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

Abstract

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.

Hypoketotic hypoglycemia in citrin deficiency: a case report

“…The blood ketone levels might be relatively low in the hypoglycemic situation. Moreover, another study describing ketotic hypoglycemia revealed a CD case with hypoglycemic convulsion [11], while blood ketone levels (total ketone body level was 1.8 mM) were certainly elevated but relatively low for the predicted compensatory change (expected total ketone body level was > 5 mM) [8]. This result should be considered as insufficient ketosis with hypoglycemia.…”

Hypoglycemic attacks and growth failure are the most common manifestations of citrin deficiency after 1 year of age

“…On the basis of our findings and those of previous studies, we should consider citrin deficiency when individuals experience severe hypoglycemia in childhood. 17,18 This report included nine patients with symptomatic hypoglycemia, which might indicate failed glucose homeostasis due to citrin deficiency. These attacks were recorded during a catabolic state after 1 year of life but never in infancy, except in neonates.…”

“…Some case reports have shown that patients in childhood with citrin deficiency exhibit fatigue, hypoglycemia, hyperlipidemia, growth failure, or liver dysfunction. 5,[15][16][17][18] Nutritional analysis in patients revealed that they have peculiar food preferences, such as a preference for lipidrich or protein-rich foods and an aversion to highcarbohydrate foods, which might compensate for the metabolic failure caused by citrin deficiency. 19 Okano et al reported that citrin-deficient patients had lower fatigue and quality of life scores during the adaptation and compensation stages than controls.…”

A Case Report: Can Citrin Deficiency Lead to Hepatocellular Carcinoma in Children?

“…Current treatment strategies for FTTDCD include diet therapy (low carbohydrate and high protein and fat) and supplements (e.g., administration of sodium pyruvate and/or MCT) (25). A case reported by Otsuka et al (26) showed MCT therapy can prevent the onset of hypoglycemia during the so-called apparently healthy period. In addition, it is speculated that long-term MCT supplementation may prevent a complication of HCC by suppressing the Wnt/β-catenin pathway (27).…”