Assessment of Liver Metabolic Alterations in Vivo in Patients With Citrin Deficiency and Healthy Subjects by Metabolic Labeling With Stable Isotopes
Citrin is an aspartate-glutamate transporter in the liver that facilitates the urea cycle pathway for ammonia detoxification via ureagenesis. It is also thought to be involved in liver energy metabolism as a component of the malate-aspartate shuttle. The clinical presentation in patients supports the hypothesis that liver glycolytic, gluconeogenic and lipogenic functions are compromised in citrin deficiency, but none of the key hepatic pathway fluxes have been measured in patients to date. This is the first study that will examine the liver metabolic fluxes in patients with citrin deficiency. Liver metabolic functions will be examined by metabolic flux assays and biochemical measurements after application of stable isotopes 2H2O and \[U-13C6\]-fructose. Urea cycle metabolites and their enrichment after application of a stable isotope tracer 15NH4Cl will be measured to examine the liver's ability to detoxify ammonia into urea.
• Subjects with citrin deficiency, confirmed by genetic analysis to carry pathogenic variant(s) in the SLC25A13 gene
• Age from 18 years to 65 years inclusive
• Male or female
• Written informed consent has been given
• Understands and is willing, able and likely to comply with study procedures and restrictions
• Age from 18 years to 65 years inclusive, and not more than five years younger or older than the specified paired participant from the AACD group
• Same sex as the specified paired participant from the AACD group
• Same ethnicity the specified paired participant from the AACD group
• Written informed consent has been given
• Understands and is willing, able and likely to comply with study procedures and restrictions