ESPN 50th Annual Meeting

ESPN 2017


 
NPHS2-ASSOCIATED STEROID-RESISTANT NEPHROTIC SYNDROME IN A BOY WITH STEROID SULFATASE DEFICIENCY-X-LINKED RECESSIVE ICHTHYOSIS
LARISA PRIKHODINA 1 LARISA PRIKHODINA 2 MARINA LEBEDENKOVA 1 TATYANA NIKISHINA 1 TATYANA LEPAEVA 1 EKATERINA STOLYAREVICH 3 PATRICIA POVILAITITE 4 PETER SHATALOV 1

1- Research Institute of Pediatrics, Pirogov Russian National Research Medical University, Moscow, RUSSIAN FEDERATION
2- Russian Academy of Medical Continuous Postgraduate Education, Moscow, RUSSIAN FEDERATION
3- Moscow City Clinical Hospital № 52, Moscow, RUSSIAN FEDERATION
4- Public Health Agency, Laboratory of Experimental Pathomorphology, Rostov-on-Don, RUSSIAN FEDERATION
 
Introduction:

Steroid-resistant nephrotic syndrome (SRNS) is a genetically heterogeneous glomerulopathy progressed to end-stage of renal disease (ESRD) during childhood or adolescence.  X-linked ichthyosis is a rare inherited disorder due to steroid sulfatase deficiency (MIM #308100). Very few cases of SRNS associated with X-linked recessive ichthyosis were described, but molecular genetic basis of SRNS was not studied yet.

 

Material and methods:

We report on a 11-year-old boy presenting with SRNS since age of 7 years with an underlying ichthyotic skin since birth.

Results:

The boy with SRNS and early-onset ichthyosis was referred to our clinic for further evaluation. On admission he had proteinuria (1.2 g/d), hypoalbuminemia (27 g/L) without oedema, normal blood pressure (110/60 mm Hg) and kidney function (eGFR 176.5 mL/min/1.73 m2). The boy had also severe hyperkeratosis. Renal ultrasound showed enlarged kidneys with bilateral diffuse hyperechogenicity of parenchyma. Kidney histopathology revealed focal segmental glomerulosclerosis with moderate interstitial fibrosis and tubular atrophy. Diffuse foot process effacement in podocytes was described by electron microscopy. Targeted next-generation sequencing covering 68 genes implicated in SRNS identified known heterozygous compound mutations c.890C>T (p.Ala297Val, rs199506378) in exon 8 and c.686G>A (p.Arg229Gln, rs61747728) in exon 5 in the NPHS2 gene, associated with of autosomal recessive SRNS, type 2 (MIM #600995). Copy number variation analysis revealed novel hemizygous deletion in the STS gene on chromosome Xp22.31 (6527321-8088112)x0 (Z-score <-3.2), confirming the diagnosis of X-linked recessive ichthyosis (MIM #308100). Therapy with ACE inhibitors was administered to the patient to prevent potential progression to ESRD. After 2 years of follow-up the boy had the same extent of proteinuria (1.5 g/d), and his renal function remains unimpaired (eGFR 123.5 ml/min/1.73 m2).

 

Conclusions:

We presented the case of NPHS2-associated SRNS in a boy with steroid sulfatase deficiency-X-linked ichthyosis caused by STS mutation. Digenic inheritance of NPHS2 and STS mutations in this case might have modifier effects with unclear molecular pathogenicity causing an uncommon clinical phenotype.