Rapid Genetic Analysis in Congenital Hyperinsulinism

<i>Backgound:</i> In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline <i>ABCC8</i> or <i>KCNJ11 </i>mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous <i>ABCC8</i> and<i> KCNJ11</i> mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. <i>Methods:</i> In 4 patients, a rapid genetic analysis of the <i>ABBC8</i> and <i>KCNJ11</i> genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. <i>Results:</i> Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal <i>KCNJ11 </i>mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous <i>ABBC8</i> mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. <i>Conclusion:</i> A rapid analysis of the entire <i>ABBC8</i> and <i>KCNJ11</i> genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations.