Abstract: TH-PO606

A Girl with a Mutation of the Ciliary Gene CC2D2A Presenting with FSGS and Nephronophthisis

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports


  • Matsumura, Kazuya, Keio University School of Medicine, Tokyo, Japan
  • Asada, Nariaki, Keio University School of Medicine, Tokyo, Japan
  • Hashiguchi, Akinori, Keio University School of Medicine, Tokyo, Japan
  • Kosaki, Kenjiro, Keio University School of Medicine, Tokyo, Japan
  • Awazu, Midori, Keio University School of Medicine, Tokyo, Japan

It has been reported that mutations in the ciliary gene TTC21B and NPHP4 cause familial FSGS. We report a girl with a mutation of the ciliary gene CC2D2A presenting with FSGS and nephronophthisis.


The patient is a 6-year-old girl with mental retardation, postaxial polydactyly, and ataxic breathing. She was diagnosed as having compound heterozygous CC2D2A missense mutation at age 5. In retrospect, azotemia at 1 year and proteinuria at 5 years were recorded but unnoticed at local hospitals. At age 6, she was referred to pediatric nephrology service. Height was 106 cm (-1.5 SD), weight 12.6 kg (-2.3 SD), and BP 116/53 mmHg (>95th percentile). She had pretibial pitting edema. Urinalysis showed protein 3+, blood 2+, granular cast +, protein to creatinine ratio (pro/Cr) 6.6 g/gCr, ß2 microglobulin 112 μg/l, NAG/Cr 33 U/gCr, and selectivity index 0.09. Blood test revealed Hb 13.2 g/dl, UN 23.2 mg/dl, Cr 0.56 mg/dl (eGFR 66 ml/min/1.73 m2), cystatin C 1.34 mg/l, total protein 5.3 g/dl, albumin 2.4 g/dl, cholesterol 317 mg/dl, and uric acid 7.5 mg/dl. Serologic tests for glomerulonephritis were negative. Ultrasonography showed normal-sized kidneys with a cyst in the right. Losartan was started for hypertension and proteinuria. Open renal biopsy was performed. On light microscopy, 8 out of 24 glomeruli were globally sclerosed, and 3 showed segmental sclerosis or hyalinosis. Mild tubular dilatation, tubular atrophy, and interstitial fibrosis were observed. No immune deposits were seen. On electron microscopy, glomeruli showed foot process effacement with no electron dense deposits. Since losartan did not exert an obvious effect, treatment with prednisolone was tried. Urine pro/Cr decreased to 3.7 g/gCr, but prednisolone was discontinued after 10 days because she developed duodenal ulcer perforation that necessitated omentoplasty. CT scan performed then showed bilateral multiple cysts in the kidney. Since then she had been treated with losartan and dipyridamole. Her renal function rapidly deteriorated. Current serum creatinine is 2.6 mg/dl with urine pro/Cr 13 g/gCr.


Based on the clinically overt nephrotic syndrome and foot process effacement, FSGS in this patient was thought to be due to podocytopathy associated with CC2D2A mutation, rather than subsequent to chronic injuries secondary to nephronophthisis.