Kidney Week

Abstract: SA-PO589

Cobalamin C Deficiency Induces a Specific Histopathological Pattern Associating Renal Thrombotic Microangiopathy and Characteristic Glomerular Lesions

Session Information

• Noncystic Mendelian Diseases
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 802 Non-Cystic Mendelian Diseases

Authors

• Guerrot, Dominique, Rouen University Hospital, Rouen, France

Dominique Guerrot,

• Lemoine, Mathilde, Rouen University Hospital, Rouen, France

Mathilde Lemoine,

• Grange, Steven, Rouen University Hospital, Rouen, France

Steven Grange,

• Rabant, Marion, NECKER Hospital, PARIS, France

Marion Rabant,

• Chatelet Pouliquen, Valerie, Rouen University Hospital, Rouen, France

Valerie Chatelet Pouliquen,

• Cornec-Le Gall, Emilie, Mayo Clinic, Rochester, Alabama, United States

Emilie Cornec-Le Gall,

• AMBROSETTI, Damien, CHU Nice, Nice, France

Damien AMBROSETTI,

• Deschênes, Georges, Hospital Robert Debre, Paris, France

Georges Deschênes,

• Francois, Arnaud, Rouen University Hospital, Rouen, France

Arnaud Francois,

Background

CblC deficiency is the most common inborn error of vitamin B12 metabolism. CblC deficiency most frequently presents as failure to thrive, neurologic deterioration, and hematologic abnormalities during the first year of life. Renal failure attributed to thrombotic microangiopathy (TMA) has occasionally been described, in the rarer late-onset presentation of CblC deficiency, in children and young adults. Due to the rarity of the disease and of available kidney biopsies, kidney lesions associated with CblC deficiency remain poorly defined. This study aims to describe the characteristics of kidney disease in cblC deficiency, and to provide a comparative histological analysis with cblC-independent renal TMA.

Methods

We performed a multicenter retrospective study including 7 patients with cblC deficiency and available kidney biopsy, and 16 matched controls with cblC-independent TMA. The histological characteristics were established by a systematic centralized review.

Results

The patients included were aged 6 to 26 years at the time of the first manifestations. All patients presented with acute renal failure, proteinuria and hemolysis. Five required dialysis. The histological study revealed arteriolar and glomerular TMA in all patients. After comparison with the cblC-independent TMA control group, a vacuolated aspect of the glomerular basement membrane (GBM) (86% vs 7% cases, p<0.001) and the intensity of glomerular parietal IgM deposits (score 1.8±0.8 vs 0.4±0.5, p<0.01) were more present in cblC deficiency patients than in controls. Six patients were treated by hydroxycobalamin. All of them improved with disappearance of hemolysis and 3 of the 4 patients requiring renal replacement therapy were weaned off dialysis.

Conclusion

This study provides the first demonstration of characteristic kidney pathology in CblC deficiency, combining lesions of glomerular and arteriolar TMA, a vacuolated aspect of the GBM and glomerular IgM deposits. Due to major therapeutical implications, we suggest patients with renal TMA be screened for CblC deficiency regardless of age, particularly when the kidney biopsy shows a vacuolated aspect of the GBM and glomerular parietal IgM deposition.