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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 4  |  Page : 840-843
Caroli's syndrome with autosomal recessive polycystic kidney disease

Division of Pediatric Nephrology, Department of Pediatrics, Lokmanya Tilak Municipal General Hospital and Medical College, Sion, Mumbai, India

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Date of Web Publication24-Jun-2014


Caroli's syndrome (CS) is a rare congenital disorder characterized by multiple segmental cystic or saccular dilatations of the intrahepatic bile ducts and congenital hepatic fibrosis. We report a 9-year-old boy who was diagnosed with CS and autosomal recessive poly-cystic kidney disease. On screening, his 5-month-old asymptomatic sister had multiple dilated biliary radicals with multiple bilateral renal cystic lesions. Both the patient and the affected sibling have been advised regular follow-up for monitoring the progression of the disease. In conclusion, patients with CS should be screened for renal cystic lesions and vice versa even if they are asymptomatic. Also, as the disease is inherited in an autosomal recessive manner, it is important to screen family members for early diagnosis and management.

How to cite this article:
Shenoy P, Zaki SA, Shanbag P, Bhongade S. Caroli's syndrome with autosomal recessive polycystic kidney disease. Saudi J Kidney Dis Transpl 2014;25:840-3

How to cite this URL:
Shenoy P, Zaki SA, Shanbag P, Bhongade S. Caroli's syndrome with autosomal recessive polycystic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2022 Nov 28];25:840-3. Available from: https://www.sjkdt.org/text.asp?2014/25/4/840/135176

   Introduction Top

Caroli's disease (CD), first described in 1958 by Jacques Caroli, is a rare inherited disorder charac-terized by multiple segmental cystic or saccular dilatations of the intrahepatic bile ducts. [1] The disease is referred as "Caroli's syndrome" (CS) when it is associated with congenital hepatic fibrosis (CHF). [1],[2] The pre­valence of CS is approximately one in 6,000- 40,000 newborns. [2] Owing to the rarity of this disorder, the diagnosis and treatment is often delayed. Autosomal recessive polycystic kidney disease (ARPKD) has an estimated incidence of one in 20,000 live births, and is frequently associated with CS. [3] We herein present a child who was diagnosed to have CS with conco­mitant ARPKD.

   Case Report Top

A 9-year-old boy, born of a third-degree con-saguineous marriage, presented with progres­sively increasing lower limb deformity for four years [Figure 1]. There was no history of urinary complaints, jaundice, ataxia, visual complaints, abdominal distension or bleeding manifestations. His family history was unre­markable. On examination, he was hemodyna-mically stable with a blood pressure of 96/50 mm Hg. His height was 105 cm and weight was 17 kg (<3 rd percentile for age). Pallor was present, but there was no icterus, edema or clubbing. His liver was non-tender, firm with sharp margins and a span of 12 cm. His spleen was palpable 5 cm below the left costal margin and the left kidney was ballotable.
Figure 1: Clinical photograph of the patient showing genu valgum.

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Laboratory investigations revealed hemoglo­bin 8.4 g/dL, total bilirubin 0.8 mg/dL, serum alanine transaminase 11 IU/L, total protein 7.6 g/dL and serum albumin 3.4 g/dL, blood urea nitrogen 15 mg/dL and serum creatinine 1.2 mg/dL. The estimated glomerular filtration rate was 48.13 mL/1.73 m [2] /min by the Schwartz formula. [4] Alkaline phosphatase was 1127 IU, serum calcium was 8 mg/dL and inorganic phosphorus was 2.6 mg/dL. The serum para-thormone level was 287 pg/mL (N 12-72 pg/ mL). The 25-hydroxy-vitamin D level was 20.6 ng/mL, suggesting insufficiency. Arterial blood gas analysis showed pH 7.29, bicarbonate level 14 meq/L and pCO 2 28 mm Hg.

Ultrasound of the abdomen showed altered echogenicity of the liver with a coarse, non-homogeneous pattern, splenomegaly and mul­tiple intrahepatic dilated biliary radicals with central hyperechoic areas predominantly in the right lobe of the liver. Both kidneys were enlarged and showed increased echogenicity with loss of normal corticomedullary differen­tiation and multiple cystic lesions. These fin­dings were confirmed with a contrast-enhanced computerized tomography of the abdomen [Figure 2] and [Figure 3]. Porto-splenic venous Doppler was suggestive of portal venous hypertension. Upper gastrointestinal endoscopy revealed grade II gastric varices. A final diagnosis of CS with portal hypertension and autosomal recessive polycystic kidney disease was made. As the diagnosis was confirmed on imaging, liver biopsy was not performed.
Figure 2: Computerized tomography scan of the abdomen showing bilateral bulky kidneys with loss of normal cortico-medullary differentiation and scattered medullary cysts.

