ESPN 50th Annual Meeting

ESPN 2017


 
Response to rituximab of nephrotic syndrome in a child with IPEX syndrome
MAGDALENA DROZYNSKA-DUKLAS 1 ILONA ZAGOZDZON 1 MALGORZATA MYSLIWIEC 2 WOJCIECH MÅ‚YNARSKI 3 NINELA IRGA-JAWORSKA 4 ALEKSANDRA ZUROWSKA 1

1- DEPARTMENT OF PAEDIATRICS, NEPHROLOGY AND HYPERTENSION, MEDICAL UNIVERSITY OF GDANSK
2- DEPARTMENT OF PAEDIATRICS, DIABETOLOGY AND ENDOCRINOLOGY,MEDICAL UNIVERSITY OF GDANSK
3- DEPARTMENT OF PAEDIATRICS, ONCOLOGY, HAEMATOLOGY AND DIABETOLOGY, MEDICAL UNIVERSITY OF LODZ
4- DEPARTMENT OF PAEDIATRICS, HAEMATHOLOGY AND ONCOLOGY, MEDICAL UNIVERSITY OF GDANSK
 
Introduction:

 Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a rare genetically determined disorder, caused by a mutation of the gene encoding FOXP3. This  causes dysfunction of the regulatory T cells leading to a variety of autoimmunological disorders including :diabetes mellitus,  autoimmune enteropathy and hypothyroidism. Among 160 published cases  only 12 demonstrated glomerular involvement. Treatment involves bone marrow transplantation (BMT). The report presents a subject with IPEX syndrome who manifested with steroid resistant nephrotic syndrome

Material and methods:

 A 12 months old child with neonatal diabetes mellitus and hypothyroidism was admitted to hospital due to onset of proteinuria and oedema. Recurrent eczema and diarrhea had been noted in the previous months. Laboratory results revealed nephrotic range proteinuria, hypoalbuminemia, haematuria, anaemia and thrombocytopenia with normal kidney function. All immunological markers tested including ANA, ANCA, anty GBM antibodies, C3, C4, CH50  were normal. Regulatory T cell count was within reference range. Standard steroid therapy was prescribed and due to lack of remission after 4 weeks, cyclosporine was introduced. Due to onset of neurological symptoms cyclosporine had to be withdrawn.

Results:

Genetical testing confirmed the diagnosis of IPEX revealing a deletion in the  terminal part of exon of the gene encoding FOXP3 (NM_014009). In preparation for BMT intensified immunosuppression (rituximab and sirolimus) was administered to alleviate symptoms of all immunological disorders. After  2 months of therapy (before BMT) complete remission of nephrotic syndrome was achieved. Extrarenal manifestations of immunological involvement ( seizures, eczema, diarrhea) markedly improved

Conclusions:

 Steroid resistant nephrotic syndrome concurrent with extrarenal  immunological symptoms requires genetic diagnosis of IPEX , a rare congenital abnormality of Treg lymphocytes. Prompt remission of proteinuria can be achieved with Rituximab and sirolimus