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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 1.The open circles, triangles and squares represent the levels of blood ammonia before treatment, at 14 days after treatment, and at 65 days after treatment, respectively.
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f0020: Diurnal change in blood ammonia in Case 1.The open circles, triangles and squares represent the levels of blood ammonia before treatment, at 14 days after treatment, and at 65 days after treatment, respectively.

Mentions: The patient was treated with a supplement of 45 mL of Macton oil under a low-carbohydrate formula (2,371 cal a day; protein: fat: carbohydrate ratio 11: 50: 39). He improved in his general fatigue within a week and had no recurrent episode of encephalopathy. The levels of postprandial blood ammonia, plasma citrulline, Fischer ratio, ALT, γ-GTP and PSTI were steadily improved by the therapy (Supplementary Fig. 1, Supplementary Fig. 2, Fig. 1, Table 1). After 10 months of therapy, his body weight increased to 60 kg, and the amount of Macton oil was decreased to 30 mL/day. Then, the levels of plasma citrulline and the Fischer ratio mildly deteriorated, and these parameters recovered with an increase in Macton oil to 45 mL/day. The patient had mild citrullinemia, and sometimes had postprandial mild hyperammonemia with no apparent symptoms. No signs of fatty liver were observed on an abdominal ultrasonography after 41 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 1.The open circles, triangles and squares represent the levels of blood ammonia before treatment, at 14 days after treatment, and at 65 days after treatment, respectively.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0020: Diurnal change in blood ammonia in Case 1.The open circles, triangles and squares represent the levels of blood ammonia before treatment, at 14 days after treatment, and at 65 days after treatment, respectively.
Mentions: The patient was treated with a supplement of 45 mL of Macton oil under a low-carbohydrate formula (2,371 cal a day; protein: fat: carbohydrate ratio 11: 50: 39). He improved in his general fatigue within a week and had no recurrent episode of encephalopathy. The levels of postprandial blood ammonia, plasma citrulline, Fischer ratio, ALT, γ-GTP and PSTI were steadily improved by the therapy (Supplementary Fig. 1, Supplementary Fig. 2, Fig. 1, Table 1). After 10 months of therapy, his body weight increased to 60 kg, and the amount of Macton oil was decreased to 30 mL/day. Then, the levels of plasma citrulline and the Fischer ratio mildly deteriorated, and these parameters recovered with an increase in Macton oil to 45 mL/day. The patient had mild citrullinemia, and sometimes had postprandial mild hyperammonemia with no apparent symptoms. No signs of fatty liver were observed on an abdominal ultrasonography after 41 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.