Oral Manifestations of a Pediatric Patient with Primary Hyperoxaluria Type 1: A Case Report

Seunghyun Oh,Hyuntae Kim,Teo Jeon Shin,Hong-Keun Hyun,Young-Jae Kim,Jung-Wook Kim,Ki-Taeg Jang,Ji-Soo Song Asia Association for Disability and Oral Health 2022 대한장애인치과학회지 Vol.18 No.1

Primary hyperoxaluria is a rare, genetic metabolic disorder caused by deficiency of alanine-glyoxylate aminotransferase, which results in recurrent kidney stones, parenchymal renal damage, and end-stage renal disease. Patients with primary hyperoxaluria have accumulation of calcium oxalate crystal in most part of the oral cavity, such as bone, periodontal tissues, dentin, cementum, and dental pulp. This report describes a case of 6-year-old boy who was diagnosed with primary hyperoxaluria. For treatment of primary hyperoxaluria, he underwent pre-emptive liver transplant and was on continuous hemodialysis. He has been taking multiple medications, including aspirin. In oral and radiographic examination, generalized root resorption, multiple radiolucent lesions and severe periodontitis were observed. These conditions caused dental pain, worsened tooth mobility, progressive tooth loss and mesial titling of permanent molars. Periodontal treatments including dental scaling were performed under tapered administration of aspirin and prescription of prophylactic antibiotics. Early diagnosis and careful management of the oral conditions would be necessary with the goal of minimizing progression of periodontitis and alveolar bone resorption.

Primary Hyperoxaluria Screening and Monitoring: Quantitative Measurement of Plasma Oxalate by Gas Chromatography-Mass Spectrometry With High Sensitivity

Yazdanpanah Mehrdad,Cameron Jessie,Chappel Chandra,Yuan Libin 대한진단검사의학회 2024 Annals of Laboratory Medicine Vol.44 No.3

Background: Plasma oxalate measurements can be used for the screening and therapeutic monitoring of primary hyperoxaluria. We developed a gas chromatography-mass spectrometry (GC-MS) assay for plasma oxalate measurements with high sensitivity and suitable testing volumes for pediatric populations. Methods: Plasma oxalate was extracted, derivatized, and analyzed by GC-MS. We measured the ion at m/z 261.10 to quantify oxalate and the 13C2-oxalate ion (m/z: 263.15) as the internal standard. Method validation included determination of the linear range, limit of blank, limit of detection, lower limit of quantification, precision, recovery, carryover, interference, and dilution effect. The cut-off value between primary and non-primary hyperoxaluria in a pediatric population was analyzed. Results: The detection limit was 0.78 μmol/L, and the linear range was up to 80.0 μmol/L. The between-day precision was 5.7% at 41.3 μmol/L and 13.1% at 1.6 μmol/L. The carryover was <0.2%. The recovery rate ranged from 90% to 110%. Interference analysis showed that Hb did not interfere with plasma oxalate quantification, whereas intralipids and bilirubin caused false elevation of oxalate concentrations. A cut-off of 13.9 μmol/L showed 63% specificity and 77% sensitivity, whereas a cut-off of 4.15 μmol/L showed 100% specificity and 20% sensitivity. The minimum required sample volume was 250 μL. The detected oxalate concentrations showed interference from instrument conditioning, sample preparation procedures, medications, and various clinical conditions. Conclusions: GC-MS is a sensitive assay for quantifying plasma oxalate and is suitable for pediatric patients. Plasma oxalate concentrations should be interpreted in a clinical context.

