Genotype and phenotype analysis of a cohort of patients with congenital hyperinsulinism based on DOPA-PET CT scanning.

Congenital hyperinsulinism (CHI) is a clinically, genetically, and morphologically heterogeneous disorder. 18F DOPA-PET CT scanning greatly improves its clinical outcome. Here, we presented the first Chinese 18F DOPA-PET CT scanning-based CHI cohort highlighting the variable ethic clinical phenotypes and genotypes. Fifty CHI patients were recruited. Median age at presentation was 2 days. Median fasting time was 2 h. Mean insulin level was 25.6 µIU/ml. Fifty-two percent of patients were diazoxide-unresponsive with significantly shorter fasting tolerance time and higher serum insulin level compared with the responsive patients. Seventy-four percent of patients experienced at least one adverse drug reaction. Tremendously increased focal lesions (32%) were detected and 75% of them were cured through surgery. Thirty-one nucleotide sequence changes were identified in 48% patients. Four novel variants (Q608X, Q1347X, Q289X, F1489S) in ABCC8 gene and 2 novel variants (G132A, V138E) in KCNJ11 gene were detected. Of the variants, 87.1% harbored in ABCC and KCNJ11 genes. T1042Qfs*75 in ABCC8 gene was the most common mutation.Conclusion: Highly increased portion of focal lesion was presented in Chinese CHI patients compared with that of the previous reports. Intolerance to diazoxide was much more evident in Chinese or East Asian than other populations. Certain hotspot mutations harbored in Chinese CHI patients. What is Known: • 18F DOPA-PET CT scanning can provide informative guidance for surgical procedure when medical therapy is not well responded in CHI patients. What is New: • Intolerance to diazoxide is much more evident in Chinese and East Asian CHI patients compared with the other ethnic populations. • Novel mutations were detected in ABCC8 and KCNJ11 gene. Hotspot mutations such as T1042Qfs*75, I1511K, E501K, G111R in ABCC8 gene, and R34H in KCNJ11 gene are predominantly responsible for Chinese CHI patients.

Diagnostic accuracy of [¹8F]-fluoro-L-dihydroxyphenylalanine positron emission tomography scan for persistent congenital hyperinsulinism in Japan.

OBJECTIVE: We aimed to elucidate the accuracy and limitations of [(18)F]-fluoro-L-dihydroxyphenylalanine ([(18) F]DOPA) positron emission tomography (PET) for Japanese patients with congenital hyperinsulinism. Although [(18)F]DOPA PET is reported to be useful for precisely localizing the focal form of congenital hyperinsulinism, previous reports are mostly from European and North American centres. PATIENTS: Seventeen Japanese infants with congenital hyperinsulinism. MEASUREMENTS: [(18)F]DOPA PET studies were carried out, and the results were assessed by simple inspection or by a quantitative measurement termed the 'Pancreas Percentage', which expresses the uptake of the head, body or tail of the pancreas as a percentage of the total maximum standardized uptake value of the whole pancreas. The results were compared with those of other studies, including genetic analysis and histology. RESULTS: By simple inspection, when a single focal uptake was obtained, the localization and histology were correct in all cases that underwent pancreatectomy. However, the overall results were consistent with the molecular diagnosis and histology in only 7/17 and 6/12 patients, respectively. The inaccuracy of PET studies by inspection was because of elevated background uptake that mimicked a diffuse or multifocal appearance. The accuracy improved substantially using the Pancreas Percentage; it was consistent with the molecular diagnosis and histology in 10/17 and 9/12 patients, respectively. CONCLUSIONS: In contrast to the results of previous reports, [(18)F]DOPA PET appears to be less efficient for diagnosing Japanese patients with congenital hyperinsulinism. However, the diagnostic accuracy is substantially improved when this technique is combined with the Pancreas Percentage.