Serum amino acids in patients with mutations in the hepatocyte nuclear factor-1 alpha gene

Aims: Knockout mice lacking both copies of the hepatocyte nuclear factor 1 (HNF1) gene have altered serum levels of amino acids and generalized amino-aciduria. The aim of our study was to test whether alterations in serum amino acid levels were found in patients with mutations in the hepatocyte nuclear factor-1 alpha (HNF-1α) gene compared with controls.

Methods: Fasting serum from 20 patients with HNF-1α mutations and 20 age, sex and body mass index-matched controls was analysed for 16 amino acids. Means were compared between the two groups and Z scores calculated.

Results: There was no significant difference between patients with HNF-1α mutations and controls in serum levels of phenylalanine, arginine, citrulline or lysine as suggested by knockout mice models. Although serum levels of eight amino acids were different in the two groups, these were not significant after Bonferroni correction.

Conclusions: The alterations in serum amino acid levels seen in mice models are not seen in patients with mutations in the HNF-1α gene. This suggests differences in mouse and man in the regulation of amino acid transport and has not provided us with a phenotypic marker to use before confirmatory genetic testing.