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Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD).

ABSTRACT: Autosomal recessive polycystic kidney disease (ARPKD) is a severe pediatric hepatorenal disorder with pronounced phenotypic variability. A substantial number of patients with early diagnosis reaches adulthood and some patients are not diagnosed until adulthood. Yet, clinical knowledge about adult ARPKD patients is scarce. Here, we describe forty-nine patients with longitudinal follow-up into young adulthood that were identified in the international ARPKD cohort study ARegPKD. Forty-five patients were evaluated in a cross-sectional analysis at a mean age of 21.4 (±3.3) years describing hepatorenal findings. Renal function of native kidneys was within CKD stages 1 to 3 in more than 50% of the patients. Symptoms of hepatic involvement were frequently detected. Fourteen (31%) patients had undergone kidney transplantation and six patients (13%) had undergone liver transplantation or combined liver and kidney transplantation prior to the visit revealing a wide variability of clinical courses. Hepatorenal involvement and preceding complications in other organs were also evaluated in a time-to-event analysis. In summary, we characterize the broad clinical spectrum of young adult ARPKD patients. Importantly, many patients have a stable renal and hepatic situation in young adulthood. ARPKD should also be considered as a differential diagnosis in young adults with fibrocystic hepatorenal disease.

SUBMITTER: Burgmaier K

PROVIDER: S-EPMC6538621 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD).

Burgmaier Kathrin K Kilian Samuel S Bammens Bert B Benzing Thomas T Billing Heiko H Büscher Anja A Galiano Matthias M Grundmann Franziska F Klaus Günter G Mekahli Djalila D Michel-Calemard Laurence L Milosevski-Lomic Gordana G Ranchin Bruno B Sauerstein Katja K Schaefer Susanne S Shroff Rukshana R Sterenborg Rosalie R Verbeeck Sarah S Weber Lutz T LT Wicher Dorota D Wühl Elke E Dötsch Jörg J Schaefer Franz F Liebau Max C MC

Scientific reports 20190528 1

Autosomal recessive polycystic kidney disease (ARPKD) is a severe pediatric hepatorenal disorder with pronounced phenotypic variability. A substantial number of patients with early diagnosis reaches adulthood and some patients are not diagnosed until adulthood. Yet, clinical knowledge about adult ARPKD patients is scarce. Here, we describe forty-nine patients with longitudinal follow-up into young adulthood that were identified in the international ARPKD cohort study ARegPKD. Forty-five patients ...[more]

PMID: 31138820

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Project description:BackgroundThere is a high prevalence of rare genetic disorders in the Middle East, and their study provides unique clinical and genetic insights. Autosomal recessive polycystic kidney disease (ARPKD) is one of the leading causes of kidney and liver-associated morbidity and mortality in Oman. We describe the clinical and genetic profile of cohort of ARPKD patients.MethodsWe studied patients with a clinical diagnosis of ARPKD (n = 40) and their relatives (parents (n = 24) and unaffected siblings (n = 10)) from 32 apparently unrelated families, who were referred to the National Genetic Centre in Oman between January 2015 and December 2018. Genetic analysis of PKHD1 if not previously known was performed using targeted exon PCR of known disease alleles and Sanger sequencing.ResultsA clinical diagnosis of ARPKD was made prenatally in 8 patients, 21 were diagnosed during infancy (0-1 year), 9 during early childhood (2-8 years) and 2 at later ages (9-13 years). Clinical phenotypes included polycystic kidneys, hypertension, hepatic fibrosis and splenomegaly. Twenty-four patients had documented chronic kidney disease (median age 3 years). Twenty-four out of the 32 families had a family history suggesting an autosomal recessive pattern of inherited kidney disease, and there was known consanguinity in 21 families (66%). A molecular genetic diagnosis with biallelic PKHD1 mutations was known in 18 patients and newly identified in 20 other patients, totalling 38 patients from 30 different families. Two unrelated patients remained genetically unsolved. The different PKHD1 missense pathogenic variants were: c.107C > T, p.(Thr36Met); c.406A > G, p.(Thr136Ala); c.4870C > T, p.(Arg1624Trp) and c.9370C > T, p.(His3124Tyr) located in exons 3, 6, 32 and 58, respectively. The c.406A > G, p.(Thr136Ala) missense mutation was detected homozygously in one family and heterozygously with a c.107C > T, p.(Thr36Met) allele in 5 other families. Overall, the most commonly detected pathogenic allele was c.107C > T; (Thr36Met), which was seen in 24 families.ConclusionsMolecular genetic screening of PKHD1 in clinically suspected ARPKD cases produced a high diagnostic rate. The limited number of PKHD1 missense variants identified in ARPKD cases suggests these may be common founder alleles in the Omani population. Cost effective targeted PCR analysis of these specific alleles can be a useful diagnostic tool for future cases of suspected ARPKD in Oman.

Dataset Information

Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD).

Publications

Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD).

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