maze D, et al. Prolonged granulocyte colony stimulating factor use in glycogen storage disease type 1b associated with acute myeloid leukemia and with shortened telomere length. Pediatr Hematol Oncol. 2018;35(1):45–51. doi: https://doi.org/10.1080/08880018.2018.1440675Li AM, Thyagu S, Maze D, et al. Prolonged granulocyte colony stimulating factor use in glycogen storage disease type 1b associated with acute myeloid leukemia and with shortened telomere length. Pediatr Hematol Oncol. 2018;35(1):45–51. doi: https://doi.org/10.1080/08880018.2018.1440675Dale DC, Bolyard AA, Marrero T, et al. Neutropenia in glycogen storage disease Ib. Curr Opin Hematol. 2019;26:16–21. doi: https://doi.org/10.1097/MOH.0000000000000474Dale DC, Bolyard AA, Marrero T, et al. Neutropenia in glycogen storage disease Ib. Curr Opin Hematol. 2019;26:16–21. doi: https://doi.org/10.1097/MOH.0000000000000474Boulanger C, Stephenne X, Diederich J, et al. Successful use of empagliflozin to treat neutropenia in two G6PC3-deficient children: impact of a mutation in SGLT5. J Inherit Metab Dis. 2022;45(4):759–768. doi: https://doi.org/10.1002/jimd.12509Boulanger C, Stephenne X, Diederich J, et al. Successful use of empagliflozin to treat neutropenia in two G6PC3-deficient children: impact of a mutation in SGLT5. J Inherit Metab Dis. 2022;45(4):759– 768. doi: https://doi.org/10.1002/jimd.12509Makrilakis K, Barmpagianni A, Veiga-da-Cunha M. Repurposing of empagliflozin as a possible treatment for neutropenia and inflammatory bowel disease in glycogen storage disease type Ib: a case report. Cureus. 2022;14(7):12–15. doi: https://doi.org/10.7759/cureus.27264Makrilakis K, Barmpagianni A, Veiga-da-Cunha M. Repurposing of empagliflozin as a possible treatment for neutropenia and inflammatory bowel disease in glycogen storage disease type Ib: a case report. Cureus. 2022;14(7):12–15. doi: https://doi.org/10.7759/cureus.27264Akanuma Y, Morita M, Fukuzawa N, et al. Urinary excretion of 1,5-anhydro-D-glucitol accompanying glucose excretion in diabetic patients. Diabetologia. 1988;31(11):831–835. doi: https://doi.org/10.1007/BF00277486Akanuma Y, Morita M, Fukuzawa N, et al. Urinary excretion of 1,5-anhydro-D-glucitol accompanying glucose excretion in diabetic patients. Diabetologia. 1988;31(11):831–835. doi: https://doi.org/10.1007/BF00277486Chao EC, Henry RR. SGLT2 inhibition — a novel strategy for diabetes treatment. Nat Rev Drug Discov. 2010;9(7):551–559. doi: https://doi.org/10.1038/nrd3180Chao EC, Henry RR. SGLT2 inhibition — a novel strategy for diabetes treatment. Nat Rev Drug Discov. 2010;9(7):551–559. doi: https://doi.org/10.1038/nrd3180Fortuna D, McCloskey LJ, Stickle DF. Model analysis of effect of canagliflozin (Invokana), a sodium–glucose cotransporter 2 inhibitor, to alter plasma 1,5-anhydroglucitol. Clin Chim Acta. 2016;452:138–141. doi: https://doi.org/10.1016/j.cca.2015.11.010Fortuna D, McCloskey LJ, Stickle DF. Model analysis of effect of canagliflozin (Invokana), a sodium–glucose cotransporter 2 inhibitor, to alter plasma 1,5-anhydroglucitol. Clin Chim Acta. 2016;452:138– 141. doi: https://doi.org/10.1016/j.cca.2015.11.010DeFronzo RA, Hompesch M, Kasichayanula S, et al. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care. 2013;36(10):3169–3176. doi: https://doi.org/10.2337/dc13-0387DeFronzo RA, Hompesch M, Kasichayanula S, et al. Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care. 2013;36(10):3169–3176. doi: https://doi.org/10.2337/dc13-0387Grünert SC, Elling R, Maag B, et al. Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib. Orphanet J Rare Dis. 2020;15(1):218. doi: https://doi.org/10.1186/s13023-020-01503-8Grünert SC, Elling R, Maag B, et al. Improved inflammatory bowel disease, wound healing and normal oxidative burst under treatment with empagliflozin in glycogen storage disease type Ib. Orphanet J Rare Dis. 2020;15(1):218. doi: https://doi.org/10.1186/s13023-020-01503-8Rossi A, Miele E, Fecarotta S, et al. Crohn disease-like enterocolitis remission after empagliflozin treatment in a child with glycogen storage disease type Ib: a case report. Ital J Pediatr. 2021;47(1):149. doi: https://doi.org/10.1186/s13052-021-01100-wRossi A, Miele E, Fecarotta S, et al. Crohn disease-like enterocolitis remission after empagliflozin treatment in a child with glycogen storage disease type Ib: a case report. Ital J Pediatr. 2021;47(1):149. doi: https://doi.org/10.1186/s13052-021-01100-wCeccarani C, Bassanini G, Montanari C, et al. Proteobacteria overgrowth and butyrate-producing taxa depletion in the gut microbiota of glycogen storage disease type 1 patients. Metabolites. 2020;10(4):133. doi: https://doi.org/10.3390/metabo10040133Ceccarani C, Bassanini G, Montanari C, et al. Proteobacteria overgrowth and butyrate-producing taxa depletion in the gut microbiota of glycogen storage disease type 1 patients. Metabolites. 2020;10(4):133. doi: https://doi.org/10.3390/metabo10040133Mikami M, Arai A, Mizumoto H. Empagliflozin ameliorated neutropenia in a girl with glycogen storage disease Ib. Pediatr Int. 2021;63(11):1394–1396. doi: https://doi.org/10.1111/ped.14629Mikami M, Arai A, Mizumoto H. Empagliflozin ameliorated neutropenia in a girl with glycogen storage disease Ib. Pediatr Int. 2021;63(11):1394–1396. doi: https://doi.org/10.1111/ped.14629Kaczor M, Greczan M, Kierus K, et al. Sodium-glucose cotransporter type 2 channel inhibitor: breakthrough in the treatment of neutropenia in patients with glycogen storage disease type 1b? JIMD Rep. 2022;63(3):199–206. doi: https://doi.org/10.1002/jmd2.12278Kaczor M, Greczan M, Kierus K, et al. Sodium-glucose cotransporter type 2 channel inhibitor: breakthrough in the treatment of neutropenia in patients with glycogen storage disease type 1b? JIMD Rep. 2022;63(3):199–206. doi: https://doi.org/10.1002/ jmd2.12278Grünert SC, Rosenbaum-Fabian S, Schumann A, et al. Two successful pregnancies and first use of empagliflozin during pregnancy in glycogen storage disease type Ib. JIMD Rep. 2022;63(4):303–308. doi: https://doi.org/10.1002/jmd2.12295Grünert SC, Rosenbaum-Fabian S, Schumann A, et al. Two successful pregnancies and first use of empagliflozin during pregnancy in glycogen storage disease type Ib. JIMD Rep. 2022;63(4):303–308. doi: https://doi.org/10.1002/jmd2.12295Halligan RK, Dalton RN, Turner C, et al. Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre. Orphanet J Rare Dis. 2022;17(1):195. doi: https://doi.org/10.1186/s13023-022-02345-2Halligan RK, Dalton RN, Turner C, et al. Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre. Orphanet J Rare Dis. 2022;17(1):195. doi: https:// doi.org/10.1186/s13023-022-02345-2Bidiuk J, Gaciong Z, Sobieraj P. The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience. Arch Med Sci. 2022;18(4):1095–1099. doi: https://doi.org/10.5114/aoms/150029Bidiuk J, Gaciong Z, Sobieraj P. The overall benefits of empagliflozin treatment in adult siblings with glycogen storage disease type Ib: one year experience. Arch Med Sci. 2022;18(4):1095–1099. doi: https://doi.org/10.5114/aoms/150029Hexner-Erlichman Z, Veiga-da-Cunha M, Zehavi Y, et al. Favorable outcome of empagliflozin treatment in two pediatric glycogen storage disease type 1b patients. Front Pediatr. 2022;10:1071464. doi: https://doi.org/10.3389/fped.2022.1071464Hexner-Erlichman Z, Veiga-da-Cunha M, Zehavi Y, et al. Favorable outcome of empagliflozin treatment in two pediatric glycogen storage disease type 1b patients. Front Pediatr. 