title: Recurrent Hepatitis in Two Iranian Children: A Novel (Q166R) Mutation in EIF2AK3 Leading to Wolcott-Rallison Syndrome.
abstract: Early-onset diabetes, liver dysfunction, growth retardation, spondyloepiphyseal dysplasia, and tendency to skeletal fractures due to osteopenia are characteristics of Wolcott-Rallison syndrome (WRS). Eukaryotic translation initiation factor 2α kinase (EIF2AK3) is the only known gene, which is responsible for this rare autosomal recessive disorder. Here, we report two siblings a girl and a boy with diabetes mellitus (DM) who presented in one and two months of age respectively. Recurrent self-limiting hepatitis developed later, and severe hepatic failure resulted in death of the first child. The second child visited was a 7.75 year old boy who had spondyloepiphyseal dysplasia and subclinical hypothyroidism besides DM and recurrent hepatitis. We suggested WRS for this patient, and it was confirmed by identification of a novel homozygous missense mutation (Q166R) in exon 3 of the EIF2AK3 gene. The aim of this report is to remind the possibility of WRS in isolated neonatal diabetes; while, the other clinical manifestations of this syndrome including its major symptom of recurrent hepatitis may appear later.
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, IR Iran ; Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, IR Iran ; Ali-Asghar Children Hospital, Iran University of Medical Sciences, Tehran, IR Iran.
authors.forename: Babak
authors.initials: B
authors.lastname: Behnam
authors.forename: Marjan
authors.initials: M
authors.lastname: Shakiba
authors.forename: Ali
authors.initials: A
authors.lastname: Ahani
authors.forename: Maryam
authors.initials: M
authors.lastname: Razzaghy Azar
keywords: Diabetes Mellitus; Spondyloepiphyseal Dysplasia; Wolcott-Rallison Syndrome
references.citation: J Clin Res Pediatr Endocrinol. 2012 Jun;4(2):101-3
references.pmid: 22672868
references.citation: Clin Genet. 1996 Mar;49(3):152-5
references.pmid: 8737981
references.citation: Eur J Pediatr. 1982 Mar;138(2):120-9
references.pmid: 7094931
references.citation: Exp Diabetes Res. 2012;2012:958169
references.pmid: 22701473
references.citation: Pediatr Diabetes. 2011 May;12(3 Pt 1):187-91
references.pmid: 21518408
references.citation: Nat Genet. 2000 Aug;25(4):406-9
references.pmid: 10932183
references.citation: J Med Genet. 2003 Sep;40(9):685-9
references.pmid: 12960215
references.citation: J Clin Endocrinol Metab. 2009 Nov;94(11):4162-70
references.pmid: 19837917
references.citation: Biol Cell. 2013 May;105(5):219-233
references.pmid: 23398201
references.citation: Diabetes. 2002 Jul;51(7):2301-5
references.pmid: 12086964
references.citation: J Pediatr. 1972 Feb;80(2):292-7
references.pmid: 5008828
references.citation: Ann Saudi Med. 2001 Jan-Mar;21(1-2):73-4
references.pmid: 17264596
references.citation: J Pediatr Endocrinol Metab. 2011;24(3-4):181-4
references.pmid: 21648287
references.citation: Zhonghua Er Ke Za Zhi. 2011 Apr;49(4):301-5
references.pmid: 21624209
references.citation: Orphanet J Rare Dis. 2010 Nov 04;5:29
references.pmid: 21050479
references.citation: Endocrinology. 2013 Mar;154(3):1055-68
references.pmid: 23407450
references.citation: Clin Dysmorphol. 1995 Jul;4(3):227-33
references.pmid: 7551159
references.citation: Diabetes. 2004 Jul;53(7):1876-83
references.pmid: 15220213
references.citation: J Med Genet. 1998 Apr;35(4):288-92
references.pmid: 9598721
references.citation: Hepatol Res. 2013 Jan;43(1):51-64
references.pmid: 23332087
references.citation: Diabetes Metab Res Rev. 2010 Nov;26(8):611-21
references.pmid: 20922715