Primary hyperoxaluria type 1 results from alanine:glyoxylate aminotransferase deficiency. Due to genotype/phenotype heterogeneity in this autosomal recessive disorder, the renal outcome is difficult ...to predict in these patients and the long-term impact of conservative management in children is unknown. We report here a multicenter retrospective study on the renal outcome in 27 affected children whose biological diagnosis was based on either decreased enzyme activity or identification of mutations in the patient or his siblings. The median age at first symptoms was 2.4 years while that at initiation of conservative treatment was 4.1 years; 6 children were diagnosed upon family screening. The median follow-up was 8.7 years. At diagnosis, 15 patients had an estimated glomerular filtration rate (eGFR) below 90, and 7 children already had stage 2–3 chronic kidney disease. The median baseline eGFR was 74, which rose to 114 with management in the 22 patients who did not require renal replacement therapy. Overall, 20 patients had a stable eGFR, however, 7 exhibited a decline in eGFR of over 20 during the study period. In a Cox regression model, the only variable significantly associated with deterioration of renal function was therapeutic delay with a relative risk of 1.7 per year. Our study strongly suggests that early and aggressive conservative management may preserve renal function of compliant children with this disorder, thereby avoiding dialysis and postponing transplantation.
Cerebello-oculo-renal syndrome (CORS), also called Joubert syndrome type B, and Meckel (MKS) syndrome belong to the group of developmental autosomal recessive disorders that are associated with ...primary cilium dysfunction. Using SNP mapping, we identified missense and truncating mutations in RPGRIP1L (KIAA1005) in both CORS and MKS, and we show that inactivation of the mouse ortholog Rpgrip1l (Ftm) recapitulates the cerebral, renal and hepatic defects of CORS and MKS. In addition, we show that RPGRIP1L colocalizes at the basal body and centrosomes with the protein products of both NPHP6 and NPHP4, known genes associated with MKS, CORS and nephronophthisis (a related renal disorder and ciliopathy). In addition, the RPGRIP1L missense mutations found in CORS individuals diminishes the interaction between RPGRIP1L and nephrocystin-4. Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Nalaganje filtrov
Noben zadetek ni izbran!
Prosimo, izberite zadetke, ki jih želite izvoziti.
Iskanje je bilo uspešno shranjeno.
Urejanje
Iskanja ni bilo mogoče shraniti.
Shranjena iskanja si lahko ogledate v seznamu Moja iskanja.
Spremembe v shranjenem iskanju so uspešno shranjene.
Shrani iskanje
Vnos na polico
Noben zadetek ni izbran!
Dodajanje gradiva na polico je uspelo.
Dodajanje gradiva na polico je le deloma uspelo.
Dodajanje gradiva na polico je v celoti spodletelo.
Dodajanje gradiva na polico ni bilo potrebno.
Prosimo, izberite zadetke, ki jih želite dati na polico!
Na polico so bili uspešno dodani naslednji zapisi:
Na polico so bili uspešno dodani naslednji zapisi:
Vnosi, pri katerih je dodajanje na polico spodletelo:
Dodajanje na polico ni uspelo za vse izbrane vnose:
Vsa izbrana gradiva so že na polici.
Duplikat
Dosežena omejitev
Urejanje
Napaka
Urejanje
Dodajanje
Urejanje
Sprememba statusa
Opozorilo s to iskalno zahtevo že obstaja. Prosimo, preverite seznam Moja opozorila.
Imate že 10 aktivnih opozoril.
Pri urejanju opozorila ni bilo nobenih sprememb.
Pri dodajanju in/ali urejanju opozorila se je pojavila napaka. Prosimo, poskusite ponovno.
opac.user.alert.dialog.alert_success.info
Opozorilo je bilo uspešno dodano in aktivirano.
Spremembe v nastavitvah opozorila so uspešno shranjene.