In recent years we have witnessed a conceptual revolution in medicine, in which genetic studies have become a tool with a high yield rate in the diagnostic process.1 These tests have been particularly used in cases with a family history and/or multiple symptoms, which lead to a suspected diagnosis and then genetic testing directed towards a possible disease. Next-generation sequencing (NGS) specifically allows the sequencing of all the exome regions of genes. Due to their length, they are filtered using Human Phenotype Ontology (HPO) terms, which standardise phenotypic abnormalities and help prioritise findings based on clinical practice.2 We present two case reports of patients who only had nonspecific hepatic signs (hypertransaminasaemia or fatty liver), in which the HPO-driven clinical exome genetic study made it possible to make the aetiological diagnosis and/or support the cause of the clinical context.

Case 1: 11-year-old patient with no relevant medical history in whom, during a study for abdominal pain, we detected persistent hypertransaminasaemia (AST 35 U/l and ALT 44 U/l, normal values < 35 U/l) and ultrasound data of severe steatosis.

In anthropometry, the body mass index (BMI) was at the 80th percentile (p80). Initially, hygiene and dietary measures were indicated, with improvement in anthropometry (BMI p70), but persistence of the abnormal liver echotexture and hypertransaminasaemia.

The clinical presentation of these two rare diseases with clinical-radiological liver symptoms as the initial, and so far the only, manifestation are not described in the literature.

In paediatrics, about 40% of chronic liver diseases have a genetic cause, but also in adult patients, where recent studies5 report that 25% of nonspecific liver disorders without diagnosis are due to monogenic mutations.

The implementation of NGS in conjunction with HPO targeting specific liver disorders will

In both cases presented, the patients' legal representatives signed informed consent for their publication.

We did not receive any funding for the preparation and publication of this article.

The authors declare that they have no conflicts of interest.

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