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Figure 3: Computerized tomography scans of the abdomen showing multiple areas of focal intrahepatic biliary radicals dilatation. Also seen is the narrowed caliber of main portal vein with multiple dilated collaterals. Tiny dots, representing intraluminal portal veins, within the dilated intrahepatic bile ducts are seen (central dot sign).

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The child was started on ursodeoxycholic acid, oral sodium bicarbonate and 25-hydroxy-vitamin D supplements (50,000 IU/month). The family members of the patient were screened. His parents and elder sister had a normal abdominal ultrasound. However, his 5-month-old asymptomatic sister had multiple dilated biliary radicals with bilateral renal multiple cystic lesion, but her renal and liver function tests were normal. Both the patient and the affected sister have been advised regular follow-up for monitoring the progression of the disease.

   Discussion Top

CS is a subset of the "hepatorenal fibrocystic disease" (HRFD) family. HRFDs are inherited disorders that belong to a larger group of disorders collectively referred to as "cilio-pathies." [5] The ductal plate malformation (DPM), a developmental abnormality of the porto-biliary system, is the basis of the liver disease in CS. The severity of DPM and the level of the affected portobiliary tree results in a spec­trum of abnormalities including congenital hepatic fibrosis (CHF) (microscopic bile ducts), CS (microscopic and medium size bile ducts) and CD (medium and large bile). [1],[2],[5] Many authors believe that CD and CS are actually different stages of the same disease charac­terized by peri-portal fibrosis and ductal dila-tation. [6] The liver cysts in CS are non-obstruc­tive dilatations of the intrahepatic biliary tree and are continuous with the biliary system. CS usually becomes symptomatic in childhood and young adults, but may also go unrecog-nized. [1],[6] The clinical course ranges from recur­rent cholangitis without complications to pro­liferation of dilated small terminal intra-hepatic canaliculi with cirrhosis and portal hypertension, formation of intracystic stones, hepatic abscesses, secondary amyloidosis or pancreatitis and cholangiocarcinoma. [1],[2],[6],[7] As hepatic fibrosis in CS is dynamic and pro­gressive, portal hypertension is usually a late feature. Also, hepatocellular function of the liver is relatively well preserved in the early stages, with liver enzymes being either normal or mildly elevated. [5],[6] Thrombocytopenia and leukopenia are present with portal hyperten­sion and hypersplenism. The elevated erythro-cyte sedimentation rate and leukocytosis may indicate cholangitis. Renal function tests can be deranged in CS having associated renal involvement, as in our patient. [6] Our patient presented with stage III chronic kidney disease with acidosis and rickets.

Definitive diagnosis of CS is confirmed with imaging studies such as ultrasonography, endoscopic/magnetic retrograde cholangiopan-creaticography, computed tomography (central dot sign), radionuclide hepatobiliary imaging, intraoperative cholangiography and percuta­neous transhepatic cholangiography. [1],[5],[6],[7] Ultra-sonography reveals increased echogenicity of the liver with a coarse, non-homogeneous pat­tern, splenic enlargement as an evidence for PH and macroscopic liver cysts. These fin­dings, especially in the context of fibrocystic renal involvement, are diagnostic of CS and hence liver biopsy is not required in all cases. [5] As CS is a member of the HRFD family, involvement of the kidney should be assessed. Liver involvement in HRFD includes CHF, biliary hamartomas, autosomal dominant poly-cystic disease and CD and choledochal cysts. [8] Associated cystic dilatation of the kidneys is seen in 60-80% of the cases of CS, which may include renal tubular ectasia, medullary sponge kidney, cortical cyst, ARPKD or, rarely, auto-somal dominant polycystic kidney disease. [1],[6],[7] The association of Caroli's disease with ARPKD has been well described. [2],[9],[10],[11] Waters et al in a study of 15 children with ARPKD found that 60% of them had associated asymptomatic CD of the liver. [9] Also, Pinto et al in a study of ten cases of CD found that 80% of them had associated ARPKD. [10] However, Dias et al in a study of 25 children with ARPKD found that only 20% of them had associated Caroli's syn­drome (CS). [11] The patients are usually asymp­tomatic (as far as renal disease is concerned), but may develop renal stone disease and infection. This associated form of CS is trans­mitted as an autosomal recessive pattern. The association between CHF and ARKPD is caused by mutations in the PKHD1 gene that encodes fibrocystin, a protein of primary cilia. [3],[6] ARPKD is characterized by renal cysts arising from dilated collecting ducts. [3] Our patient and his sibling met the modified clin­ical diagnostic criteria of ARPKD by Zerres et al. [12]

