{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T09:18:12Z","timestamp":1778059092085,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Glycogen storage disease type IX (GSD IX) is an inherited metabolic disorder characterized by marked clinical heterogeneity and variable severity. Dietary therapy is considered the cornerstone of management, but evidence on treatment strategies, efficacy, and safety remains limited. This study aimed to systematically synthesize available data on therapeutic approaches and clinical outcomes in GSD IX. Methods: A focused analysis of treatment-related data was conducted from a previously performed PRISMA-based systematic review. Clinical studies reporting treatment and follow-up data in genetically confirmed GSD IX patients were included. Results: Among 400 patients identified in the original review, 129 from 26 studies had treatment and follow-up data available. Dietary management combined with uncooked cornstarch (UCCS) was the most common approach (96.1%), with highly heterogeneous protocols. Hepatic manifestations improved in 59\/129 (45.7%) of patients, and hypoglycemia in 45\/129 (34.9%). Growth outcomes were variable, with catch-up growth in 14.0% and persistent impairment in 19.4%, although data were often missing. Muscle involvement was rarely assessed. No treatment-related adverse events were reported. However, disease-related complications were described, including liver cirrhosis, neurological involvement, osteopenia\/osteoporosis, and two deaths in GSD IXa patients. Conclusions: Dietary therapy combined with UCCS remains the mainstay of treatment in GSD IX and is associated with improvement in key clinical domains. However, evidence is limited, heterogeneous, and largely based on small studies. Data on modified cornstarch formulations, such as Glycosade\u00ae, are scarce. Prospective studies and standardized treatment protocols are needed to support evidence-based management.<\/jats:p>","DOI":"10.3390\/children13050648","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T07:36:23Z","timestamp":1778052983000},"page":"648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dietary and Therapeutic Management of Glycogen Storage Disease Type IX: Analysis of a Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4805-310X","authenticated-orcid":false,"given":"Giulia","family":"Montanari","sequence":"first","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Zanaroli","sequence":"additional","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Specialty School of Pediatrics, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4573-9314","authenticated-orcid":false,"given":"Egidio","family":"Candela","sequence":"additional","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, via Massarenti, 11, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7441-9248","authenticated-orcid":false,"given":"Giacomo","family":"Biasucci","sequence":"additional","affiliation":[{"name":"Pediatrics and Neonatology Unit, Guglielmo da Saliceto Hospital, 29121 Piacenza, Italy"},{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3470-6880","authenticated-orcid":false,"given":"Federico","family":"Baronio","sequence":"additional","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8218-1463","authenticated-orcid":false,"given":"Rita","family":"Ortolano","sequence":"additional","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Lanari","sequence":"additional","affiliation":[{"name":"Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, via Massarenti, 11, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ymgme.2007.06.007","article-title":"Glycogen Storage Disease Type IX: High Variability in Clinical Phenotype","volume":"92","author":"Beauchamp","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"138","DOI":"10.5223\/pghn.2015.18.2.138","article-title":"Clinical, Biochemical, and Genetic Characterization of Glycogen Storage Type IX in a Child with Asymptomatic Hepatomegaly","volume":"18","author":"Kim","year":"2015","journal-title":"Pediatr. Gastroenterol. Hepatol. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/s41436-018-0364-2","article-title":"Diagnosis and Management of Glycogen Storage Diseases Type VI and IX: A Clinical Practice Resource of the American College of Medical Genetics and Genomics (ACMG)","volume":"21","author":"Kishnani","year":"2019","journal-title":"Genet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/s41525-025-00527-y","article-title":"PHKA1-Associated Phosphorylase Kinase Deficiency: A Monogenic Disorder of Exercise Intolerance and Myalgia","volume":"10","author":"Koch","year":"2025","journal-title":"npj Genom. Med."},{"key":"ref_5","first-page":"417","article-title":"Identification of a Novel Mutation in the PHKA2 Gene in a Child with Liver Cirrhosis","volume":"35","author":"Beyzaei","year":"2022","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/MPG.0b013e31823276ea","article-title":"Glycogen Storage Disease Type IX: Novel PHKA2 Missense Mutation and Cirrhosis","volume":"55","author":"Johnson","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1136\/jmg.37.5.376","article-title":"Phosphorylase Kinase Deficient Liver Glycogenosis: Progression to Cirrhosis in Infancy Associated with PHKG2 Mutations (H144Y and L225R)","volume":"37","author":"Burwinkel","year":"2000","journal-title":"J. Med. