Congenital nephrotic syndrome of the finnish type in the Republic of Belarus: clinical case report and analysis of molecular genetic features

BACKGROUND . Congenital nephrotic syndrome (CNS) is a rare autosomal recessive kidney disorder that manifests within the first three months of life. It is characterized by massive proteinuria, hypoalbuminemia, hypercholesterolemia, edema, steroid resistance and inevitable progression to end-stage chronic kidney disease (ESCKD). In 85 % of cases CNS is a monogenic disease. THE AIM : To present a clinical case of genetically confirmed CNS of the Finnish type in the Republic of Belarus. PATIENTS AND METHODS . A male infant from the first pregnancy and first full-term birth was examined. On the third day after birth testicular hydrocele, proteinuria and hypoalbuminemia were diagnosed and persisted despite transfusions of 20 % albumin solution. Further examination revealed persistent arterial hypertension and elevated levels of thyroid-stimulating hormone. At the age of 5 months bilateral nephrectomy was performed, followed by various forms of renal replacement therapy (peritoneal dialysis, hemodialysis, and kidney transplantation from a deceased donor). Molecular genetic testing identified two mutations in the NPHS1 gene in a compound heterozygote. RESULTS . Mutations of the NPHS1 gene are associated with CNS of the Finnish type (Nephrotic syndrome, type 1, OMIM 256300). The identified variants NM_004646: exon18:c.2335-1G>A and NM_004646:exon8:c.C847T:p.Q283* differ from the ‘Finnish mutations’ Fin-major and Fin-minor and are in trans. The patient was also found to be homozygous for the p.R229Q polymorphism at locus rs61747728 of the NPHS2 gene. Morphological examination of the nephrectomy materials revealed changes characteristic of CNS of the Finnish type. CONCLUSIONS . In this clinical case a child with compound heterozygous mutation in the NPHS1 gene and a homozygous rare polymorphic variant in the NPHS2 gene exhibited a severe course of CNS of the Finnish type with rapid progression to ESCKD. Molecular genetic testing confirmed the diagnosis of CNS of the Finnish type and allowed avoiding the administration of immunosuppressive therapy. Additionally, the results of molecular genetic analysis of the parents should be taken into account when planning future pregnancies.