Beyond the Liver: Alagille Syndrome’s SilentImpact on Chronic Kidney Disease
DOI:
https://doi.org/10.71749/pkj.133Keywords:
Alagille Syndrome, Jagged‑1 Protein, Kidney Failure, Chronic, Receptor, Notch2, Renal Replacement TherapyAbstract
Alagille syndrome (AS) is a multisystemic autosomal dominant disorder caused by mutations in JAG1 or NOTCH2, with variable manifestations affecting the liver, heart, skeleton, eyes, kidneys, and other organs. While hepatic and cardiac features are classically emphasized, renal involvement is increasingly recognized but often underdiagnosed, particularly in adults with chronic kidney disease (CKD) of unknown etiology. We report the case of a 33-year-old Caucasian man who presented with stage 5 CKD of unknown origin and was on maintenance hemodialysis. His medical history included a childhood liver biopsy revealing bile duct paucity and abnormal liver enzymes. However, no definitive diagnosis had been previously established. The diagnosis of AS was only considered after his daughter was diagnosed with tetralogy of Fallot, prompting genetic screening. A heterozygous pathogenic variant in JAG1 c.2230C>T p.(Arg744*) confirmed the diagnosis of AS. This case highlights the diagnostic challenges of AS in adult patients presenting with renal insufficiency as the predominant feature. Despite a syndromic phenotype and early liver abnormalities, the absence of a unifying diagnosis delayed recognition. Renal involvement in AS is diverse and may include renal dysplasia, tubular dysfunction, and vascular anomalies such as renal artery stenosis. A growing body of evidence supports the utility of genetic testing in unexplained CKD, particularly in syndromic young adults. In this case, a definitive diagnosis enabled genetic counseling and avoided further unnecessary investigations.
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Data Availability Statement
The data supporting the findings of this case report are available from the corresponding author upon reasonable request.
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Copyright (c) 2026 Bernardo Fernandes, Pedro Lisboa-Gonçalves, Isabel Tavares, João Paulo Oliveira
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