2022;10:1071464. doi: https://doi.org/10.3389/fped.2022.1071464Tallis E, Karsenty CL, Grimes AB, et al. Untargeted metabolomic profiling in a patient with glycogen storage disease Ib receiving empagliflozin treatment. JIMD Rep. 2022;63(4):309–315. doi: https://doi.org/10.1002/jmd2.12304Tallis E, Karsenty CL, Grimes AB, et al. Untargeted metabolomic profiling in a patient with glycogen storage disease Ib receiving empagliflozin treatment. JIMD Rep. 2022;63(4):309–315. doi: https://doi.org/10.1002/jmd2.12304Mathis T, Poms M, Köfeler H, et al. Untargeted plasma metabolomics identifies broad metabolic perturbations in glycogen storage disease type I. J Inherit Metab Dis. 2022;45(2):235–247. doi: https://doi.org/10.1002/jimd.12451Mathis T, Poms M, Köfeler H, et al. Untargeted plasma metabolomics identifies broad metabolic perturbations in glycogen storage disease type I. J Inherit Metab Dis. 2022;45(2):235–247. doi: https://doi.org/10.1002/jimd.12451Grünert SC, Derks TGJ, Adrian K, et al. Efficacy and safety of empagliflozin in glycogen storage disease type Ib: data from an international questionnaire. Genet Med. 2022;24(8):1781–1788. doi: https://doi.org/10.1016/j.gim.2022.04.001Grünert SC, Derks TGJ, Adrian K, et al. Efficacy and safety of empagliflozin in glycogen storage disease type Ib: data from an international questionnaire. Genet Med. 2022;24(8):1781–1788. doi: https://doi.org/10.1016/j.gim.2022.04.001Rajas F, Labrune P, Mithieux G. Glycogen storage disease type 1 and diabetes: learning by comparing and contrasting the two disorders. Diabetes Metab. 2013;39(5):377–877. doi: https://doi.org/10.1016/j.diabet.2013.03.002Rajas F, Labrune P, Mithieux G. Glycogen storage disease type 1 and diabetes: learning by comparing and contrasting the two disorders. Diabetes Metab. 2013;39(5):377–877. doi: https://doi.org/10.1016/j.diabet.2013.03.002Курбатова О.В., Измайлова Т.Д., Сурков А.Н. и др. Митохондриальная дисфункция у детей с печеночными формами гликогеновой болезни // Вестник Российской академии медицинских наук. — 2014. — Т. 69. — № 7-8. — С. 78–84. — doi: https://doi.org/10.15690/vramn.v69i7-8.1112Kurbatova OV, Izmajlova TD, Surkov AN, et al. Mitochondrial Dysfunction in Children with Hepatic Forms of Glycogen Storage Disease. Vestnik Rossiiskoi Akademii Meditsinskikh Nauk — Annals of the Russian Academy of Medical Sciences. 2014;69(7-8):78–84. (In Russ). doi: https://doi.org/10.15690/vramn.v69i7-8.1112Melis D, Rossi A, Pivonello R, et al. Glycogen storage disease type ia (GSD Ia) but not glycogen storage disease type Ib (GSD Ib) is associated to an increased risk of metabolic syndrome: possible role of microsomal glucose 6-phosphate accumulation. Orphanet J Rare Dis. 2015;10:91. doi: https://doi.org/10.1186/s13023-015-0301-2Melis D, Rossi A, Pivonello R, et al. Glycogen storage disease type ia (GSD Ia) but not glycogen storage disease type Ib (GSD Ib) is associated to an increased risk of metabolic syndrome: possible role of microsomal glucose 6-phosphate accumulation. Orphanet J Rare Dis. 2015;10:91. doi: https://doi.org/10.1186/s13023-015-0301-2Rossi A, Simeoli C, Salerno M, et al. Imbalanced cortisol concentrations in glycogen storage disease type I: evidence for a possible link between endocrine regulation and metabolic derangement. Orphanet J Rare Dis. 2020;15(1):99. doi: https://doi.org/10.1186/s13023-020-01377-wRossi A, Simeoli C, Salerno M, et al. Imbalanced cortisol concentrations in glycogen storage disease type I: evidence for a possible link between endocrine regulation and metabolic derangement. Orphanet J Rare Dis. 2020;15(1):99. doi: https://doi.org/10.1186/s13023-020-01377-wRossi A, Ruoppolo M, Formisano P, et al. Insulin-resistance in glycogen storage disease type Ia: linking carbohydrates and mitochondria? J Inherit Metab Dis. 