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Background: Cohort data on continuous glucose monitoring (CGM) metrics are scarce for liver glycogen storage diseases (GSDs) and idiopathic ketotic hypoglycemia (IKH). The aim of this study was to retrospectively describe CGM metrics for people with liver GSDs and IKH., Patients and Methods: CGM metrics (descriptive, glycemic variation and glycemic control parameters) were calculated for 47 liver GSD and 14 IKH patients, categorized in cohorts by disease subtype, age and treatment status, and compared to published age-matched CGM metrics from healthy individuals. Glycemic control was assessed as time-in-range (TIR; ≥3.9 - ≤7.8 and ≥3.9 - ≤10.0 mmol/L), time-below-range (TBR; <3.0 mmol/L and ≥3.0 - ≤3.9 mmol/L), and time-above-range (TAR; >7.8 and >10.0 mmol/L)., Results: Despite all patients receiving dietary treatment, GSD cohorts displayed significantly different CGM metrics compared to healthy individuals. Decreased TIR together with increased TAR were noted in GSD I, GSD III, and GSD XI (Fanconi-Bickel syndrome) cohorts (all p < 0.05). In addition, all GSD I cohorts showed increased TBR (all p < 0.05). In GSD IV an increased TBR (p < 0.05) and decreased TAR were noted (p < 0.05). In GSD IX only increased TAR was observed (p < 0.05). IKH patient cohorts, both with and without treatment, presented CGM metrics similar to healthy individuals., Conclusion: Despite dietary treatment, most liver GSD cohorts do not achieve CGM metrics comparable to healthy individuals. International recommendations on the use of CGM and clinical targets for CGM metrics in liver GSD patients are warranted, both for patient care and clinical trials., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest related to the content of this manuscript. R.J.O.: There are confidentiality agreements with third parties. There is a consultation agreement (with Ultragenyx Pharmaceutical Inc). For all private-public relationships, all contracts are via UMCG Contract Research Desk and all payments are to UMCG. A.V., C.M.A.L.: No conflicts of interest. M.J.F.W., F.D.B., A.B.S.: There are confidentiality agreements with third parties. For all private-public relationships, all contracts are via UMCG Contract Research Desk and all payments are to UMCG. A.R.: There are confidentiality agreements with third parties. In the past 36 months there have been consultation agreements or honoraria for lectures or presentations with Nestlé, Danone and Ultragenyx Pharmaceutical Inc. T.G.J.D.: There are confidentiality agreements with third parties. In the past 36 months, there have been consultation agreements (with Danone, Ultragenyx Pharmaceutical Inc, ModernaTX Inc., and Beam Therapeutics), contracts for financial research support for investigator-initiated research (NCT04311307) and sponsor-initiated research (NCT03517085, NCT03970278, NCT05139316, and NCT05196165), honoraria for lectures or presentations (by MEDTalks, Prelum, and Danone), and participations in a Data Safety Monitoring Board (NCT05095727) and Advisory Boards (Ultragenyx Pharmaceutical Inc, ModernaTX Inc., and Beam Therapeutics). For all private-public relationships, all contracts are via UMCG Contract Research Desk and all payments are to UMCG., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Off-label repurposing of empagliflozin allows pathomechanism-based treatment of neutropenia/neutrophil-dysfunction in glycogen storage disease type Ib (GSDIb). From a value-based healthcare (VBHC) perspective, we here retrospectively studied patient-reported, clinical and pharmacoeconomic outcomes in 11 GSDIb individuals before and under empagliflozin at two centers (the Netherlands [NL], Austria [AT]), including a budget impact analysis, sensitivity-analysis, and systematic benefit-risk assessment. Under empagliflozin, all GSDIb individuals reported improved quality-of-life-scores. Neutrophil dysfunction related symptoms allowed either granulocyte colony-stimulating factor cessation or tapering. Calculated cost savings per patient per year ranged between € 6482-14 190 (NL) and € 1281-41 231 (AT). The budget impact analysis estimated annual total cost savings ranging between € 75 062-225 716 (NL) and € 37 697-231 790 (AT), based on conservative assumptions. The systematic benefit-risk assessment was favorable. From a VBHC perspective, empagliflozin treatment in GSDIb improved personal and clinical outcomes while saving costs, thereby creating value at multiple pillars. We emphasize the importance to reimburse empagliflozin for GSDIb individuals, further supported by the favorable systematic benefit-risk assessment. These observations in similar directions in two countries/health care systems strongly suggest that our findings can be extrapolated to other geographical areas and health care systems., (© 2024 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

In patients with glycogen storage disease type Ib (GSD Ib), quality of life is severely hampered by neutropenia and neutropenia-associated symptoms. SGLT2 inhibitors are a new treatment option and have shown improved medical outcomes in more than 120 patients so far. The aim of this international questionnaire study was to assess patient-reported outcomes of this new treatment in GSD Ib patients. Patients and caregivers of pediatric patients were invited to complete a web-based questionnaire. This was designed to evaluate treatment effects of the SGLT2 inhibitor empagliflozin on clinical symptoms and important aspects of daily life including physical performance, sleep, social and work life, traveling, socioeconomic aspects, and quality of life. The questionnaire was completed by 73 respondents from 17 different countries. The mean duration of treatment was 