Unidade de Nefrologia, Área da Pediatria, Centro Hospitalar Universitário de Lisboa Central, E.P.E.
- 53th Annual Scientific Meeting of the European Society for Paediatric Nephrology, Amsterdão, 16/19/9/2022, Poster
- Pediatric Nephrology (2021) 36:3422.
Introduction: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common inherited disorders, caused by PKD1 and PKD2 gene mutations, resulting in non-functioning polycistin-1(PC1) and polycistin-2(PC2), respectively. Mutations in GANAB, which encodes glucosidase II subunit α(GIIα), have recently been described in a small percentage of cases of ADPKD and usually presents with mild kidney disease.
Material and methods: Clinical cases description.
Results: We describe two 17-year-old patients with GANAB mutations, corresponding to 3.4% of our ADPKD paediatric cohort. Patient 1 presented with macroscopic haematuria since he was one-year-old. His family history was positive for nephrolithiasis, and he was initially diagnosed with nephrolithiasis. Patient 2 presented with flank pain and intermittent micro and macroscopic haematuria after renal trauma. He also had congenital partial deficit of factor XI and a positive family history for nephrolithiasis. Further investigation revealed bilateral renal cortical cysts and hypocitraturia in both patients. No hepatic involvement or hypertension were reported and the estimated glomerular filtration rate was normal. Next-Generation Sequencing revealed GANAB heterozygous mutations in both patients: c.1452+1G>A in patient 1 and p.Arg834Ter (c.2500C>T) in patient 2.
Conclusions: Our patients presented with intermittent haematuria and hypocitraturia, not typically described in the literature. Further workup showed bilateral renal cysts with preserved renal function and no other organ involvement. Although most ADPKD paediatric patients are asymptomatic, a small proportion presents with early-onset disease during childhood. GANAB mutations have been recently implicated in 0.3% of ADPKD cases, typically with milder kidney involvement. The knowledge of the genetic spectrum of cystic kidney disease may prompt an earlier diagnosis.
Keywords: GANAB, Polycystic Kidney Disease