Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: Strategy to prevent CTLN2

Okano, Yoshiyuki; Ohura, Toshihiro; Sakamoto, Osamu; Inui, Ayano

doi:10.1016/j.ymgme.2019.06.004

Cited by 50 publications

(100 citation statements)

References 62 publications

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“…Current treatment strategies for FTTDCD include diet therapy (low carbohydrate and high protein and fat) and supplements (e.g., administration of sodium pyruvate and/or MCT) (25). A case reported by Otsuka et al (26) showed MCT therapy can prevent the onset of hypoglycemia during the so-called apparently healthy period.…”

Section: Discussionmentioning

confidence: 99%

A Case Report: Can Citrin Deficiency Lead to Hepatocellular Carcinoma in Children?

Zhang

et al. 2019

Front. Pediatr.

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Citrin deficiency initially presents as neonatal intrahepatic cholestasis (NICCD) and often resolves within first year of infancy. Failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) has been recently proposed as a novel post-NICCD phenotype and its clinical features are still being established. Herein, we encountered a 2-year-old girl who was hospitalized for intermittent fever lasting 10 days. Besides pneumonia, we observed an NICCD-like phenotype with the presence of liver dysfunction, dyslipidemia, aminoacidemia, organic academia, and extremely high levels of alpha-fetoprotein (AFP). Genetic testing confirmed the diagnosis of citrin deficiency and, liver histology revealed she had already developed cirrhosis. Although, improvement of biochemical parameters and liver histology were observed after treatment that included dietary restrictions and symptomatic treatments, AFP levels remained elevated (>400 ng/ml) during a 3-year follow-up period. Moreover, liver magnetic resonance imaging (MRI) examination performed on the patient at age 5 revealed the development of multiple liver nodules with diffusion restriction on diffusion-weighted imaging (DWI). These observations highly indicate the possibility of hepatocellular carcinoma (HCC). Thus, this case reveals that an NICCD-like phenotype complicated with cirrhosis can exist during FTTDCD stage without any prior signs. It also emphasizes the necessity of monitoring AFP levels during follow-up for citrin deficiency patients with persistently high AFP level after treatment as FTTDCD may progress to HCC. Individualized treatment strategy for patients with FTTDCD also need to be explored.

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Section: Discussionmentioning

confidence: 99%

A Case Report: Can Citrin Deficiency Lead to Hepatocellular Carcinoma in Children?

Zhang

et al. 2019

Front. Pediatr.

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“…MCT: MCT was originally used as an energy supply for various metabolic diseases including NICCD [80]. Hayasaka et al [81] successfully used MCT for the treatment of CTLN2.…”

Section: Drugs or Supplements Used As Therapeutics For Citrin Deficiementioning

confidence: 99%

AGC2 (Citrin) Deficiency—From Recognition of the Disease till Construction of Therapeutic Procedures

et al. 2020

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Can you imagine a disease in which intake of an excess amount of sugars or carbohydrates causes hyperammonemia? It is hard to imagine the intake causing hyperammonemia. AGC2 or citrin deficiency shows their symptoms following sugar/carbohydrates intake excess and this disease is now known as a pan-ethnic disease. AGC2 (aspartate glutamate carrier 2) or citrin is a mitochondrial transporter which transports aspartate (Asp) from mitochondria to cytosol in exchange with glutamate (Glu) and H+. Asp is originally supplied from mitochondria to cytosol where it is necessary for synthesis of proteins, nucleotides, and urea. In cytosol, Asp can be synthesized from oxaloacetate and Glu by cytosolic Asp aminotransferase, but oxaloacetate formation is limited by the amount of NAD+. This means an increase in NADH causes suppression of Asp formation in the cytosol. Metabolism of carbohydrates and other substances which produce cytosolic NADH such as alcohol and glycerol suppress oxaloacetate formation. It is forced under citrin deficiency since citrin is a member of malate/Asp shuttle. In this review, we will describe history of identification of the SLC25A13 gene as the causative gene for adult-onset type II citrullinemia (CTLN2), a type of citrin deficiency, pathophysiology of citrin deficiency together with animal models and possible treatments for citrin deficiency newly developing.

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“…Sodium pyruvate may improve growth. The outcome of NICCD is generally good, with little intervention required by 12 months of age [174].…”

Section: Agc2 Deficiency (Omim #605814 #603471)mentioning

confidence: 99%

Amino Acid Transport Defects in Human Inherited Metabolic Disorders

Yahyaoui

Pérez‐Frías

2019

IJMS

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Amino acid transporters play very important roles in nutrient uptake, neurotransmitter recycling, protein synthesis, gene expression, cell redox balance, cell signaling, and regulation of cell volume. With regard to transporters that are closely connected to metabolism, amino acid transporter-associated diseases are linked to metabolic disorders, particularly when they involve different organs, cell types, or cell compartments. To date, 65 different human solute carrier (SLC) families and more than 400 transporter genes have been identified, including 11 that are known to include amino acid transporters. This review intends to summarize and update all the conditions in which a strong association has been found between an amino acid transporter and an inherited metabolic disorder. Many of these inherited disorders have been identified in recent years. In this work, the physiological functions of amino acid transporters will be described by the inherited diseases that arise from transporter impairment. The pathogenesis, clinical phenotype, laboratory findings, diagnosis, genetics, and treatment of these disorders are also briefly described. Appropriate clinical and diagnostic characterization of the underlying molecular defect may give patients the opportunity to avail themselves of appropriate therapeutic options in the future.

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Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: Strategy to prevent CTLN2

Cited by 50 publications

References 62 publications

A Case Report: Can Citrin Deficiency Lead to Hepatocellular Carcinoma in Children?

A Case Report: Can Citrin Deficiency Lead to Hepatocellular Carcinoma in Children?

AGC2 (Citrin) Deficiency—From Recognition of the Disease till Construction of Therapeutic Procedures

Amino Acid Transport Defects in Human Inherited Metabolic Disorders

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