tal or early-childhood insulin-dependent diabetes and epiphyseal dysplasia. Other clinical features that show variability among WRScases include mental retardation, hepatic and kidney dysfunction, cardiac abnormalities, exocrine pancreatic dysfunction, and neutropenia.Data on the epidemiology of WRS are limited, and the latest literature review on the subject suggested that less than 60 of WRS cases were reported worldwide [5–7]. However, the condition has been recently found to be the commonest genetic cause of PNDM in consanguineous families and in the Arab population .
In our case we couldnot’t find any confirmation of consanguineous marriage. Our patients were foundto be homozygous for a novel EIF2AK3 missense mutation p.G1010V has not been reported previously. But it is likely to a pathogenic since this glycine residue is highly conserved across species and a different mutation at this codon, p. G1010D has been identified by this laboratory in 2 patients with Wolcott-Rallison syndrome.
There are only few case reports of the Wolcott-Rallison syndrome in which the clinical presentation includes recurrent infections, renal insuffiency, neutropenia, growth and developmental retardation, osteopenia, multiple epiphyseo-metaphyseal dysplasia, and exocrine pancreas insuffiency as common features [5,9]. Episodes of Acute Liver Failure are typical for this syndrome.
Another specific features of Wolcott-Rallison syndrome is bone dysplasia .The multiple epiphyseal dysplasia associated withWRS characteristically affects the long bones, pelvis andvertebrae. Osteoporosis has also been described in association with WRS in some patients .
Genetic counselling, molecular analysis and sequencing, electrophysiological analysis and antenatal history can help in confirmation ofthe right diagnosis. Patients need managment with insulin and appropriate treatment for other associated conditions.Early genetic verification of the syndrome can be useful for individualized medical support of the patients and preventing early mortality by providing multiorgan transplantation, for example .
WRS should be suspected in any infant who presents with permanent neonatal diabetes associated with episodes of acute liver failure. Molecular genetic testing confirms the diagnosis. Early diagnostics is recommended in order to ensure rapid intervention for episodes of hepatic failure, which is the most life threatening complication.
We thank Drs. Kachor L.A., Sichkaruk L.V. and Globa Y.V. for providing clinical information and blood samples of the WRS patient. We thank the Exeter University Laboratory, UK, for genetic identification of diagnosis.
The study was presented: 55th ESPE annual meeting, 10-12 September, Paris, France
Patient’s consent for publication has been granted
Contribution of authors must be listed on a separate form.
The authors contributed equally to this article. They read and approved the final version of the manuscript.
The authors declare that they have no competing interests
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8. Ab