Clinical and Laboratory ObservationsPossible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy☆
Section snippets
Case 1
A 2-month-old boy was brought to a local hospital with a complaint of abdominal distension. He was found to have ascites caused by hypoproteinemia (total protein 3.7 g/dL and albumin 2.0 g/dL). Total (7.6 mg/dL) and direct (3.4 mg/dL) bilirubin concentrations were elevated. The alkaline phosphatase level was 991 IU/L, and the γ-glutamyl transpeptidase level was 130 IU/L. Prothrombin time was markedly prolonged (61 seconds). His serum ammonia concentration was slightly elevated (87 μg/dL) but
Case 2
A 2-month-old girl was evaluated for jaundice; the serum levels of total (11.1 mg/dL) and direct (3.6 mg/dL) bilirubin were elevated. Aspartate aminotransferase level was 86 IU/L; alanine aminotransferase level, 23 IU/L; γ- glutamyl transpeptidase level, 152 IU/L; alkaline phosphatase level, 1744 IU/L; and bile acid concentration, 320.1 μmol/L. Serum protein concentrations were decreased. The lowest values were as follows: total protein, 4.0 g/dL; albumin, 3.5 g/dL; fibrinogen, 68 mg/dL;
Discussion
In early infancy, both of these patients had a marked decrease in serum protein concentrations and a moderate elevation in total bilirubin concentration, neither of which is a common sign of CTLN2. They had characteristic liver histologic findings that might be compatible with CTLN2. Other metabolic diseases including Wilson’s disease, hemachromatosis, glycogen storage disease, and cytomegalovirus and Epstein-Barr virus infections were ruled out in both cases. Computed tomography scan or
References (8)
- et al.
Hereditary disorders of the urea cycle in man: biochemical and molecular approaches
Rev Physiol Biochem Pharmacol
(1987) - et al.
Urea cycle enzymes
- et al.
Type II citrullinemia (citrin deficiency): a mysterious disease caused by a defect of calcium-binding mitochondrial carrier protein
- et al.
Pancreatic secretory trypsin inhibitor as a diagnostic marker for adult-onset type II citrullinemia
Hepatology
(1997)
Cited by (89)
Analysis of daily energy, protein, fat, and carbohydrate intake in citrin-deficient patients: Towards prevention of adult-onset type II citrullinemia
2021, Molecular Genetics and MetabolismCurrent treatment for citrin deficiency during NICCD and adaptation/compensation stages: Strategy to prevent CTLN2
2019, Molecular Genetics and MetabolismOral aversion to dietary sugar, ethanol and glycerol correlates with alterations in specific hepatic metabolites in a mouse model of human citrin deficiency
2017, Molecular Genetics and MetabolismCitation Excerpt :Human citrin deficiency, also known as mitochondrial aspartate-glutamate carrier 2 (AGC2) deficiency, is one of the most well-characterized genetic disorders associated with a member of the large SLC25A family of mitochondrial transporter proteins [1,2]. Now an established disease entity [3], citrin deficiency is caused by mutations in SLC25A13 that result in at least two previously distinct clinical presentations: adult-onset type II citrullinemia (CTLN2) characterized by hyperammonemia [4], and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) that leads to multiple aminoacidemias, galactosemia, hypoproteinemia and jaundice [5–7]. Citrin deficiency may also lead to additional consequences throughout life including growth retardation and hypoglycemia in infancy, fatty liver, hypertriglyceridemia, pancreatitis, and hepatocellular carcinoma [8–18], while a third phenotype, abbreviated FTTDCD and defined as failure to thrive and dyslipidemia [19,20] in an otherwise healthy individual, has also been described.
Circulating tricarboxylic acid cycle metabolite levels in citrin-deficient children with metabolic adaptation, with and without sodium pyruvate treatment
2017, Molecular Genetics and MetabolismMechanism for increased hepatic glycerol synthesis in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mouse: Urine glycerol and glycerol 3-phosphate as potential diagnostic markers of human citrin deficiency
2015, Biochimica et Biophysica Acta - Molecular Basis of Disease
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Reprint requests: Takeshi Tomomasa, MD, Department of Pediatrics, Gunma University School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan.