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Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia ☆

View Article: PubMed Central - PubMed

ABSTRACT

Background: Citrin, encoded by SLC25A13, is a component of the malate-aspartate shuttle, which is the main NADH-transporting system in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually resolves within the first year of life. However, small numbers of adults with citrin deficiency develop hyperammonemic encephalopathy, adult-onset type II citrullinemia (CTLN2), which leads to death due to cerebral edema. Liver transplantation is the only definitive therapy for patients with CTLN2. We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. Citrin deficiency may impair the glycolysis in hepatocytes because of an increase in the cytosolic NADH/NAD+ ratio, leading to an energy shortage. MCT administration can provide energy to hepatocytes and was expected to have a good effect on CTLN2.

Methods: An MCT supplementation therapy under a low-carbohydrate formula was administered to five patients with CTLN2. Four of the patients had episodes of hyperammonemic encephalopathy, and one patient had postprandial hyperammonemia with no symptoms.

Results: One of the patients displaying hyperammonemic encephalopathy completely recovered with all normal laboratory findings. Others notably improved in terms of clinical and or laboratory findings with no hyperammonemic symptoms; however, the patients displayed persistent mild citrullinemia and occasionally had postprandial mild hyperammonemia most likely due to an irreversible change in the liver.

Conclusions: An MCT supplement can provide energy to hepatocytes and promote hepatic lipogenesis, leading to a reduction in the cytosolic NADH/NAD+ ratio. MCT supplementation under a low-carbohydrate formula could be a promising therapy for CTLN2 and should also be used to prevent CTLN2 to avoid irreversible liver damage.

No MeSH data available.


Diurnal change in blood ammonia in Case 2.The open circles, triangles and squares represent the levels of blood ammonia before treatment, at 14 days after treatment, and at 35 days after treatment, respectively.
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f0030: Diurnal change in blood ammonia in Case 2.The open circles, triangles and squares represent the levels of blood ammonia before treatment, at 14 days after treatment, and at 35 days after treatment, respectively.

Mentions: The patient was treated with a supplement of 45 mL of Macton oil under a low-carbohydrate formula (2220 cal a day; protein: fat: carbohydrate ratio was 16: 36: 48). The patient's condition improved, and there were no more episodes of encephalopathy. All abnormal biochemical findings, including postprandial hyperammonemia, were nearly normalized within seven months of treatment (Fig. 1, Supplementary Fig. 3, Supplementary Fig. 4, and Table 1). He had no deterioration even after a reduction of Macton oil to 30 mL/day at 10 months of the therapy. No signs of fatty liver were observed using abdominal ultrasonography after 26 months of therapy.


Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia ☆
Diurnal change in blood ammonia in Case 2.The open circles, triangles and squares represent the levels of blood ammonia before treatment, at 14 days after treatment, and at 35 days after treatment, respectively.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121258&req=5

f0030: Diurnal change in blood ammonia in Case 2.The open circles, triangles and squares represent the levels of blood ammonia before treatment, at 14 days after treatment, and at 35 days after treatment, respectively.
Mentions: The patient was treated with a supplement of 45 mL of Macton oil under a low-carbohydrate formula (2220 cal a day; protein: fat: carbohydrate ratio was 16: 36: 48). The patient's condition improved, and there were no more episodes of encephalopathy. All abnormal biochemical findings, including postprandial hyperammonemia, were nearly normalized within seven months of treatment (Fig. 1, Supplementary Fig. 3, Supplementary Fig. 4, and Table 1). He had no deterioration even after a reduction of Macton oil to 30 mL/day at 10 months of the therapy. No signs of fatty liver were observed using abdominal ultrasonography after 26 months of therapy.

View Article: PubMed Central - PubMed

ABSTRACT

Background: Citrin, encoded by SLC25A13, is a component of the malate-aspartate shuttle, which is the main NADH-transporting system in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually resolves within the first year of life. However, small numbers of adults with citrin deficiency develop hyperammonemic encephalopathy, adult-onset type II citrullinemia (CTLN2), which leads to death due to cerebral edema. Liver transplantation is the only definitive therapy for patients with CTLN2. We previously reported that a lactose (galactose)-restricted and medium-chain triglyceride (MCT)-supplemented formula is notably effective for patients with NICCD. Citrin deficiency may impair the glycolysis in hepatocytes because of an increase in the cytosolic NADH/NAD+ ratio, leading to an energy shortage. MCT administration can provide energy to hepatocytes and was expected to have a good effect on CTLN2.

Methods: An MCT supplementation therapy under a low-carbohydrate formula was administered to five patients with CTLN2. Four of the patients had episodes of hyperammonemic encephalopathy, and one patient had postprandial hyperammonemia with no symptoms.

Results: One of the patients displaying hyperammonemic encephalopathy completely recovered with all normal laboratory findings. Others notably improved in terms of clinical and or laboratory findings with no hyperammonemic symptoms; however, the patients displayed persistent mild citrullinemia and occasionally had postprandial mild hyperammonemia most likely due to an irreversible change in the liver.

Conclusions: An MCT supplement can provide energy to hepatocytes and promote hepatic lipogenesis, leading to a reduction in the cytosolic NADH/NAD+ ratio. MCT supplementation under a low-carbohydrate formula could be a promising therapy for CTLN2 and should also be used to prevent CTLN2 to avoid irreversible liver damage.

No MeSH data available.