Antiurolithic effect of olive oil in a mouse model of ethylene glycol-induced urolithiasis

Mohammed Alenzi,Shaik Rahiman,Bilal Ahmad Tantry 대한비뇨의학회 2017 Investigative and Clinical Urology Vol.58 No.3

Purpose: At present, commercially available antiurolithic drugs have more adverse effects than potential therapeutic or preventive effects with chronic use. With this in mind, the present study was designed to assess the antiurolithic effect of olive oil in a mouse model of ethylene glycol (EG)-induced urolithiasis. Materials and Methods: Adult albino mice were divided into 6 groups. Group I was fed the vehicle only. Group II was supplemented with 0.75% EG alone in drinking water during the experimental period to initiate deposition of calcium oxalate in kidneys, which leads to urolithiasis in animals. Groups III (olive oil control group) through V were fed olive oil orally at various doses during the experimental period. Group VI received cystone (750 mg/kg). Groups IV–VI additionally received 0.75% EG in drinking water ad libitum. SPSS ver.17.0 was used for statistical analysis. Results: The study results showed significantly higher levels of serum urea, uric acid, and creatinine (p<0.05) in group II than in groups III–VI and I. Administration of olive oil at different doses restored the elevated serum parameters in groups IV and V compared with group II. Urine and kidney calcium, oxalate, and phosphate levels in groups IV–VI were significantly lower (p<0.05) than in animals with EG-induced urolithiasis (group II). Group V mice showed a significant restoration effect on serum as well as urine and kidney parameters compared with group II. Conclusions: Supplementation with olive oil (1.7 mL/kg body weight) reduced and prevented the growth of urinary stones, possibly by inhibiting renal tubular membrane damage due to peroxidative stress induced by hyperoxaluria.

이식신의 기능상실이 동반된 일차성 과옥살산뇨증 1예

송은주 ( Eun Joo Song ),조장희 ( Jang Hee Cho ),윤영득 ( Young Deuk Yoon ),박자용 ( Ja Yong Park ),최지영 ( Ji Young Choi ),윤세희 ( Se Hee Yoon ),김연수 ( Yon Su Kim ),김찬덕 ( Chan Duck Kim ),김용림 ( Yong Lim Kim ),박선희 ( Sun 대한신장학회 2011 Kidney Research and Clinical Practice Vol.30 No.6

Primary hyperoxaluria is a rare disorder of glyoxylate metabolism in which hepatic enzyme deficiencies result in overproduction of oxalate. The resulting elevation of urinary oxalate excretion leads to recurrent urolithiasis and progressive nephrocalcinosis. End-stage renal disease frequently occurs and is accompanied by systemic oxalate deposition along with its harmful effects. With the rarity and various clinical heterogeneity of the disease, the high proportion of patients in whom diagnosis is made after advanced renal failure have developed it. On account of its high rate of graft loss associated with primary hyperoxaluria, isolated kidney transplantation has been replaced by combined liver/kidney transplantation. In this report, we describe a case of primary hyperoxaluria with kidney graft failure who had a history of recurrent renal stones.

Primary Hyperoxaluria in Korean Pediatric Patients

Yunsoo Choe,이지원,Ji Hyun Kim,Myung Hyun Cho,Seong Heon Kim,Joo Hoon Lee,Young Seo Park,Hee Gyung Kang,Il Soo Ha,Hae Il Cheong 대한소아신장학회 2019 Childhood kidney diseases Vol.23 No.2

Background: Primary hyperoxaluria (PH), a rare inborn error of glyoxylate meta bolism causing overproduction of oxalate, is classified into three genetic subgroups: type 1–3 (PH1–PH3) caused by AGXT, GRHPR , and HOGA1 gene mutations, respectively. We performed a retrospective case series study of Korean pediatric patients with PH. Methods: In total, 11 unrelated pediatric patients were recruited and their phenotypes and genotypes were analyzed by a retrospective review of their medical records. Results: Mutational analyses revealed biallelic AGXT mutations (PH1) in nine patients and a single heterozygous GRHPR and HOGA1 mutation in one patient each. The c.33dupC was the most common AGXT mutation with an allelic frequency of 44%. The median age of onset was 3 months (range, 2 months–3 years), and eight patients with PH1 presented with end stage renal disease (ESRD). Patients with two truncating mutations showed an earlier age of onset and more frequent retinal involvement than patients with one truncating mutation. Among eight PH1 patients presenting with ESRD, five patients were treated with intensive dialysis followed by liver transplantation (n=5) with/without subsequent kidney transplantation (n=3). Conclusion: Most patients presented with severe infantile forms of PH. Patients with two truncating mutations displayed more severe phenotypes than those of patients with one truncating mutation. Sequential liver and kidney transplantation was adopted for PH1 patients presenting with ESRD. A larger nation-wide multicenter study is needed to confirm the genotype-phenotype correlations and outcomes of organ transplantation.