15 months, the cumulative treatment time was 94.8 years. More than 80% of patients reported an improved quality of life. The number of hospitalizations was reduced (66% of patients), as well as the number of days absent from school or work. Granulocyte colony-stimulating factor (G-CSF) treatment could be stopped in 49% of patients and reduced in another 42%. Clear improvement of neutropenia and all neutropenia-associated symptoms was reported by the majority of patients. Additionally, patients or caregivers reported positive effects on appetite (63%), level of activity (75%), overall well-being (96%), and sleep (63%). Empagliflozin positively impacts many aspects of daily life including work and social life and thereby significantly improves quality of life of patients and caregivers., Competing Interests: The authors declare that they have no competing interests concerning the content of this manuscript., (© 2023 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Value-based healthcare (VBHC) intends to achieve better outcomes for patients, to improve quality of patient care, with reduced costs. Four dimensions define a model of intimately related value-pillars: personal value, allocative value, technical value, and societal value. VBHC is mostly applied in common diseases, and there are fundamental challenges in applying VBHC strategies to low volume, high complex healthcare situations, such as rare diseases, including inherited metabolic disorders. This article summarizes current practices at various academical domains (i.e., research, healthcare, education, and training) that (aim to) increase values at various value-pillars for persons with liver glycogen storage diseases or fatty acid oxidation disorders and their families. Future perspectives may include facilitating virtual networks to function as integrated practice units, improving measurement of outcomes, and creating information technology platforms to overcome the ethical, legal, societal, and technical challenges of data sharing for healthcare and research purposes., (© 2022 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Context: Although previous research has shown the benefit of continuous glucose monitoring (CGM) for hepatic glycogen storage diseases (GSDs), current lack of prospectively collected CGM metrics and glycemic targets for CGM-derived outcomes in the hepatic GSD population limits its use., Objective: To assess CGM metrics for glycemic variation and glycemic control in adult patients with GSDIa as compared to matched healthy volunteers., Design: Prospective CGM data were collected during the ENGLUPRO GSDIa trial (NCT04311307) in which a Dexcom G6 device was used. Ten adult patients with GSDIa and 10 age-, sex- and body mass index-matched healthy volunteers were enrolled. Capillary blood glucose was concurrently measured during 2 standardized 2-hour time intervals. Descriptive [eg, glycemic variability (GV), time below range, time in range (TIR), time above range (TAR)] and advanced (ie, first- and second-order derivatives, Fourier analysis) CGM outcomes were calculated. For each descriptive CGM outcome measure, 95% CIs were computed in patients with GSDIa and healthy volunteers, respectively., Results: CGM overestimation was higher under preprandial and level 1 hypoglycemia (ie, capillary glucose values ≥ 3.0 mmol/L and < 3.9 mmol/L) conditions. GV and TAR were higher while TIR was lower in patients with GSDIa compared to healthy volunteers (P < 0.05). Three patients with GSDIa showed descriptive CGM outcomes outside the calculated 95% CI in GSDIa patients. Advanced CGM analysis revealed a distinct pattern (ie, first- and second-order derivatives and glucose curve amplitude) in each of these 3 patients within the patients group., Conclusions: This is the first study to prospectively compare CGM outcomes between adult patients with GSDIa and matched healthy volunteers. The generation of a set of CGM metrics will provide guidance in using and interpreting CGM data in GSDIa and will be useful for the definition of glycemic targets for CGM in patients with GSDIa. Future studies should investigate the prognostic value of CGM outcomes and their major determinants in patients with GSDIa., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

There is a paucity in literature on eating and psychosocial problems in patients with hepatic glycogen storage disease (GSD) and idiopathic ketotic hypoglycemia (IKH), problems that can greatly affect quality of life. This is a monocentre, retrospective, observational mixed method study of patients with hepatic GSD or IKH treated at the Beatrix Children's Hospital Groningen, who had been referred to SeysCentra, a specialist centre for the treatment of eating problems. Additionally, a systematic literature review has been performed to identify instruments to quantify patient-reported outcome measures of psychosocial problems in hepatic GSD patients. Sixteen patients from 12 families were included with ages ranging between 3 and 24 years. Five out of sixteen patients were diagnosed with Avoidant/Restrictive Food Intake Disorder and six patients showed characteristics of this disorder. Fourteen patients experienced sleeping problems, and 11 out of 12 parent couples experienced stress about the illness of their child. We subsequently identified 26 instruments to quantify patient-reported outcome measures for GSD patients. This study demonstrates that GSD patients can develop Avoidant/Restrictive Food Intake Disorder influencing quality of life at multiple domains. The identification of instruments to assess psychosocial wellbeing is an important step towards a standard set of patient-reported outcome measures., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)