Carine A Halaby1, Sarah P Young1, Stephanie Austin1, Ela Stefanescu1, Deeksha Bali1, Lani K Clinton2, Brian Smith3, Surekha Pendyal1, Jariya Upadia1, Gary R Schooler4, Alisha M Mavis5, Priya S Kishnani6. 1. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. 2. Department of Pathology, Duke University Medical Center, Durham, NC, USA. 3. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. 4. Department of Radiology, Duke University Medical Center, Durham, NC, USA. 5. Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. 6. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. priya.kishnani@duke.edu.
Abstract
PURPOSE: In glycogen storage disease type III (GSD III), liver aminotransferases tend to normalize with age giving an impression that hepatic manifestations improve with age. However, despite dietary treatment, long-term liver complications emerge. We present a GSD III liver natural history study in children to better understand changes in hepatic parameters with age. METHODS: We reviewed clinical, biochemical, histological, and radiological data in pediatric patients with GSD III, and performed a literature review of GSD III hepatic findings. RESULTS: Twenty-six patients (median age 12.5 years, range 2-22) with GSD IIIa (n = 23) and IIIb (n = 3) were enrolled in the study. Six of seven pediatric patients showed severe fibrosis on liver biopsy (median [range] age: 1.25 [0.75-7] years). Markers of liver injury (aminotransferases), dysfunction (cholesterol, triglycerides), and glycogen storage (glucose tetrasaccharide, Glc4) were elevated at an early age, and decreased significantly thereafter (p < 0.001). Creatine phosphokinase was also elevated with no significant correlation with age (p = 0.4). CONCLUSION: Liver fibrosis can occur at an early age, and may explain the decrease in aminotransferases and Glc4 with age. Our data outlines the need for systematic follow-up and specific biochemical and radiological tools to monitor the silent course of the liver disease process.
PURPOSE: In glycogen storage disease type III (GSD III), liver aminotransferases tend to normalize with age giving an impression that hepatic manifestations improve with age. However, despite dietary treatment, long-term liver complications emerge. We present a GSD III liver natural history study in children to better understand changes in hepatic parameters with age. METHODS: We reviewed clinical, biochemical, histological, and radiological data in pediatric patients with GSD III, and performed a literature review of GSD III hepatic findings. RESULTS: Twenty-six patients (median age 12.5 years, range 2-22) with GSD IIIa (n = 23) and IIIb (n = 3) were enrolled in the study. Six of seven pediatric patients showed severe fibrosis on liver biopsy (median [range] age: 1.25 [0.75-7] years). Markers of liver injury (aminotransferases), dysfunction (cholesterol, triglycerides), and glycogen storage (glucose tetrasaccharide, Glc4) were elevated at an early age, and decreased significantly thereafter (p < 0.001). Creatine phosphokinase was also elevated with no significant correlation with age (p = 0.4). CONCLUSION: Liver fibrosis can occur at an early age, and may explain the decrease in aminotransferases and Glc4 with age. Our data outlines the need for systematic follow-up and specific biochemical and radiological tools to monitor the silent course of the liver disease process.
Entities:
Keywords:
GSD III liver; cirrhosis; hepatocellular fibrosis; urinary glucose tetrasaccharide
Authors: Lindsay C Burrage; Simran Madan; Xiaohui Li; Saima Ali; Mahmoud Mohammad; Bridget M Stroup; Ming-Ming Jiang; Racel Cela; Terry Bertin; Zixue Jin; Jian Dai; Danielle Guffey; Milton Finegold; Sandesh Nagamani; Charles G Minard; Juan Marini; Prakash Masand; Deborah Schady; Benjamin L Shneider; Daniel H Leung; Deeksha Bali; Brendan Lee Journal: JCI Insight Date: 2020-02-27
Authors: Terry G J Derks; Fabian Peeks; Foekje de Boer; Marieke Fokkert-Wilts; Hubert P J van der Doef; Marius C van den Heuvel; Edyta Szymańska; Dariusz Rokicki; Patrick T Ryan; David A Weinstein Journal: J Inherit Metab Dis Date: 2020-12-21 Impact factor: 4.982
Authors: Sarah P Young; Aleena Khan; Ela Stefanescu; Andrea M Seifts; Ghada Hijazi; Stephanie Austin; Priya S Kishnani Journal: JIMD Rep Date: 2020-11-03
Authors: Irene J Hoogeveen; Foekje de Boer; Willemijn F Boonstra; Caroline J van der Schaaf; Ulrike Steuerwald; Anita J Sibeijn-Kuiper; Riemer J K Vegter; Johannes H van der Hoeven; M Rebecca Heiner-Fokkema; Kieran C Clarke; Pete J Cox; Terry G J Derks; Jeroen A L Jeneson Journal: J Inherit Metab Dis Date: 2020-09-07 Impact factor: 4.982
Authors: Alberto Molares-Vila; Alberte Corbalán-Rivas; Miguel Carnero-Gregorio; José Luís González-Cespón; Carmen Rodríguez-Cerdeira Journal: Int J Mol Sci Date: 2021-04-22 Impact factor: 5.923
Authors: Ghada Hijazi; Anna Paschall; Sarah P Young; Brian Smith; Laura E Case; Tracy Boggs; Sathya Amarasekara; Stephanie L Austin; Surekha Pendyal; Areeg El-Gharbawy; Kristen L Deak; Andrew J Muir; Priya S Kishnani Journal: Mol Genet Metab Rep Date: 2021-11-11