2018;41(6):985–995. doi: https://doi.org/10.1007/s10545-018-0149-4Rossi A, Ruoppolo M, Formisano P, et al. Insulin-resistance in glycogen storage disease type Ia: linking carbohydrates and mitochondria? J Inherit Metab Dis. 2018;41(6):985–995. doi: https://doi.org/10.1007/s10545-018-0149-4Bhattacharya K. Dietary dilemmas in the management of glycogen storage disease type I. J Inherit Metab Dis. 2011;34(3):621–629. doi: https://doi.org/10.1007/s10545-011-9322-8Bhattacharya K. Dietary dilemmas in the management of glycogen storage disease type I. J Inherit Metab Dis. 2011;34(3):621–629. doi: https://doi.org/10.1007/s10545-011-9322-8Dahlberg KR, Ferrecchia IA, Dambska-Williams M, et al. Cornstarch requirements of the adult glycogen storage disease Ia population: a retrospective review. J Inherit Metab Dis. 2020;43(2):269–278. doi: https://doi.org/10.1002/jimd.12160Dahlberg KR, Ferrecchia IA, Dambska-Williams M, et al. Cornstarch requirements of the adult glycogen storage disease Ia population: a retrospective review. J Inherit Metab Dis. 2020;43(2):269–278. doi: https://doi.org/10.1002/jimd.12160Rossi A, Hoogeveen IJ, Bastek VB, et al. Dietary lipids in glycogen storage disease type III: a systematic literature study, case studies, and future recommendations. J Inherit Metab Dis. 2020;43(4):770–777. doi: https://doi.org/10.1002/jimd.12224Rossi A, Hoogeveen IJ, Bastek VB, et al. Dietary lipids in glycogen storage disease type III: a systematic literature study, case studies, and future recommendations. J Inherit Metab Dis. 2020;43(4):770– 777. doi: https://doi.org/10.1002/jimd.12224Qian H, Chao X, Williams J, et al. Autophagy in liver diseases: a review. Mol Aspects Med. 2021;82:100973. doi: https://doi.org/10.1016/j.mam.2021.100973Qian H, Chao X, Williams J, et al. Autophagy in liver diseases: a review. Mol Aspects Med. 2021;82:100973. doi: https://doi.org/10.1016/j.mam.2021.100973Halaby CA, Young SP, Austin S, et al. Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring. Genet Med. 2019;21(12):2686–2694. doi: https://doi.org/10.1038/s41436-019-0561-7Halaby CA, Young SP, Austin S, et al. Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring. Genet Med. 2019;21(12):2686–2694. doi: https://doi.org/10.1038/s41436-019-0561-7Gautam S, Zhang L, Lee C, et al. Molecular mechanism underlying impaired hepatic autophagy in glycogen storage disease type Ib. Hum Mol Genet. 2023;32(2):262–275. doi: https://doi.org/10.1093/hmg/ddac197Gautam S, Zhang L, Lee C, et al. Molecular mechanism underlying impaired hepatic autophagy in glycogen storage disease type Ib. Hum Mol Genet. 2023;32(2):262–275. doi: https://doi.org/10.1093/hmg/ddac197Busch V, Gempel K, Hack A, et al. Treatment of glycogenosis type V with ketogenic diet. Ann Neurol. 2005;58(2):341. doi: https://doi.org/10.1002/ana.20565Busch V, Gempel K, Hack A, et al. Treatment of glycogenosis type V with ketogenic diet. Ann Neurol. 2005;58(2):341. doi: https://doi.org/10.1002/ana.20565Vorgerd M, Zange J. Treatment of glycogenosys type V (McArdle disease) with creatine and ketogenic diet with clinical scores and with 31P-MRS on working leg muscle. Acta Myol. 2007;26(1):61–63.Vorgerd M, Zange J. Treatment of glycogenosys type V (McArdle disease) with creatine and ketogenic diet with clinical scores and with 31P-MRS on working leg muscle. Acta Myol. 2007;26(1):61– 63.Løkken N, Hansen KK, Storgaard JH, et al. Titrating a modified ketogenic diet for patients with McArdle disease: a pilot study. J Inherit Metab Dis. 2020;43(4):778–786. doi: https://doi.org/10.1002/jimd.12223Løkken N, Hansen KK, Storgaard JH, et al. Titrating a modified ketogenic diet for patients with McArdle disease: a pilot study. J Inherit Metab Dis. 2020;43(4):778–786. doi: https://doi.org/10.1002/jimd.12223Similä ME, Auranen M, Piirilä PL. Beneficial effects of ketogenic diet on phosphofructokinase deficiency (Glycogen storage disease type VII). Front Neurol. 