PREVENTION

Based on the current research on citrin deficiency, the following factors may prevent the onset and/or worsening of symptoms associated with FTTDCD or CTLN2:  

High protein and fat, low carbohydrate diet 

Patients should adhere to a diet that is rich in protein and fat, while being low in carbohydrates to prevent hyperammonemia and failure to thrive in growing children [Okano et al. 2019, Saheki et al. 2020, Häberle & Rubio 2022]. 

MCT supplementation 

MCT is rapidly absorbed by liver cells as medium-chain fatty acids and metabolized to acetyl-CoA, which is then oxidized in the tricarboxylic acid (TCA) cycle to produce energy in the form of adenosine triphosphate (ATP). MCT supplementation also promotes de novo lipogenesis, reducing redox stress via the malate-citrate shuttle by converting excess cytosolic NADH to NAD+ [Hayasaka 2021; Hayasaka 2023]. Therefore, MCT supplementation may improve the metabolic disturbances resulting from a dysfunctional malate-aspartate shuttle. Based on the biochemical benefits of MCT supplementation, it may be advisable for patients to continue taking MCT even after the improvement of their clinical symptoms [Kido et al. 2022; Hayasaka 2023]. 

PRECAUTIONS

Things to avoid for citrin deficiency patients

High Carbohydrate Diet

While a low protein/high carbohydrate diet may be recommended for other classical urea cycle enzyme deficiencies to prevent hyperammonemia, this can be harmful for individuals with citrin deficiency. A diet high in carbohydrates will increase cytosolic NADH, thus worsening redox stress and can lead to metabolic derangements such as hyperammonemia, hypertriglyceridemia, and fatty liver [Saheki et al. 2020].

Infusion of sugars, such as glycerol, fructose and glucose

CTLN2 patients who have developed brain edema and were treated with glycerol-containing osmotic agents have shown rapid deterioration and may sometimes be fatal. Therefore, the use of glycerol or high fructose containing infusions are contraindicated in citrin deficiency patients. The reason for this is because the metabolism of glycerol or fructose generates NADH in the cytosol, which further worsens the redox state in patients [Yazaki et al. 2005, Saheki et al. 2020]. Infusions with high glucose solutions have also been reported to further deteriorate patient symptoms [Tamakawa et al. 1994]. Note that mannitol infusions appear to be well-tolerated and safe for citrin deficiency patients [Yazaki et al. 2005].

Alcohol

The metabolism of alcohol by the enzyme alcohol dehydrogenase (ADH) results in the generation of cytosolic NADH in the liver. Therefore, the consumption of alcohol can trigger the onset of CTLN2 and should be strictly avoided by patients [Saheki et al. 2020].

Medications

Early reports have shown that acetaminophen (or paracetamol) and rabeprazole may trigger CTLN2 [Siohama et al 1993, Imamura et al. 2003]. However, since these initial reports, there have not been further cases documented, which suggests that the effects of these drugs may be limited [Okano et al. 2019]. Care should be taken and symptoms monitored closely if these drugs need to be prescribed.

Please find the list of references here.

MONITORING AND TREATMENT
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