Primary Hyperoxaluria Type 1 in 18 Children: Genotyping and Outcome

Abstract

Background. Primary hyperoxaluria belongs to a group of rare metabolic disorders with autosomal recessive inheritance. It results from genetic mutations of the AGXT gene, which is more common due to higher consanguinity rates in the developing countries. Clinical features at presentation are heterogeneous even in children from the same family; this study was conducted to determine the clinical characteristics, type of AGXT mutation, and outcome in children diagnosed with PH1 at a tertiary referral center in Oman. Method. Retrospective review of children diagnosed with PH1 at a tertiary hospital in Oman from 2000 to 2013. Result. Total of 18 children were identified. Females composed 61% of the children with median presentation age of 7 months. Severe renal failure was initial presentation in 39% and 22% presented with nephrocalcinosis and/or renal calculi. Family screening diagnosed 39% of patients. Fifty percent of the children underwent hemodialysis. 28% of children underwent organ transplantation. The most common mutation found in Omani children was c.33-34insC mutation in the AGXT gene. Conclusion. Due to consanguinity, PH1 is a common cause of ESRD in Omani children. Genetic testing is recommended to help in family counseling and helps in decreasing the incidence and disease burden; it also could be utilized for premarital screening.

Epidemiology and Outcome of CKD in Omani Children

“…The second most common etiology of CKD in the current study is hereditary renal conditions, including familial focal segmental glomerulosclerosis, congenital nephrotic syndrome, polycystic kidney disease, and primary hyperoxaluria. This finding was also seen in other studies from Oman19, 20 and from the Middle East 9, 11, 21. These findings are expected, as consanguinity is common in these countries.…”

A novel nonsense variant of the AGXT identified in a Chinese family: special variant research in the Chinese reference genome

“…The variants in the AGXT gene cause PH1 [ 1 , 27 ], while variants in GRHPR result in PH2 [ 28 , 29 ] and the deficiency in HOGA1 leads to PH3 [ 30 ]. Accordingly, sequencing the whole gene AGXT and detecting the variants has become highly recommended for the diagnosis of PH1 at the earlier stage [ 8 , 11 , 16 ]. Although no confirmed variant hot spots in gene AGXT have been found [ 9 ], more than 190 variants have been reported worldwide in different ethnic populations [ 4 ].…”

“…In the present report, a six year old boy with confirmed PH1was treated conservatively for five months. Two variant points in gene AGXT were identified in his family by Whole Exon Sequencing (WES), including a novel nonsense variant from his mother and a missense variant from his father [ 6 , 15 , 16 ]. To update PH1 genotypes in Chinese population and elucidate the AGXT variants spectrum in the local population, we built a local reference genome by collecting genomes from 300 healthy Chinese Han people.…”

Long-Term Effect of Nephrocalcinosis on Renal Function and Body Growth Index in Children: A Retrospective Single Center Study

“…Additionally, few studies have been conducted on the identification and underlying causes of NC and on whether it has any impact on body growth and renal function in children (10,18). Al-Riyami MS et al found severe renal failure as initial presentation among 39% of children with primary hyperoxaluria type 1 with nephrocalcinosis in comparison with 22% among those without it (19). Hence, the present retrospective study was carried out to examine the causes of NC and its effect on renal function and body growth as well as its follow-up findings in children.…”