ESPN 51th Annual Meeting

ESPN 2018


 
ISOLATED PROTEINURIA DUE TO FOCAL SEGMENTAL GLOMERULOSCLEROSIS ASSOCIATED WITH MUTATIONS IN THE LAMA5 GENE IN A BOY
LARISA PRIKHODINA 1 Larisa Prikhodina 2 Tatyana Nikishina 1 Ekaterina Stolyarevich 3 Patricia Povilaitite 4 Peter Shatalov 1

1- RESEARCH & CLINICAL INSTITUTE FOR PEDIATRICS, PIROGOV RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY, Moscow, Russia
2- RUSSIAN ACADEMY OF MEDICAL CONTINUOUS POSTGRADUATE EDUCATION, Moscow, Russia
3- MOSCOW CITY CLINICAL HOSPITAL № 52, Moscow, Russia
4- Public Health Agency, Laboratory of Experimental Pathomorphology, Rostov-on-Don, Russia
 
Introduction:

Isolated glomerular proteinuria can be the only clinical feature of genetically heterogeneous glomerulopathies in children. Laminin-α5, encoded by LAMA5 gene is the major noncollagenous component of the mature glomerular basement membrane (GBM). Mutations in the LAMA5 gene (MIM 601033) were described previously in a few cases of steroid-resistant nephrotic syndrome, but has not been reported as monogenic cause of isolated glomerular proteinuria.

Material and methods:

We report on a 9-year-old boy presenting with isolated nephrotic proteinuria since the age of 3 years. Targeted next-generation exom sequencing (NGS) covering 68 gene implicated in SRNS with confirmation by direct Sanger sequencing were applied.

Results:

The boy with persistent isolated proteinuria (1-2 g/L) was referred to our clinic for further evaluation. There was no family history of kidney disorders. He was born at full term with low birth weight (2300 g) due to intrauterine growth restriction. On admission he had nephrotic-range glomerular proteinuria (1200 mg/m2/d) without hypoalbuminemia, edema or extrarenal disorders. The boy’ eGFR was 93 mL/min/1.73 m2. Renal ultrasound showed normal age-size kidneys with a lack of corticomedullary differentiation of parenchyma. The renal histology demonstrated focal segmental glomerulosclerosis (FSGS) with moderate interstitial fibrosis and tubular atrophy. Irregular thickening and lamellation of GBM with focal podocyte foot process effacement was described by electron microscopy. Targeted NGS identified compound heterozygous likely pathogenic missense mutations with unknown clinical significance: c.8389G>A, p.Val2797Met (dbSNP: rs200140507) in exon 62 and c.6206C>T, p.Pro2069Leu (dbSNP: rs201193135) in exon 47 in the LAMA5 gene. Therapy with ACE inhibitors (0.19 mg/kg/d) was administered to the patient with subsequent significant antiproteinuric effect (650 mg/m2/d) and stable eGFR (92 ml/min/1.73 m2) in 2 years of follow-up.

Conclusions:

We identify compound heterozygous mutations in the LAMA5 gene that may cause of isolated nephrotic proteinuria with thickening of GBM and secondary FSGS in a boy. Further studies are needed to evaluate the functional relevance of LAMA5 mutations in patients with isolated glomerular proteinuria and to determine their potential impact on the disease management and prognosis.