ESPE Abstracts (2014) 82 P-D-2-3-351

Wolcott-Rallison Syndrome: New Mutations and Report of Two Cases

Erdal Erena, Esra Deniz Papatya Cakira, Sefika Elmas Bozdemirb, Solmaz Celebib, Cécile Julierc, Halil Saglama & Omer Tarima


aDepartment of Pediatric Endocrinology, Medical Faculty, Uludag University, Bursa, Turkey; bDepartment of Pediatric Infection Diseases, Medical Faculty, Uludag University, Bursa, Turkey; cUMR-S958 Inserm Faculte de Medicine Villemin 10 avenue de Verdun, Paris, France


Background: Wolcott-Rallison syndrome (WRS) is a rare, autosomal recessive disease and characterized by early-onset diabetes, spondyloepiphyseal dysplasia, short stature, osteopenia, acute liver failure, and neurological deficit. It results from mutation in a gene of the eukaryotic translation initiation factor 2-α kinase 3 (EIF2AK3).

Objective and hypotheses: We report two WRS patients diagnosed in infantile period.

Method: PCR techniques were used to amplify the 17 exons of the EIF2AK3 gene and DNA direct assay techniques were used for gene mutation analysis. Patient 1: a boy was admitted to our clinic for diabetic ketoacidosis at the age of 15 months. Liver biopsies were performed due to elevated transaminases were consistent with chronic hepatitis. At the age of 8.5 years, height 109 cm (−3.82 SDS), weight 21.6 kg (−1.6 SDS), genu valgum deformity, difficulty in walking and running were remarkable on physical examination. Patient 2, a boy was diagnosed diabetes at the age of 17 months. At 7 years of age, intracranial abscess developed which was successfully treated with posaconasole and hyperbaric oxygen. At the age of 9.5 years, physical examination showed height of 103 cm (−5.2 SDS), weight of 16.1 kg (−5.6 SDS), genu valgum deformity, difficulty in walking and running.

Results: Two new homozygous mutations (E926K and K939R) in patient 1, and internal deletion in the EIF2AK3 gene which has never been reported in patient 2 were identified.

Conclusion: Major skeletal abnormalities of WRS are osteoporosis/osteopenia, thoracolumbar kyphosis, and bowing of the femur. In addition, pancreas exocrine insufficiency, hypothyroidism, and various central nervous system anomalies have been reported. WRS should be suspected in any child who presents with permanent, nonimmune neonatal/infantile diabetes associated with skeletal dysplasia, short stature, episodes of acute liver failure, or pancytopenia, diabetes associated with skeletal dysplasia, short stature, episodes of acute liver failure, or pancytopenia.

Article tools

My recent searches

No recent searches.