Diagnosing Alport Syndrome: Lessons from the Pediatric Ward

Abstract

Background: Alport syndrome is a rare inheritable kidney disease frequently leading to end-stage kidney disease in young adults. Patients could benefit from early recognition of the disease. In several children with Alport syndrome, a parent was noticed to have renal symptoms attributed to another renal disease. Aim: To review the renal history of the closest family members of a cohort of pediatric patients with genetically proven Alport syndrome. Methods: The medical records of all children with genetically proven Alport syndrome identified at our pediatric nephrology department in the last 20 years were reviewed, with focus on the medical history of affected parents. Results: Twenty-three children with Alport syndrome from 21 different families were identified. Eight of 21 probands had family member(s) with renal symptoms attributed to other diseases. In these, a type IV collagen mutation was determined only after the manifestation of Alport syndrome in their child. One proband presented atypically with acute membrano-proliferative glomerulo-nephritis. Only 3 out of 8 probands with a known family history of Alport syndrome had been intentionally screened for this disease. A COL4A5 mutation was found in 18 probands, COL4A3 in 2, and COL4A4 in 1. Each family showed private mutations; 17 out of 21 mutations were novel. Conclusions: Atypical presentation of Alport syndrome was quite common in mothers of our pediatric patients. To enable earlier diagnosis of Alport syndrome, nephrologists should look for a positive diagnosis in any patient with persistent renal symptoms, especially if there is a positive family history of (any) renal disease.

Features of Autosomal Recessive Alport Syndrome: A Systematic Review

“…Therefore, this analysis finally included 26 eligible articles with 148 patients (Figure 1) [7,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48]. The respective characteristics of included studies are summarized in Table 1.…”

Novel COL4A5 mutation in preimplantation genetic diagnosis of a patient with Alport syndrom

“…Previous studies have shown that most pediatric patients diagnosed with AS have atypical clinical manifestations from their parents and it is di cult to detect AS patients in time (Vos et al, 2018); therefore, nephrologists should focus on the emergence of patients with unexplained hematuria, proteinuria, or renal failure and determine whether there is a positive family history of kidney disease. Patients with XLAS are not uncommon in clinical practice, with around one case of X-linked AS patients in every 50,000 newborns (Vos et al, 2018). There is still no cure and the prognosis is poor and often progresses to endstage renal failure.…”

Síndrome de Alport: una genómica para tener presente

“…El síndrome de Alport es la segunda causa monogénica más común de enfermedad renal crónica (ERC) después de la poliquistosis renal autosómica dominante (14) . Genéticamente, en estudios de poblaciones se encuentra predominio en mutaciones COL4A5 en relación a COL4A3 y COL4A4, respectivamente (22) . La clínica primordialmente se caracteriza por hematuria persistente, pero de acuerdo al sexo es posible encontrar predominio de hematuria microscópica en todos los casos masculinos y en las pacientes femeninas se caracteriza aproximadamente el 98% por hematuria y el 73 % hematuria y proteinuria.…”