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1203\/01.PDR.0000088069.09275.10","article-title":"Severe Phenotype of Phosphorylase Kinase-Deficient Liver Glycogenosis with Mutations in the PHKG2 Gene","volume":"54","author":"Burwinkel","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s004390050715","article-title":"Variability of Biochemical and Clinical Phenotype in X-Linked Liver Glycogenosis with Mutations in the Phosphorylase Kinase PHKA2 Gene","volume":"102","author":"Burwinkel","year":"1998","journal-title":"Hum. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1002\/aur.2486","article-title":"Autism: Screening of Inborn Errors of Metabolism and Unexpected Results","volume":"14","author":"Okur","year":"2021","journal-title":"Autism Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117391","DOI":"10.1016\/j.jns.2021.117391","article-title":"A Novel PHKA1 Mutation Associating Myopathy and Cognitive Impairment: Expanding the Spectrum of Phosphorylase Kinase b (PhK) Deficiency","volume":"424","author":"Bisciglia","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Candela, E., Montanari, G., Zanaroli, A., Baronio, F., Ortolano, R., Biasucci, G., and Lanari, M. (2025). Understanding Glycogen Storage Disease Type IX: A Systematic Review with Clinical Focus-Why It Is Not Benign and Requires Vigilance. Genes, 16.","DOI":"10.3390\/genes16050584"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Montanari, G., Candela, E., Baronio, F., Ferrari, V., Biasucci, G., Lanari, M., and Ortolano, R. (2025). Early-Onset Inherited Metabolic Diseases: When Clinical Symptoms Precede Newborn Screening-Insights from Emilia-Romagna (Italy). Children, 12.","DOI":"10.3390\/children12040464"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s13023-024-03274-y","article-title":"Short and Long-Term Acceptability and Efficacy of Extended-Release Cornstarch in the Hepatic Glycogen Storage Diseases: Results from the Glyde Study","volume":"19","author":"Weinstein","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/cge.12280","article-title":"Whole Exome Sequencing Unravels Disease-Causing Genes in Consanguineous Families in Qatar","volume":"86","author":"Fahiminiya","year":"2014","journal-title":"Clin. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1515\/jpem-2019-0603","article-title":"Variability of Clinical and Biochemical Phenotype in Liver Phosphorylase Kinase Deficiency with Variants in the Phosphorylase Kinase (PHKG2) Gene","volume":"33","author":"Waheed","year":"2020","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Shao, Y., Li, T., Jiang, M., Xu, J., Huang, Y., Li, X., Zheng, R., and Liu, L. (2022). A Very Rare Case Report of Glycogen Storage Disease Type IXc with Novel PHKG2 Variants. BMC Pediatr., 22.","DOI":"10.1186\/s12887-021-03055-7"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Karande, I.S., Boulter, E., Queit, L., and Balasubramaniam, S. (2016). Structured Dietary Management Dramatically Improves Marked Transaminitis, Metabolic and Clinical Profiles in Glycogen Storage Disease Type IXa. J. Inborn Errors Metab. Screen., 4.","DOI":"10.1177\/2326409816682766"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1515\/jpem-2021-0278","article-title":"Expected or Unexpected Clinical Findings in Liver Glycogen Storage Disease Type IX: Distinct Clinical and Molecular Variability","volume":"35","author":"Okur","year":"2022","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_21","first-page":"40","article-title":"Male Inheritance of X-Linked Liver Glycogenosis from an Undiagnosed Maternal Grandfather in a Chinese Pedigree: A Report of Two Cases","volume":"4","author":"Li","year":"2021","journal-title":"J. Bio-X Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e14839","DOI":"10.1111\/ped.14839","article-title":"A Novel PHKA2 Variant in a Japanese Boy with Glycogen Storage Diseases Type IXa","volume":"64","author":"Mori","year":"2022","journal-title":"Pediatr. Int."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Estrada, S.C. (2020). Glycogen Storage Disease IXa in a 9-Year-Old Filipino Boy with Short Stature: A Case Report. Acta Medica Philipp., 54.","DOI":"10.47895\/amp.v54i4.1930"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.dld.2020.04.017","article-title":"Liver Histology in Children with Glycogen Storage Disorders Type VI and IX","volume":"53","author":"Degrassi","year":"2021","journal-title":"Dig. Liver Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ymgme.2013.12.008","article-title":"Variability of Disease Spectrum in Children with Liver Phosphorylase Kinase Deficiency Caused by Mutations in the PHKG2 Gene","volume":"111","author":"Bali","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ymgme.2013.03.009","article-title":"Aggressive Therapy Improves