 in consanguineous families. In patients with genetically diagnosed Wolcott-Rallison syndrome, 23 (88%) of 26 patients tested within 3 months from the diagnosis had an isolated diabetes, compared with three (17%) of 18 patients referred later (>4 years; p<0·0001), in whom skeletal and liver involvement was common.
We present the fist case reported from Ukraine of a child diagnosed with permanent NDM resulting from a EIF2AK3 gene missense mutation of exon 15 (Wolcott-Rallison Syndrome).Confirmation of the gene mutation EIF2AK3 presence in our patient was done by the laboratoryof Exeter University, UK.
A diabetic boy was admitted for usual check up to the Endocrinology Department of Ternopil Regional Childrens’ Hospital.
From anamnesis: he is full-term child from second physiological pregnancy and delivery, birth weight 2,500 g. Neonatal period was usual. Family history is unremarkable. In the age of 6 weeks he was hospitalized due to moderate dehydration and intoxication syndromes without vomiting or diarrhea. Capillary blood glucose was 22 mmol/l (N=3,3-5,5) [396 mg/dl], Hb1Ac = 9.662 %.(N = 4,8-5,9),C-peptide = 0,27 ng/ml, (N = 0,9-7,10) and manifestation of NDM had been diagnosed. General condition of the child quickly improved due tothe combined insulin therapy. By genetic DNA analysis of parents and child blood novel EIF2AK3 gene missense mutation of exon 15 was revealed by Sanger sequencing which confirmed the clinical diagnosis of Wolcott-Rallison syndrome. The analysis of all other known neonatal diabetes genes did not identify a pathogenic mutation.
The child grew and developed properly on a regular basis-bolus insulin therapy in adaily dose of 0.36 U/kg body weight. The course of diabetes was stable, glycosylated hemoglobin per year observation was 8.2–8.5%.
In the age of 1 year the boy was hospitalized in the intensive care unit due to a grave general condition: fever, intoxication, lethargy, anorexia, jaundice, generalized edema, hepatomegaly, oliguria, acholic stool. A blood test revealed: mild hypochromic anemia, hypoproteinemia, normal urea and creatininelevel, high transaminases, hyperbilirubinemia, hypokaliemia. Hepatitis markers were negative. Glucose and ketone bodies were absent in the urine analyses. HbA1c was 8.6%.Hepatomegaly, portions of free liquid in abdominal and pericardial cavity, hydrocephaly were revealed at the ultrasound examination. Based on these signs and symptoms acute liver failure was diagnosed.
After the intensive care for a month with insulin therapy, parenteral nutrition, repeated blood transfusions, albumin infusion, detoxification therapy, forced diuresis,correction of electrolyte balance,the child’s condition improved.
The mother complained of lameness of left leg in the child, which had become more intensive and persistent during the previous months. The x-ray examination confirmed the hypoplasia of the left hip joint.Bone dysplasia is one of the typical signs of Wolcott-Rallison Syndrome. The child was discharged from the hospital in a satisfactory condition.
In the age of two years, the child was hospitalized with an acute respiratory infection and sudden aggressive development of the liver failure which was fatal to the child despite of intensive care.
Most of all mutations at NDM are normally caused by intrauterine growth restriction, meaning these mutations usually occur during the first trimester. Early signs and symptoms in these infants include low weight, hyperglycemia, seizures, developmental delay and abnormal cognitive function. In the case of Wolcott-Rallison Syndrome, the children also do present with above stated signs but their distinctive features are osteopenia, bone dysplasia and, in most cases, a series of hepatic failures and splenomegaly. Although skeletal dysplasia is a main feature, it is usually noticed in patients in the period from 3 to 6years old.
Wolcott-Rallison syndrome is an extremely rare condition worldwide. It was named after Drs Wolcott and Rallison, who first described this syndrome in three affected siblings . It associates permanent neona