Yvrk 유전자를 발현하는 수산 분해 대장균 제작

정병창,김현회,박용현 대한비뇨의학회 2009 Investigative and Clinical Urology Vol.50 No.10

Purpose: Recently, the whole DNA sequence of Bacillus subtilis (B. subtilis) was identified, revealing the existence of the YvrK gene encoding a 43 kD oxalate decarboxylase (OXDC), which degrades oxalate by a simple pathway. The objective of this study was to develop recombinant Escherichia coli (E. coli) expressing the Yvrk gene from B. subtilis. Materials and Methods: After the extraction of total DNA from B. subtilis, the YvrK gene was cloned by polymerase chain reaction. The cloned DNA encoding OXDC was inserted into the pBAD/gIII-A vector, downstream of the L-arabinose promotor. The plasmid vector was transformed into TOP 10 E. coli, and the transformants were selected with ampicillin. The recombinant E. coli, named pBy, was then analyzed by DNA sequencing and Western blot. To evaluate the oxalate-degrading function of pBy, pBy was cultured in LB broth containing oxalate, and then the amount of oxalate in the medium was assessed. The oxalate-degrading activity of homogenates of pBy was evaluated. Results: DNA sequencing showed the successful transformation of the YvrK gene into TOP 10 E. coli. Western blot analyses showed that pBy expressed OXDC. pBy removed oxalate during the overnight culture in oxalate-containing LB broth, and the homogenate of pBy degraded 90% of oxalate under acidic conditions. Conclusions: A recombinant E. coli expressing the YvrK gene was successfully produced. The bacteria showed potent oxalate-degrading activity. The results of this study will provide a solution to the treatment of calcium oxalate stones and hyperoxaluria, for which there are few medical treatment modalities. Purpose: Recently, the whole DNA sequence of Bacillus subtilis (B. subtilis) was identified, revealing the existence of the YvrK gene encoding a 43 kD oxalate decarboxylase (OXDC), which degrades oxalate by a simple pathway. The objective of this study was to develop recombinant Escherichia coli (E. coli) expressing the Yvrk gene from B. subtilis. Materials and Methods: After the extraction of total DNA from B. subtilis, the YvrK gene was cloned by polymerase chain reaction. The cloned DNA encoding OXDC was inserted into the pBAD/gIII-A vector, downstream of the L-arabinose promotor. The plasmid vector was transformed into TOP 10 E. coli, and the transformants were selected with ampicillin. The recombinant E. coli, named pBy, was then analyzed by DNA sequencing and Western blot. To evaluate the oxalate-degrading function of pBy, pBy was cultured in LB broth containing oxalate, and then the amount of oxalate in the medium was assessed. The oxalate-degrading activity of homogenates of pBy was evaluated. Results: DNA sequencing showed the successful transformation of the YvrK gene into TOP 10 E. coli. Western blot analyses showed that pBy expressed OXDC. pBy removed oxalate during the overnight culture in oxalate-containing LB broth, and the homogenate of pBy degraded 90% of oxalate under acidic conditions. Conclusions: A recombinant E. coli expressing the YvrK gene was successfully produced. The bacteria showed potent oxalate-degrading activity. The results of this study will provide a solution to the treatment of calcium oxalate stones and hyperoxaluria, for which there are few medical treatment modalities.

