(Epi)genetic defects of MKRN3 are rare in Asian patients with central precocious puberty.

We sequenced MKRN3, the major causative gene of central precocious puberty in Western countries, in 24 Japanese or Chinese patients and examined the DNA methylation and copy-number statuses of this gene in 19 patients. We identified no (epi)genetic defects except for one previously reported mutation. These results, together with reports from Korea, indicate that MKRN3 defects are rare in Asian populations. The ethnic differences likely reflect Western country-specific founder mutations and the rarity of de novo mutations.

Effectiveness of Medium-Chain Triglyceride Oil Therapy in Two Japanese Citrin-Deficient Siblings: Evaluation Using Oral Glucose Tolerance Tests.

Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD+ ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis. The brother and sister underwent an oral glucose tolerance test (OGTT) at 10 and 7 yr of age, respectively. Blood glucose, ammonia, lactic acid, pyruvic acid, and insulin levels were monitored before starting the test, and then every 30 min. During this test, they maintained blood glucose levels until 180 min. At 210 min, they experienced vomiting, feeling ill, and decreased blood glucose levels (2.9 and 2.8 mmol/l in the brother and sister, respectively). The sister and brother recovered uneventfully by intravenous glucose injection. In a second OGTT, 4 months after medium-chain triglyceride (MCT) oil supplementation, they had no major symptoms and normal glucose levels were maintained, even after 240 min. Additionally, after MCT oil therapy, their food preference slightly changed as they started eating more carbohydrates. Our OGTT data suggest excess carbohydrate intake has adverse consequences in patients with citrin deficiency, including hypoglycemia after a few hours. MCT oil therapy may be effective in preventing such hypoglycemia and improving metabolic derangement, even during the so-called apparently healthy period.