Mutational analysis of the PLCE1 gene in steroid-resistant nephrotic syndrome

International audienceBackground: Mutations in the PLCE1 gene encoding phospholipase C epsilon 1 (PLCε1) have been recently described in patients with early-onset nephrotic syndrome (NS) and diffuse mesangial sclerosis (DMS). In addition, two cases of PLCE1 mutations associated with focal segmental glomerulosclerosis (FSGS) and later NS onset have been reported. Methods: In order to better assess the spectrum of phenotypes associated with PLCE1 mutations, we performed mutational analysis in a worldwide cohort of 139 patients (95 familial cases belonging to 68 families and 44 sporadic cases) with steroid-resistant NS presenting at a median age of 23.0 months (range 0-373). Results: We identified homozygous or compound heterozygous mutations in 33% (8/24) of DMS cases. PLCE1 mutations were found in 8% (6/78) of FSGS cases without NPHS2 mutations. Nine were novel mutations. No clear genotype-phenotype correlation was observed, with either truncating or missense mutations detected in both DMS and FSGS, and leading to a similar renal evolution. Surprisingly, 3 unaffected and unrelated individuals were also found to carry the homozygous mutations identified in their respective families. Conclusion: PLCE1 is a major gene of DMS and is mutated in a non-negligible proportion of FSGS cases without NPHS2 mutations. Although we did not identify additional variants in 19 candidate genes (16 other PLC genes, BRAF, IQGAP1 and NPHS1), we speculate that other modifier genes or environmental factors may play a role in the renal phenotype variability observed in individuals bearing PLCE1 mutations. This observation needs to be considered in the genetic counselling offered to patients

COVID-19 in pediatric nephrology centers in Turkey

Background/aim: There is limited data on COVID-19 disease in children with kidney disease. We aimed to investigate the characteristics and prognosis of COVID-19 in pediatric nephrology patients in Turkey. Materials and methods: This was a national, multicenter, retrospective cohort study based on an online survey evaluating the data between 11th March 2020 and 11th March 2021 as an initial step of a detailed pediatric nephrology COVID-19 registry. Results: Two hundred and three patients (89 girls and 114 boys) were diagnosed with COVID-19. One-third of these patients (36.9%) were between 10–15 years old. Half of the patients were on kidney replacement therapy: kidney transplant (KTx) recipients (n = 56, 27.5%), patients receiving chronic hemodialysis (n = 33, 16.3%) and those on peritoneal dialysis (PD) (n = 18, 8.9%). Fifty-four (26.6%) children were asymptomatic. Eighty-two (40.3%) patients were hospitalized and 23 (28%) needed intensive care unit admission. Fifty-five percent of the patients were not treated, while the remaining was given favipiravir (20.7%), steroid (16.3%), and hydroxychloroquine (11.3%). Acute kidney injury developed in 19.5% of hospitalized patients. Five (2.4%) had MIS-C. Eighty-three percent of the patients were discharged without any apparent sequelae, while 7 (3.4%) died. One hundred and eight health care staff were infected during the study period. Conclusion: COVID-19 was most commonly seen in patients who underwent KTx and received HD. The combined immunosuppressive therapy and frequent exposure to the hospital setting may increase these patients’ susceptibility. Staff infections before vaccination era were alarming, various precautions should be taken for infection control, particularly optimal vaccination coverage

ÇOCUKLARDA ÜRİNER SİSTEM TAŞLARININ ETİYOPATOGENEZİ VE KLİNİK SEYRİ

Giriş-amaç: Üriner sistem taş hastalığı yönünden endemik ülkeler arasında olan ülkemizde, çocukluk çağı taş hastalığı ile ilgili çalışmalar sınırlıdır. Kliniğimizde üriner sistem taş hastalığı nedeniyle izlenen hastaların demografik ve klinik verilerinin belirlenmesi, taş hastalığının etiyolojisinin değerlendirilmesi, tanı yaklaşımı ve tedavi yöntemlerinin prognoza etkisinin karşılaştırılması amaçlanmıştır. Materyal-metod: İstanbul Üniversitesi, İstanbul Tıp Fakültesi, Çocuk Nefrolojisi Bilim Dalı’na 1999-2009 yılları arasında başvuran ve üriner sistem taş hastalığı tanısı ile izlenen hastaların verileri geriye dönük olarak incelendi. Bulgular: 403 hastanın (218 erkek, 185 kadın) % 91,3'ü Marmara bölgesinde ikamet ediyordu. Ortalama başvuru yaşı 52,8 ay (1-192 ay), başvuru anında sıklık sırasına göre %49,4 ağrı, %26,3 idrar yolu enfeksiyonu, %22,5 taş düşürme, %18,6 makroskopik hematüri mevcuttu. Çalışma grubunda %51,6 olguda taş oluşum riski oluşturabilecek metabolik bozukluk, %21,3 olguda ise yapısal anomali mevcuttu. Taş analizleri yapılan olgularda %60,5 oranında kalsiyum taşı belirlendi. Metabolik bozukluklar içinde en sık bulgu hiperkalsiüri (n:171; %48,4), sonra sırasıyla hipositratüri (n:92; %32,3), hiperürikozüri (n:41; %20,1), hiperoksalüri (n:56; %19,7) ve sistinüri (n:20; %18,7) saptandı. Tüm hastalar diyet, sıvı alımı artırılması ve tuz kısıtlamasını içeren konservatif tedavi önerildi. 131 vaka (%32,5) ise cerrahi olarak tedavi edildi, 205 vaka (%50,9) altta yatan metabolik bozukluklar için ilaç kullanıyordu. Konservatif tedavi alan hastaların %17,1'i iyileşme göstermezken, hastaların %4,7'sinde böbrek yetmezliği gelişti. Kırk dokuz hastada (%12,1) tekrarlayan idrar taşı vardı. Sonuç: Çalışmamızın sonuçları, metabolik değerlendirmenin ve yapısal araştırmaların çocukluk çağı üriner sistem taşı hastalığı için önemini desteklemektedir.</p

Steroid-induced psychosis in an adolescent: treatment and prophylaxis with risperidone

Steroid-induced psychotic disorder is one of the serious adverse effects of corticosteroid therapy and is characterized by hallucinations and delusions. While the mechanism is unclear, treatment of steroid psychosis involves dosage reduction or discontinuation of prednisone. In cases where this cannot be done, typical treatment involves an antipsychotic medication. Although it is a well-known complication in adulthood, literature about steroid-induced psychotic disorder in children and adolescents is lacking. Here we report a 12-year-old case of steroid-induced psychotic disorder who was treated with an atypical antipsychotic, risperidone, and in whom the antipsychotic therapy was maintained because of continuation of her corticosteroid treatment for nephrotic syndrome. Pediatricians should be aware of this rare problem when prescribing corticosteroids in this age group. To our knowledge, this is the first reported case of steroid-induced psychosis successfully treated with risperidone in an adolescent with nephrotic syndrome