Novel CYP11B2 mutation causing aldosterone synthase (P450c11AS) deficiency.

UNLABELLED: Aldosterone synthase (P450c11AS) deficiency is a rare autosomal recessive disorder, presenting with severe salt-losing in early infancy. It is caused by inactivating mutations of the CYP11B2 gene. Here, we describe three unrelated Asian patients who have clinical and hormonal features compatible with aldosterone synthase deficiency and identify their CYP11B2 mutations. Patient 1 was a Thai female infant. Patient 2 was an Indian boy, and patient 3 was a Thai male infant. All subjects presented at the age of 1-2 months with diarrhea, failure to thrive, and severe dehydration. Their plasma electrolytes showed hyponatremia, hyperkalemia, and acidosis. All patients had normal cortisol response and had elevated plasma renin activity with low aldosterone levels. The entire coding regions of the CYP11B2 gene were amplified by polymerase chain reaction and sequenced. Patient 1 was homozygous for a previously described mutation, p.T318M. Patient 2 was homozygous for a novel c.666delC mutation inherited from both parents resulting in p.223F>Sfsx295. No CYP11B2 mutation was detected in patient 3. CONCLUSIONS: We report the first CYP11B2 defects in Southeast Asian families responsible for aldosterone synthase deficiency and identified a novel CYP11B2 mutation. However, the affected gene(s) responsible for primary hypoaldosteronism other than CYP11B2 remain to be determined.

Obesity, metabolic syndrome, and insulin dynamics in children after craniopharyngioma surgery.

INTRODUCTION: Children after craniopharyngioma surgery often develop rapid weight gain and hyperphagia. We investigate the metabolic syndrome features, risk factors, and the insulin dynamics in these patients. MATERIALS AND METHODS: Standard oral glucose tolerance tests (OGTT) were performed in 12 subjects, aged 7.7-18.1 years, after surgical removal of craniopharyngioma and their healthy age-, sex-, body mass index-, and pubertal stage-matched controls. Blood samples were obtained for measurement of levels of plasma glucose, insulin, lipids, liver enzymes, baseline hormonal profiles with calculation of insulin secretion, and insulin sensitivity indices derived from OGTT. RESULTS AND DISCUSSION: Nine of 12 subjects were severely obese. All patients exhibited significant weight gain after surgery. The waist to hip ratio was higher in subjects compared to controls (P = 0.023). Subjects had higher fasting triglycerides (P = 0.019) and lower HDL/total cholesterol ratio (P = 0.012). Five of 12 subjects met the criteria for the metabolic syndrome, compared with one of 12 in controls. One patient had prediabetes and another patient had overt type 2 diabetes. Six of 12 subjects had nonalcoholic steatohepatitis. No significant risk factors were found between each group of patients with and without the metabolic syndrome. There were no differences of insulin secretion and insulin sensitivity indices between craniopharyngioma and control subjects. CONCLUSION: Children after craniopharyngioma surgery are at risk of rapid weight gain and the development of metabolic syndrome. Further studies to better understand the mechanism are required to design effective treatment and prevention.