romic 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 neonatal 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 