The Case | A patient with autosomal dominant polycystic kidney disease with an atypical kidney magnetic resonance image

A 30-year-old woman attended our clinic to confirm the diagnosis of autosomal dominant polycystic kidney disease (ADPKD). An abdominal ultrasound performed at the age of 18 years showed multiple hepatic and bilateral kidney cysts. Relevant family history included a clinical diagnosis of ADPKD in her father, who received a kidney transplant at the age of 53 years, and in her brother. Moreover, a family history of cardiovascular disease was reported on both paternal and maternal sides of the family. On review of symptoms, the patient reported recurrent episodes of abdominal pain, headache, impaired sweating, and numbness and tingling in her extremities. Her blood pressure, kidney function, and laboratory examination findings were normal, with the exception of mild proteinuria (0.3 g/24 h). Abdominal magnetic resonance imaging showed multiple hepatic and bilateral kidney cysts, and in addition showed multiple bilateral parapelvic cysts, leading to stretching and compression of the calyces in coronal (Figure 1a) and axial (Figure 1b) T2-weighted magnetic resonance images. What is your diagnosis? On these bases, the patient underwent testing of a next-generation sequencing panel of 63 genes associated with cystic kidney disorders currently used in our clinic. The results showed the presence of the variant c.10549G>T in the PKD1 gene, with the coexistence of the variant c.868A>C in the GLA gene. Mutations in the GLA gene cause Fabry disease (FD), a rare X-linked lysosomal storage disorder, leading to a multisystemic disease. Because renal parapelvic cysts were reported in a large proportion of patients with FD, the GLA gene was included in our next-generation sequencing panel used to explore the genetic basis of the heterogeneous spectrum of renal cystic disorders. The patient’s family members were screened for both ADPKD and FD: the PKD1 variant was found in her father and brother, whereas the GLA variant was found in her mother and brother. The presence of parapelvic cysts in FD has been widely reported in the literature, and it is not clear if they could be related to the defect of glycosphingolipid metabolism1Capuano I. Buonanno P. Riccio E. et al.Parapelvic cysts: an imaging marker of kidney disease potentially leading to the diagnosis of treatable rare genetic disorders? a narrative review of the literature.J Nephrol. 2022; 35: 2035-2046Crossref Scopus (3) Google Scholar; in particular, the first data reported a prevalence of 50% of parapelvic cysts in patients with FD, detected by computed tomography or magnetic resonance imaging. A recent national, multicenter study demonstrated that the prevalence of parapelvic cysts, observed during a routine ultrasonography study, was significantly higher in patients with FD (28.9%) compared with control subjects of similar age and level of renal function (1.1%), and that such prevalence became even higher (43%) when the specific ultrasonography was performed.2Pisani A. Petruzzelli Annicchiarico L. et al.Parapelvic cysts, a distinguishing feature of renal Fabry disease.Nephrol Dial Transplant. 2018; 33: 318-323Crossref Scopus (22) Google Scholar More recently, Azambuja Neves et al. also highlighted the more frequent occurrence of parapelvic cysts in patients with FD compared with those with different glomerulopathies, regardless of the age, gender, and stage of chronic kidney disease.3Azambuja Neves R.F.C. Varela P. Fernandes D.E. et al.Renal ultrasound contributes to Fabry disease diagnosis.J Rare Dis Res Treat. 2020; 5: 19-23Crossref Google Scholar Although, to date, parapelvic cysts cannot be considered a pathognomonic sign of FD, their presence should alert both nephrologists and radiologists to consider the diagnosis of FD, especially in subjects with an unclear family history of renal disease and when other stigmata of the disease are evident. Our patient, although with the diagnosis of ADPKD, reported symptoms uncommon for polycystic disease; therefore, this finding, together with the evidence of parapelvic cysts at magnetic resonance imaging, raised suspicion for another coexisting cystic disease. In most cases of ADPKD, genetic testing is not required. However, although ADPKD diagnosis is often straightforward, misdiagnosis is possible when presumptive family history is not associated with genetic confirmation, because other heritable multifocal cystic diseases can present without their distinguishing manifestations. Hence, both clinical and radiological features should guide proper diagnosis in heritable multifocal cystic diseases, and the presence of atypical features should always increase the suspicion. Molecular genetic analysis should be performed in all suspected cases, with the aim to confirm the diagnosis and to address the specific available therapy.