ESPN 51th Annual Meeting

ESPN 2018


 
PROTEINURIA IN CHILDREN FROM A NATIONAL ALPORT SYNDROME COHORT – DEFINED BY NEW ALPORT SYNDROME CLASSIFICATION
Olga Bielska 1 Beata S. Lipska-Ziętkiewicz 2 Dominika Kuleszo 2 Maria Szczepańska 4 Dagmara Roszkowska-Bjanid 4 Małgorzata Pańczyk-Tomaszewska 3 Elżbieta Kuźma-Mroczkowska 3 Katarzyna Taranta-Janusz 5 Iwona Jadeszko 5 Janina Taraszkiewicz 6 Danuta Ostalska-Nowicka 7 Alina Rabiega 7 Katarzyna Jobs 8 Judyta Mews 8 Przemysław Sikora 11 Anna Wieczorkiewicz-Plaza 11 Marcin Tkaczyk 14 Anna Jander 14 Danuta Zwolińska 10 Kinga Musiał 10 Dorota Drożdż 12 Anna Moczulska 12 Elżbieta Jarocka-Cyrta 13 Małgorzata Śniadecka 13 Roman Stankiewicz 9 Aleksandra Żurowska 1

1- Department of Pediatrics, Nephrology and Hypertension, Medical University of Gdansk, Gdansk, Poland
2- Department of Biology and Medical Genetics, Clinical Genetics Unit, Medical University of Gdansk, Gdansk, Poland
3- Department of Pediatrics and Nephrology, Medical University of Warsaw, Warsaw, Poland
4- Department and Clinic of Pediatrics, Medical University of Silesia, Zabrze, Poland
5- Department of Paediatrics and Nephrology, Medical University of Bialystok, Bialystok, Poland
6- Regional Center of Pediatrics and Oncology, Chorzow, Poland
7- Department of Pediatric Cardiology and Nephrology, Poznan University of Medical Sciences, Poznan, Poland
8- Department of Paediatrics, Paediatric Nephrology and Allergology at the Military Institute of Medicine, Warsaw, Poland
9- Department of Pediatrics and Nephrology, Ludwik Rydygier Hospital, Torun, Poland
10- Department of Paediatric Nephrology, Wroclaw Medical University, Wroclaw, Poland
11- Department of Pediatric Nephrology, Medical University of Lublin, Lublin, Poland
12- Department of Pediatric Nephrology, Jagiellonian University, Cracow, Poland
13- Department of Pediatrics, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland
14- Department of Pediatrics, Immunology and Nephrology, PMMH-RI, Lodz, Poland
 
Introduction:

A National Alport Syndrome Registry was established in 2017 involving 13 paediatric nephrology centres in Poland. 

Objectives.

Recognition of pathogenic variants in COL4A3-5 genes in Polish children with familial haematuria.

Establishing the frequency of proteinuria in children within the 3 types of Alport syndrome (AS).

Material and methods:

Clinical and histopathological data of children with persistent glomerular hematuria was collected into an online database. Proteinuria was defined as urine protein-creatinine ratio >0.2 mg/mg. Simultaneous analysis of encoding sequences of COL4A3-5 genes was performed by NGS technology. Genetic findings were classified according to the new classification of Alport syndrome, categorizing genetic diseases of collagen IV α345 into 3 types of AS: X-linked, autosomal, and digenic (Kashtan CE et al, Kidney Int 2018).

Results:

To date, 91 unrelated children (49girls, 42 boys) were identified at a median age of 11 (3-20) years. 79 children (87%) had a family history of haematuria. Pathogenic variants in COL4A3-5 genes were detected in 72 subjects (79% of total cohort and 85% with familial haematuria). Proteinuria was detected in 49% of children with identified COL4A3-5 pathogenic variants - in 73% of boys and 44% of girls with X-linked, 26% with autosomal and in one child with digenic AS. 

Inheritance

No (%)

Affected gene(s)

No

Genetic state

No

Proteinuria

No (%)

X-linked

 

48 (53%)

 

COL4A5

48

hemizygous (M)

heterozygous (F)

compound heterozygous (F)

22

25

1

16 (73%)

11 (44%)

1 (100%)

Autosomal

 

23 (25%)

COL4A3

or COL4A4

9

14

homozygous 

heterozygous

2

21

1 (50%)

5 (24%)

Digenic

1 (1%)

COL4A4 and A5

1

-

1

1 (100%)

Not

identified

19 (21%)

unknown

19

-

19

7 (37%)

 

Conclusions:

COL4A3-5 pathogenic variants were identified by NGS technology in 85% of Polish children with familial haematuria.

Proteinuria was present in a significant proportion of children within all genetic types of Alport syndrome.