Medical treatment of CS includes antibiotics for cholangitis, ursodeoxycholic acid for cho-lestasis, beta blocker therapy and treatment of varices for portal hypertension. [1],[6],[13] Surgical treatment depends on the clinical features and the location of the biliary abnormalities. Seg-mental or lobar hepatic resection provides symptomatic relief and removes the risk of malignancy when the abnormalities are loca­lized. In case of diffuse involvement of liver, treatment options include conservative ma­nagement, endoscopic therapy (sphincterotomy for clearance of intra-hepatic stone), internal biliary bypass procedures and liver transplan-tation. [1],[5],[6],[7],[13] If concomitant renal failure ensues from the dysplastic kidneys, liver transplan­tation combined with renal transplantation might be warranted. [2] Genetic counseling and screening of family members is important as the disease has an autosomal recessive inhe­ritance.

   Acknowledgment Top

The authors would like to thank the Dean of the institution for permitting them to publish this manuscript.

   References Top

1.Bavikar R, Kulkarni R. Caroli's syndrome: A case report. Curr Pediatr Res 2011;15:59-60.  Back to cited text no. 1
2.Kim JT, Hur YJ, Park JM, Kim MJ, Park YN, Lee JS. Caroli's syndrome with autosomal recessive polycystic kidney disease in a two month old infant. Yonsei Med J 2006;47:131-4.  Back to cited text no. 2
3.Harris PC, Torres VE. Polycystic kidney disease. Annu Rev Med 2009;60:321-37.  Back to cited text no. 3
4.Schwartz GJ, Haycock GB Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976;58:259-63.  Back to cited text no. 4
5.Gunay-Aygun M. Liver and kidney disease in ciliopathies. Am J Med Genet C Semin Med Genet 2009;151C:296-306.  Back to cited text no. 5
6.Yonem O, Bayraktar Y. Clinical characteristics of Caroli's syndrome. World J Gastroenterol 2007;13:1934-7.  Back to cited text no. 6
7.Mrowka C, Adam G, Sieberth HG, Matern S. Caroli's syndrome associated with medullary sponge kidney and nephrocalcinosis. Nephrol Dial Transplant 1996;11:1142-5.  Back to cited text no. 7
8.Brancatelli G, Federle MP, Vilgrain V, Vullierme MP, Marin D, Lagalla R. Fibro-polycystic liver disease: CT and MR imaging findings. Radiographics 2005;25:659-70.  Back to cited text no. 8
9.Waters K, Howman‐Gibes R, Rossleigh M, Lam A, Ureu R, Knight J. Intrahepatic bile duct dilatation and cholestasis in autosomal recessive polycystic kidney disease. Demons­tration with hepatobiliary scintigraphy. Clin Nucl Med 1995;20:892-5.  Back to cited text no. 9
10.Pinto RB, Lima JP, da Silveira TR, Scholl JG, de Mello ED, Silva G. Caroli's disease: Report of 10 cases in children and adolescents in southern Brazil. J Pediatr Surg 1998;33:1531-5.  Back to cited text no. 10
11.Dias NF, Lanzarini V, Onuchic LF, Koch VH. Clinical aspects of autosomal recessive poly-cystic kidney disease. J Bras Nefrol 2010;32: 263-7.  Back to cited text no. 11
12.Zerres K, Mücher G, Becker J, et al. Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): molecular genetics, clinical experience, and fetal morphology. Am J Med Genet 1998;76:137-44.  Back to cited text no. 12
13.Karim AS. Caroli's disease. Indian Pediatr 2004;41:848-50  Back to cited text no. 13

Correspondence Address:
Prithi Shenoy
Division of Pediatric Nephrology, Department of Pediatrics, Lokmanya Tilak Municipal General Hospital and Medical College, Sion, Mumbai - 400 022
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.135176

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  [Figure 1], [Figure 2], [Figure 3]

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