2020;11:57. doi: https://doi.org/10.3389/fneur.2020.00057Similä ME, Auranen M, Piirilä PL. Beneficial effects of ketogenic diet on phosphofructokinase deficiency (Glycogen storage disease type VII). Front Neurol. 2020;11:57. doi: https://doi.org/10.3389/fneur.2020.00057Donnan JR, Grandy CA, Chibrikov E, et al. Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ Open. 2019;9(1):e02257. doi: https://doi.org/10.1136/bmjopen-2018-022577Donnan JR, Grandy CA, Chibrikov E, et al. Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ Open. 2019;9(1):e02257. doi: https://doi.org/10.1136/bmjopen-2018-022577Rosenstock J, Jelaska A, Frappin G, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014;37(7):1815–1823. doi: https://doi.org/10.2337/dc13-3055Rosenstock J, Jelaska A, Frappin G, et al. Improved glucose control with weight loss, lower insulin doses, and no increased hypoglycemia with empagliflozin added to titrated multiple daily injections of insulin in obese inadequately controlled type 2 diabetes. Diabetes Care. 2014;37(7):1815–1823. doi: https://doi.org/10.2337/dc13-3055dos Santos SS, Ramaldes LA, Gabbay MAL, et al. Use of a sodium-glucose cotransporter 2 inhibitor, empagliflozin, in a patient with rabson-mendenhall syndrome. Horm Res Paediatr. 2021;94(7-8):313–316. doi: https://doi.org/10.1159/000519613dos Santos SS, Ramaldes LA, Gabbay MAL, et al. Use of a sodium-glucose cotransporter 2 inhibitor, empagliflozin, in a patient with rabson-mendenhall syndrome. Horm Res Paediatr. 2021;94(7- 8):313–316. doi: https://doi.org/10.1159/000519613Galderisi A, Tamborlane W, Taylor SI, et al. SGLT2i improves glycemic control in patients with congenital severe insulin resistance. Pediatrics. 2022;150(1):e2021055671. doi: https://doi.org/10.1542/peds.2021-055671Galderisi A, Tamborlane W, Taylor SI, et al. SGLT2i improves glycemic control in patients with congenital severe insulin resistance. Pediatrics. 2022;150(1):e2021055671. doi: https://doi.org/10.1542/peds.2021-055671Chen Y-T, Kishnani PS, Koeberl D. Glycogen storage diseases. In: The online metabolic and molecular bases of inherited disease. Valle DL, Antonarakis S, Ballabio A, et al., eds. New York, NY: McGraw-Hill Education; 2019. Available online: https://ommbid.mhmedical.com/content.aspx?aid=1181420647. Accessed on October 17, 2023.Chen Y-T, Kishnani PS, Koeberl D. Glycogen storage diseases. In: The online metabolic and molecular bases of inherited disease. Valle DL, Antonarakis S, Ballabio A, et al., eds. New York, NY: McGraw-Hill Education; 2019. Available online: https://ommbid.mhmedical.com/content.aspx?aid=1181420647. Accessed on October 17, 2023.Ng ES-T, Gupta S, Khin SM, Mak A. Gout, anemia, and hepatomegaly in a young man with glycogen storage disease. JCR J Clin Rheumatol. 2012;18(4):222–223. doi: https://doi.org/10.1097/RHU.0b013e3182598ed1Ng ES-T, Gupta S, Khin SM, Mak A. Gout, anemia, and hepatomegaly in a young man with glycogen storage disease. JCR J Clin Rheumatol. 2012;18(4):222–223. doi: https://doi.org/10.1097/RHU.0b013e3182598ed1Ouchi M, Oba K, Aoyama J, et al. Serum uric acid in relation to serum 1,5-anhydroglucitol levels in patients with and without type 2 diabetes mellitus. Clin Biochem. 2013;46(15):1436–1441. doi: https://doi.org/10.1016/j.clinbiochem.2013.06.003Ouchi M, Oba K, Aoyama J, et al. Serum uric acid in relation to serum 1,5-anhydroglucitol levels in patients with and without type 2 diabetes mellitus. Clin Biochem. 2013;46(15):1436–1441. doi: https://doi.org/10.1016/j.clinbiochem.2013.06.003

The authors declare that there are no conflicts of interest present.