TY - JOUR
T1 - Liver fibrosis during clinical ascertainment of glycogen storage disease type III
T2 - a need for improved and systematic monitoring
AU - Halaby, Carine A.
AU - Young, Sarah P.
AU - Austin, Stephanie
AU - Stefanescu, Ela
AU - Bali, Deeksha
AU - Clinton, Lani K.
AU - Smith, Brian
AU - Pendyal, Surekha
AU - Upadia, Jariya
AU - Schooler, Gary R.
AU - Mavis, Alisha M.
AU - Kishnani, Priya S.
N1 - Publisher Copyright:
© 2019, American College of Medical Genetics and Genomics.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - GSD III liver
KW - cirrhosis
KW - hepatocellular fibrosis
KW - urinary glucose tetrasaccharide
UR - http://www.scopus.com/inward/record.url?scp=85068445194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068445194&partnerID=8YFLogxK
U2 - 10.1038/s41436-019-0561-7
DO - 10.1038/s41436-019-0561-7
M3 - Article
C2 - 31263214
AN - SCOPUS:85068445194
SN - 1098-3600
VL - 21
SP - 2686
EP - 2694
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 12
ER -