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Wolcott-Rallison syndrome (WRS) is a rare, autosomal recessive genetic disorder associated with permanent neonatal diabetes mellitus (PNDM) and multiple epiphyseal dysplasia (MED). Prognosis is generally very poor and often results in early death thus very few cases have been reported and studied with fewer than 60 appearing in literature. The disorder is often observed in patients with a mutation in the EIF2AK3 gene which codes for a translation initiation factor kinase. In consanguineous families WRS has been identified as one of the most common genetic causes of early onset diabetes. Patients will often show obvious physical symptoms of the disorder including abnormal bone structure and teeth decolorization or absence.

Diagnosis
Diabetic infants are often diagnosed with WRS following episodes of acute liver failure and skeletal dysplasia. Family history is often taken into account due to the high rates of occurence in consanguineous populations, as well as prior sibling fatalities due to diabetes. Instances of the disease are likely underrepresented due to early death prior to diagnosis and limited health care in commonly afficted countries. Genetic diagnosis often looks for mutations in the EIF2AK3 gene and identification of malfunctions in this protein are a typical deciding factor during differential diagnosis.

Symptoms
Due to high instances of early fatality in patients with WRS most studies have been performed post-mortem. Studies have shown that death normally occurs due to acute liver failure following flu-like symptoms. Autopsy findings have indicated hemorrhagic ascites in the stomach of patients and abnormally enlarged and discoloured livers.

On the surface patients can be identified by short stature and difficulties when learning how to walk. Limited joint movement in the shoulders, hips, elbows and wrists are the result of skeletal deformities that progress with age until growth ceases around the age of 10. Dental caries are also prevalent along with other dental deformities. Symptoms of diabetes are also observed.

Treatment
Genetic counselling is recommended to any parents with a previous diagnosis of WRS. Diabetic symptoms can be closely monitored and treated with use of an insulin pump. High degrees of insulin control over blood glucose should be avoided due to the young age of patients as this can lead to hypoglycemic episodes. Therapy for bone dysfunctions is also suggested. Non-essential medicines and anaesthetics should be avoided to avoid risk of liver failure. Liver, pancreas and double kidney transplants have also been successfully performed in extreme manifestations of the disease.