Citrin Deficiency: Clinical and Nutritional Features

Abstract

SLC25A13 gene mutations are responsible for diseases related to citrin deficiency (CD), such as neonatal intrahepatic cholestasis caused by citrin deficiency and adult-onset type II citrullinemia (CTLN2). From childhood to adulthood, CD patients are apparently healthy due to metabolic compensation with peculiar dietary habits—disliking high-carbohydrate foods and liking fat and protein-rich foods. Carbohydrate overload and alcohol consumption may trigger the sudden onset of CTLN2, inducing hyperammonemia and consciousness disturbance. Well-compensated asymptomatic CD patients are sometimes diagnosed as having non-obese (lean) non-alcoholic fatty liver disease and steatohepatitis, which have the risk of developing into liver cirrhosis and hepatocellular carcinoma. CD-induced fatty liver demonstrates significant suppression of peroxisome proliferator-activated receptor α and its downstream enzymes/proteins involved in fatty acid transport and oxidation and triglyceride secretion as a very low-density lipoprotein. Nutritional therapy is an essential and important treatment of CD, and medium-chain triglycerides oil and sodium pyruvate are useful for preventing hyperammonemia. We need to avoid the use of glycerol for treating brain edema by hyperammonemia. This review summarizes the clinical and nutritional features of CD-associated fatty liver disease and promising nutritional interventions.

Nutritional support therapy for liver transplantation in an adult-onset type II citrullinemia patient: a case report

“…CTLN2 shows clinical manifestations with hyperammonemia and citrullinemia, and repeatedly impaired consciousness. It is reported that the prognosis of CTLN2 patients exhibiting hyperammonemia and serious encephalopathy is poor ( 9 ). A review of CTLN2 revealed that while conservative therapies, such as arginine and sodium pyruvate administration, high doses of glycerol and fructose infusion for brain edema, hyperalimentation, a low-protein and high-carbohydrate diet, have provided temporary relief from hyperammonemia, they have not improved the long-term prognosis ( 3 ).…”

“…The nutritional recommendations based on the current guidelines were not found to be applicable for practical management of our patient, we had to formulate a more individualized nutritional treatment plan based on the patient's pathophysiological characteristics and thorough review of relevant literature.In light of this, extensive literature review revealed that medium-chain triglycerides (MCT) have shown promise in ameliorating the symptoms of patients with CD. The use of MCT and lactose-restricted formula has been identified as an effective therapy for intrahepatic cholestasis in NICCD ( 9 ). Meanwhile, a low-protein, high-sugar diet, a common treatment for hepatic encephalopathy, exacerbates hyperammonemia in CTLN2.…”

“…At the same time, CTLN2 patients exhibit a dietary preference to a high-fat diet and distaste for carbohydrates due to their unique metabolic patterns. Nutritionists or nutritional pharmacists need to maintain their dietary habits rich in fat and protein to offset their abnormal metabolism ( 9 ).…”

“…We also advised dietary interventions to maintain the appropriate protein-fat-carbohydrate ratio. For instance, a recommended ratio of 15-25% protein, 40-50% fat, and 30-40% carbohydrate was suggested ( 9 ). Additionally, the patient was required to take long-term immunosuppressants like tacrolimus after surgery to combat immune rejection.…”