TY - CHAP
T1 - Novel association of early onset hepatocellular carcinoma with transaldolase deficiency
AU - LeDuc, Charles A.
AU - Crouch, Elizabeth E.
AU - Wilson, Ashley
AU - Lefkowitch, Jay
AU - Wamelink, Mirjam M.C.
AU - Jakobs, Cornelis
AU - Salomons, Gajja S.
AU - Sun, Xiaoyun
AU - Shen, Yufeng
AU - Chung, Wendy K.
N1 - Publisher Copyright: © SSIEM and Springer-Verlag Berlin Heidelberg 2013.
PY - 2014
Y1 - 2014
N2 - We evaluated a family with a 16-month-old boy with cirrhosis and hepatocellular carcinoma and his 30-month-old brother with cirrhosis. After failing to identify a diagnosis after routine metabolic evaluation, we utilized a combination of RNA-Seq and whole exome sequencing to identify a novel homozygous p.Ser171Phe Transaldolase (TALDO1) variant in the proband, his brother with cirrhosis, as well as a clinically asymptomatic older 8-year-old brother. Metabolite analysis and enzymatic testing of TALDO1 demonstrated elevated ribitol, sedoheptitol, and sedoheptulose-7P, and lack of activity of TALDO1 in the three children homozygous for the p.Ser171Phe mutation. Our findings expand the phenotype of transaldolase deficiency to include early onset hepatocellular carcinoma in humans and demonstrate that, even within the same family, individuals with the same homozygous mutation demonstrate a wide range of phenotypes.
AB - We evaluated a family with a 16-month-old boy with cirrhosis and hepatocellular carcinoma and his 30-month-old brother with cirrhosis. After failing to identify a diagnosis after routine metabolic evaluation, we utilized a combination of RNA-Seq and whole exome sequencing to identify a novel homozygous p.Ser171Phe Transaldolase (TALDO1) variant in the proband, his brother with cirrhosis, as well as a clinically asymptomatic older 8-year-old brother. Metabolite analysis and enzymatic testing of TALDO1 demonstrated elevated ribitol, sedoheptitol, and sedoheptulose-7P, and lack of activity of TALDO1 in the three children homozygous for the p.Ser171Phe mutation. Our findings expand the phenotype of transaldolase deficiency to include early onset hepatocellular carcinoma in humans and demonstrate that, even within the same family, individuals with the same homozygous mutation demonstrate a wide range of phenotypes.
KW - Exome sequencing
KW - Glycogen storage disease
KW - Hepatocellular carcinoma
KW - Normal platelet count
KW - Urine organic acid
UR - http://www.scopus.com/inward/record.url?scp=84903385918&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/8904_2013_254
DO - https://doi.org/10.1007/8904_2013_254
M3 - Chapter
T3 - JIMD Reports
SP - 121
EP - 127
BT - JIMD Reports
PB - Springer
ER -