Infantile nephrotic syndrome secondary to cytomegalovirus infection in a 7-month-old girl: resolution with ganciclovir

Background: Pathogenic variants in single genes encoding podocyte-associated proteins have been implicated in about 30% of steroid resistant nephrotic syndrome (SRNS) patients in children. However, LAMA5 gene biallelic variants have been identified in only 7 patients so far, and most are missense variants of unknown significance. Furthermore, no functional analysis had been conducted for all but one of these variants. Here, we report three patients with LAMA5 gene biallelic truncating variants manifesting infantile nephrotic syndrome and one SRNS case with biallelic LAMA5 missense variants. Methods: We conducted comprehensive gene screening of Japanese patients with severe proteinuria. Using targeted next-generation sequencing, 62 podocyte-related genes were screened in 407 unrelated patients with proteinuria. For the newly discovered LAMA5 variants, we conducted in vitro heterotrimer formation assays. Results: Biallelic truncating variants in the LAMA5 gene (NM_005560) were detected in 3 patients from 2 families. All patients presented with proteinuria within 6 months of age. Patients 1 and 2 were siblings possessing a nonsense variant (c.9232C>T, p.(Arg3078*)) and a splice site variant (c.1282+1G>A) that led to exon 9 skipping and a frameshift. Patient 3 had a remarkable irregular contour of the glomerular basement membrane. She was subsequently found to have a nonsense variant (c.8185C>T, p.(Arg2720*)) and the same splice site variant in patients 1 and 2. By in vitro heterotrimer formation assays, both truncating variants produced smaller laminin α5 proteins that nevertheless formed trimers with laminin β1 and γ1 chains. Patient 4 showed SRNS at the age of eight and carried compound heterozygous missense variants (c.1493C>T, p.(Ala498Val) and c.8399G>A, p.(Arg2800His)). Conclusions: Our patients showed clear evidence of biallelic LAMA5 truncating variants causing infantile nephrotic syndrome. We also discerned the clinical and pathological characteristics observed in LAMA5-related nephropathy. LAMA5 variant screening should be performed in congenital/infantile nephrotic syndrome patients.

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Infantile nephrotic syndrome, immunodeficiency and adrenal insufficiency—a rare cause: Answers

Pediatric Nephrology ◽

10.1007/s00467-021-05377-1 ◽

2022 ◽

Author(s):

Georgie Mathew ◽

M. S. Yasmeen ◽

R. V. Deepthi ◽

Meenakshi Swain ◽

Avinash Vattam ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Adrenal Insufficiency ◽

Infantile Nephrotic Syndrome

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Non-genetic congenital and infantile nephrotic syndrome: New diagnostic and therapeutic management

Archives de Pédiatrie ◽

10.1016/j.arcped.2017.10.012 ◽

2017 ◽

Vol 24 (12) ◽

pp. 1331

Author(s):

J.-M. de Guillebon de Resnes ◽

G. Deschênes ◽

O. Niel

Keyword(s):

Nephrotic Syndrome ◽

Therapeutic Management ◽

Infantile Nephrotic Syndrome

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A cross-sectional nationwide survey of congenital and infantile nephrotic syndrome in Japan

10.21203/rs.3.rs-22986/v1 ◽

2020 ◽

Author(s):

Yuko Hamasaki ◽

Riku Hamada ◽

Masaki Muramatsu ◽

Shinsuke Matsumoto ◽

Kunihiko Aya ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Kidney Disease ◽

Congenital Nephrotic Syndrome ◽

Nationwide Survey ◽

The Other ◽

End Stage Kidney Disease ◽

Cross Sectional ◽

Infantile Nephrotic Syndrome ◽

Finnish Type ◽

End Stage

Abstract Background: Congenital nephrotic syndrome (CNS) and infantile nephrotic syndrome (INS) cause substantial morbidity and mortality. In Japan, there is a lack of knowledge regarding the characteristics of CNS and INS. This study aimed to clarify the characteristics of CNS and INS in Japan.Methods: This cross-sectional nationwide survey obtained data from 44 institutions in Japan managing 92 patients with CNS or INS by means of two survey questionnaires sent by postal mail. Patients aged <16 years by 1 April 2015, with a diagnosis of CNS or INS, were included in this study. The primary outcome was end-stage kidney disease.Results: A total of 83 patients with CNS or INS were analyzed. The most frequent disease type was non-Finnish (60.2%); 33 patients (39.8%) had Finnish type. Among those with non-Finnish-type disease, 26 had no syndrome and 24 had a syndrome, of which the most frequent was Denys–Drash syndrome (70.8%). Patients with non-Finnish-type disease with syndrome showed the earliest progression to end-stage kidney disease compared with the other two groups, whereas patients with non-Finnish-type disease without syndrome progressed more slowly compared with the other two groups. In the Finnish-type group, the disease was diagnosed the earliest; a large placenta was reported more frequently; genetic testing was more frequently performed (93.8%); mental retardation was the most frequent extra-renal symptom (21.2%); and thrombosis and infection were more frequent compared with the other groups. Patients with non-Finnish-type disease with syndrome had a higher frequency of positive extra-renal symptoms (79.2%), the most common being urogenital symptoms (54.2%). Treatment with steroids and immunosuppressants was more frequent among patients with non-Finnish-type disease without syndrome. Two patients with non-Finnish-type disease without syndrome achieved complete remission. In all groups, unilateral nephrectomy was performed more often than bilateral nephrectomy and peritoneal dialysis was the most common renal replacement therapy.Conclusions: The present epidemiological survey sheds light on the characteristics of children with CNS and INS in Japan. A high proportion of patients underwent genetic examination, and patient management was in accord with current treatment recommendations and practices.Trial registration: Not applicable.

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