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An undescribed subset of neonatal intrahepatic cholestasis associated with multiple hyperaminoacidemia
1Department of Pediatrics, Tohoku University School of Medicine, Aoba-ku, Seiryo-machi 1-1, 980-8574, Sendai, Japan
Insights
Neonatal screening identified five infants with cholestatic jaundice and hyperaminoacidemia. Treatment with vitamins and medium-chain triglyceride formula normalized amino acid profiles and liver function.
Area of Science:
- Biochemistry
- Pediatrics
- Neonatology
Background:
- Neonatal mass screening programs aim to detect metabolic disorders early.
- Cholestatic jaundice and hyperaminoacidemia can indicate underlying metabolic conditions in newborns.
- Homocystinuria screening sometimes reveals other unexpected metabolic derangements.
Purpose of the Study:
- To report the identification and clinical course of five neonates with unexplained cholestatic jaundice and multiple hyperaminoacidemias.
- To characterize the specific amino acid abnormalities and liver pathology in affected infants.
- To evaluate the efficacy of therapeutic intervention.
Main Methods:
- Neonatal mass screening for homocystinuria.
- Analysis of plasma amino acid profiles.
- Liver biopsy for histopathological examination.
- Clinical monitoring of liver function tests and amino acid levels during treatment.
Main Results:
- Five patients presented with cholestatic jaundice and elevated plasma levels of methionine, citrulline, tyrosine, threonine, phenylalanine, lysine, and arginine.
- Significantly higher levels of citrulline, methionine, and threonine were observed compared to controls with idiopathic neonatal hepatitis and biliary atresia.
- Liver biopsies revealed diffuse hepatic steatosis without giant cell transformation.
- Treatment with fat-soluble vitamins and medium-chain triglyceride formula normalized amino acid profiles within 6 weeks.
- All liver function tests normalized by 17 months of age.
Conclusions:
- The study identified a distinct group of neonates with cholestatic jaundice and a specific pattern of hyperaminoacidemia.
- Hepatic steatosis is a key histopathological finding in these patients.
- Early diagnosis and targeted nutritional therapy, including medium-chain triglycerides, are effective in managing this condition.
- This highlights the importance of comprehensive metabolic evaluation in neonates with unexplained cholestasis.
Abstract:
Five patients of cholestatic jaundice and multiple hyperaminoacidemias were uncovered during neonatal mass screening for homocystinuria. All five patients had increased plasma levels of methionine, citrulline, tyrosine, threonine, phenylalanine, lysine and arginine. Compared with those of age-matched cholestatic disease controls, idiopathic neonatal hepatitis (n=9) and biliary atresia (n=14), plasma levels of three amino acids, citrulline, methionine, and threonine, were significantly greater, respectively (P<0.01). Liver biopsies examined in four patients uniformly showed diffuse hepatic fatty liver with micro- and macrovesicular droplets without giant cell transformation. Administration of fat-soluble vitamins and formula milk containing middle-chain triglyceride resulted in normalization of amino acid profiles by 6 weeks after the treatment. All liver function tests normalized by 17 months of age.