Unusual clinical outcome of primary Hyperoxaluria type 1 in Tunisian patients carrying 33_34InsC mutation

Abstract

BackgroundPrimary hyperoxaluria type 1 (PH1), is a rare and heterogeneous disease and one of major causes of renal insufficiency in Tunisia, caused by mutations in the AGXT gene. 33-34InsC mutation, was mainly described in children with a severe clinical feature leading to early death, but it was uncommonly reported in adult patients.MethodsCommon mutations in AGXT were tested using PCR/RFLP technique in 111 patients (68 adult, 43 children) with suspected PH1.ResultsWe described 16 cases (eight adult and eight children) with a 33-34InsC mutation with a median age of 24 years [6 months - 73 years]. All children were in end stage renal disease (ESRD) at the median age of 3 years due to lithiasis and/or nephrocalcinosis. Unfortunately, 75% of them died with a median age of 2.5 years. For the majority of adults only spontaneous elimination of urolithiasis were noted, 37.5% preserved until now a normal renal function and 62.5% of them reached ESRD at the median age of 55.8 ± 12.31 years old.ConclusionIn this study 33-34InsC mutation gives a controversial clinical effect in children and adults. The implication of other genetic and/or environmental factors can play a crucial role in determining the ultimate phenotype.

Still diagnosed too late and under-recognized? A first comprehensive report on primary hyperoxaluria from Poland

“…Whereas patient F4.3 developed infantile oxalosis and F4.1 typical adolescent form of the disease, patients F4.2 and F4.4 remained asymptomatic till adulthood. This phenomenon of diverse intrafamilial disease expression in PH1 was already reported but the underlying factors are still unclear [36][37][38][39].…”

Case series and literature review of primary hyperoxaluria type 1 in Chinese patients

“…There are reports of ESRD reaching the age of 70. The above heterogeneity of genotype and phenotype supports the idea that other enzymes may be involved in oxalate synthesis, or that glyoxylate metabolism may be regulated through interactions with modifying genes and/or environmental factors [ 48 , 51 ]. However, in general, patients with urolithiasis as the main presentation were significantly younger than other mutation types when they carried frameshift mutations [ 22 ].…”

“…Therefore, PH1 patients with this mutation tend to have a more severe phenotype, and the homozygous state for this mutation occurs mainly in pediatric cases and is rarely reported in late-onset cases [ 48 – 50 ]. Mbarek IB et al reported eight children with PH1, all homozygous for the c.33dupC mutation, 75% died of the disease at a median age of 2.5 years, and other patients also had severe urolithiasis, all of which had developed ESRD [ 51 ]. Murad, H et al reported 12 pediatric patients with PH1 homozygous for the c.33dupC mutation, 10 of whom suffered from renal failure or died.…”

Four novel variants identified in primary hyperoxaluria and genotypic and phenotypic analysis in 21 Chinese patients

“…In a sense, differences between the two groups suggested that there may be still some variations in the mild group that can confer AGT activity, which requires further functional expression research. Moreover, the ultimate phenotype and prognosis of patients may be affected by the age of diagnosis and clinical intervention, environmental factors and other variants from modifying genes, and just because of this, patients carrying the same variants may have great phenotypic heterogeneity ( Mbarek et al, 2017 ).…”