Cirrhosis in Glycogen Storage Disease Type IX","volume":"109","author":"Tsilianidis","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e17775","DOI":"10.1097\/MD.0000000000017775","article-title":"Mutation in PHKA2 Leading to Childhood Glycogen Storage Disease Type IXa: A Case Report and Literature Review","volume":"98","author":"Zhu","year":"2019","journal-title":"Medicine"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fu, J., Wang, T., and Xiao, X. (2019). A Novel PHKA2 Mutation in a Chinese Child with Glycogen Storage Disease Type IXa: A Case Report and Literature Review. BMC Med. Genet., 20.","DOI":"10.1186\/s12881-019-0789-8"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1515\/jpem-2017-0170","article-title":"PHKG2 Mutation Spectrum in Glycogen Storage Disease Type IXc: A Case Report and Review of the Literature","volume":"31","author":"Li","year":"2018","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Beyzaei, Z., Ezgu, F., Geramizadeh, B., Alborzi, A., and Shojazadeh, A. (2021). Novel Mutations in the PHKB Gene in an Iranian Girl with Severe Liver Involvement and Glycogen Storage Disease Type IX: A Case Report and Review of Literature. BMC Pediatr., 21.","DOI":"10.1186\/s12887-021-02648-6"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13256-023-04295-0","article-title":"Report of an Iranian Child with Chronic Abdominal Pain and Constipation Diagnosed as Glycogen Storage Disease Type IX: A Case Report","volume":"18","author":"Zamanfar","year":"2024","journal-title":"J. Med. Case Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100493","DOI":"10.5409\/wjcp.v13.i4.100493","article-title":"Molecular Profiles and Long-Term Outcomes of Thai Children with Hepatic Glycogen Storage Disease in Thailand","volume":"13","author":"Vanduangden","year":"2024","journal-title":"World J. Clin. Pediatr."},{"key":"ref_33","first-page":"63","article-title":"Clinical and Molecular Variability in Patients with PHKA2 Variants and Liver Phosphorylase b Kinase Deficiency","volume":"37","author":"Bali","year":"2017","journal-title":"JIMD Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ymgme.2014.09.005","article-title":"The Natural History of Glycogen Storage Disease Types VI and IX: Long-Term Outcome from the Largest Metabolic Center in Canada","volume":"113","author":"Roscher","year":"2014","journal-title":"Mol. Genet. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.gene.2017.06.026","article-title":"Clinical and Genetic Characteristics of 17 Chinese Patients with Glycogen Storage Disease Type IXa","volume":"627","author":"Zhang","year":"2017","journal-title":"Gene"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.ymgme.2011.08.021","article-title":"Common Mutation in the PHKA2 Gene with Variable Phenotype in Patients with Liver Phosphorylase b Kinase Deficiency","volume":"104","author":"Achouitar","year":"2011","journal-title":"Mol. Genet. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1186\/s13023-024-03488-0","article-title":"Glycogen Storage Disorder Types IX: The Mutation Spectrum and Ethnic Distribution","volume":"19","author":"Geramizadeh","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1212\/WNL.0b013e31824365f9","article-title":"Muscle Phosphorylase Kinase Deficiency: A Neutral Metabolic Variant or a Disease?","volume":"78","author":"Preisler","year":"2012","journal-title":"Neurology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1212\/01.wnl.0000289190.66955.67","article-title":"Is Muscle Glycogenolysis Impaired in X-Linked Phosphorylase b Kinase Deficiency?","volume":"70","author":"Schelhaas","year":"2008","journal-title":"Neurology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/BF01799498","article-title":"The Long-Term Outcome of Patients with Glycogen Storage Diseases","volume":"13","author":"Smit","year":"1990","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1023\/A:1024071328772","article-title":"Characteristic Growth Pattern in Male X-Linked Phosphorylase-b Kinase Deficiency (GSD IX)","volume":"26","author":"Schippers","year":"2003","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1007\/BF00441207","article-title":"Growth and Endocrine Changes in the Hepatic Glycogenoses","volume":"138","author":"Dunger","year":"1982","journal-title":"Eur. J. Pediatr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1007\/s42000-025-00712-9","article-title":"Glucose Dynamics in Glycogen Storage Disease Type IXa with Novel PHKA2 Variants: Insights from Our Experience and a Comprehensive Review of the Disease Spectrum","volume":"24","author":"Baronio","year":"2025","journal-title":"Hormones"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/5\/648\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:42:43Z","timestamp":1778056963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/5\/648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":43,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["children13050648"],"URL":"https:\/\/doi.org\/10.3390\/children13050648","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]}}}