You may find all the publications that have been supported by the Foundation below. Please click on the respective titles to read the publication.
- Clinical Landscape of Citrin Deficiency: A Global Perspective on a Multifaceted Condition. Kido et al. JIMD, 2023
This paper comprehensively reviews the existing literature on the clinical landscape of citrin deficiency and provides an updated global overview of the condition, examining its genetic basis, diverse clinical presentations, newborn screening, diagnosis, and clinical research. Notably, it introduces a new nomenclature: Adolescent and Adult Citrin Deficiency (AACD), replacing the previous term, Citrullinemia Type 2 (CTLN2). Additionally, for the first time, the paper shares updated clinical insights on the citrin deficiency cohort in the UK, contributed by one of the co-authors, Dr. Saikat Santra.
This review is much needed as it fills a significant gap in the literature. We believe the paper will greatly enhance our clinical understanding of citrin deficiency and serve as a valuable resource for the medical and research communities. The authors also dedicated this work to Professor Takeyori Saheki, a pioneer in the description of citrin deficiency and beyond.
- Food Preferences of Patients with Citrin Deficiency. Okamoto et al. Nutrients, 2021.
The survey study was designed to understand the food preference of citrin deficiency patients and to elucidate the important criteria for their food selection. The patients and their family who served as controls were asked their preference for 435 food items on a scale of 1-4. Survey results showed that patients disliked more foods than controls. The foods they dislike are found to contain higher carbohydrate, lower fat, and lower protein. The study also revealed that carbohydrate, among the energy-producing nutrients, had the strongest influence on patients’ food preference, and female patients tended to have a stronger aversion towards high carbohydrate foods compared to male patients.
The survey concluded that from very early childhood patients start to prefer foods that compensate for the metabolism dissonance caused by citrin deficiency. Appropriate dietary treatment may prevent the onset of CTLN2 and helps improve the wellness of children by preventing hypoglycemia, reducing fatigue, and improving their quality of life. Citrin Foundation sponsored this study on patient’s food preferences, and we hope that it serves as a helpful guide for patients, family members, and medical professionals in understanding the food preferences and important criteria of food selection for citrin deficiency patients.
You may read a summary of this publication here.
- Analysis of daily energy, protein, fat, and carbohydrate intake in citrin-deficient patients: Towards prevention of adult-onset type II citrullinemia. Okano et al. Mol Genet Metab, 2021.
The paper shares survey results showing that citrin deficiency patients typically had an energy intake that was 115% of the standard Japanese diet. Survey results also illustrated that patients typically had a diet with higher protein, higher fat and lower carbohydrate ratios as compared to the previous reports, even though the amount of carbohydrates consumed remained the same. Female patients were also reportedly less inclined to consume carbohydrates as compared to male patients. Lastly, while patients were reported to have a higher caloric intake, they generally were not overweight. These results shows us that a diet intervention that is high-energy and low in carbohydrates could potentially help citrin-deficient patients attain normal growth and prevent the onset of CTLN2.
Since the discovery of citrin deficiency, there has not been a cure developed for this disease. However, Dr Okano has improved on the current therapeutic interventions of the condition by providing an updated evaluation of food and nutritional intake and offering new dietary recommendations that could help to prevent the onset of CTLN2.
A summary of this study can be found here.
- Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: Strategy to prevent CTLN2. Okano et al. Mol Genet Metab, 2019.
The paper shares that the reported prevalence of CTLN2 in Japan is 1/100,000. However, the carrier rate is approximately 1 in 65 or 1 in 42 from the analysis of citrin-deficient gene. The estimated incidence of CTLN2 (1 in 17,000 or 1 in 7100, reported in the above two studies, respectively) is largely different from that of actual CTLN2-onset patients. These figures suggest that only few patients with citrin deficiency develop CTLN2. The onset of CTLN2 is triggered by various factors including alcohol intake, excessive carbohydrate ingestion, and fatigue. In other words, environmental factors such as diet play a role in the progression of CTLN2, together with the deficiency of the citrin gene. Liver transplantation was thought to be the most suitable treatment for CTLN2. However, the recent studies have demonstrated the effectiveness of arginine, sodium pyruvate, and medium chain triglyceride (MCT) oil, in addition to the diet therapy, which suggests the comprehensive treatment is important to prevent the onset of CTLN2. Recently, it has been reported that ornithine plus aspartate significantly reduces blood ammonia in a mouse model of citrin deficiency and is expected to effect on citrin deficient patients.
More than 20 years have passed since the responsible gene of CTLN2 was identified, and a number of clinical reports and studies have been published. In this paper, Dr. Okano summarized the current treatment during NICCD and the adaptation and compensation stage to prevent the onset of CTLN2.
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