Primary Hyperoxaluria in Korean Pediatric Patients

Choe, Yunsoo,Lee, Jiwon M.,Kim, Ji Hyun,Cho, Myung Hyun,Kim, Seong Heon,Lee, Joo Hoon,Park, Young Seo,Kang, Hee Gyung,Ha, Il Soo,Cheong, Hae Il Korean Society of Pediatric Nephrology 2019 Childhood kidney diseases Vol.23 No.2

Background: Primary hyperoxaluria (PH), a rare inborn error of glyoxylate meta bolism causing overproduction of oxalate, is classified into three genetic subgroups: type 1-3 (PH1-PH3) caused by AGXT, GRHPR, and HOGA1 gene mutations, respectively. We performed a retrospective case series study of Korean pediatric patients with PH. Methods: In total, 11 unrelated pediatric patients were recruited and their phenotypes and genotypes were analyzed by a retrospective review of their medical records. Results: Mutational analyses revealed biallelic AGXT mutations (PH1) in nine patients and a single heterozygous GRHPR and HOGA1 mutation in one patient each. The c.33dupC was the most common AGXT mutation with an allelic frequency of 44%. The median age of onset was 3 months (range, 2 months-3 years), and eight patients with PH1 presented with end stage renal disease (ESRD). Patients with two truncating mutations showed an earlier age of onset and more frequent retinal involvement than patients with one truncating mutation. Among eight PH1 patients presenting with ESRD, five patients were treated with intensive dialysis followed by liver transplantation (n=5) with/without subsequent kidney transplantation (n=3). Conclusion: Most patients presented with severe infantile forms of PH. Patients with two truncating mutations displayed more severe phenotypes than those of patients with one truncating mutation. Sequential liver and kidney transplantation was adopted for PH1 patients presenting with ESRD. A larger nation-wide multicenter study is needed to confirm the genotype-phenotype correlations and outcomes of organ transplantation.

만성 신부전증으로 내원한 원발성 과옥살산뇨증 (Primary Hyperoxaluria)

이한규 ( Han Kyu Lee ),권오경 ( O Kyong Kwon ),이영모,나기량 ( Ki Ryang Na ),서광선 ( Kwang Sun Suh ),김숙자 ( Sook Za Kim ),이강욱 ( Kang Wook Lee ),신영태 ( Young Tai Shin ) 대한신장학회 2005 Kidney Research and Clinical Practice Vol.24 No.6

The Clinical Features and Prognosis of Nephrocalcinosis in Preterm Neonates : A Single Center Study in Korea

이현주,심소연,박은애,조수진 대한신생아학회 2016 Neonatal medicine Vol.23 No.3

Purpose: Nephrocalcinosis (NC) is frequently observed in premature infants. Small-scale studies have suggested that NC adversely affects renal function; however, the etiologic factors are still unclear. This prospective observational study aimed to iden- tify the factors that influence the development of NC, through urine analysis. Methods: In total, 99 preterm infants (gestational age <34 weeks) diagnosed with NC in the neonatal intensive care unit (NICU) from October 2010 to March 2014 were evaluated. Data regarding perinatal characteristics, respiratory support, total parente- ral nutrition (TPN), and use of nephrotoxic drugs were analyzed. After an ultrasono- graphic diagnosis of NC, the infants were subjected to biweekly urine tests along with ultrasonographic follow-ups until the resolution of NC, in the outpatient department. Results: NC was diagnosed in 23% (99/432) of the preterm infants admitted to the NICU. Their median gestational age and birth weight were 28+3 (range:23+5-35+2) weeks and 1,120 (range: 560-1,950) g, respectively. NC was diagnosed an average of 26.4±2.8 (range: 2-82) days after birth, and the corrected gestational age at that time was 32.4± 2.0 weeks. Preterm infants with NC had hyperoxaluria (oxalate/Cr=4.1 [oxalate/Cr< 0.3]), and low urinary citrate levels (citrate/Cr=0.03 [citrate/Cr>0.51]). The follow-up rate was 52% (27/52) and symptoms in none of the infants had progressed to nephro- lithiasis. In the infants that were followed up, NC was resolved at a mean age of 7.7 (range: 2-32) months. Conclusion: Our results suggest that hyperoxaluria is a significant risk factor for the development of NC.

Effect of curcumin in the prevention of experimentally induced nephrolithiasis in rats by ethylene glycol and Vitamin D3

Chintan N Gandhi,R Balaraman 경희대학교 융합한의과학연구소 2009 Oriental Pharmacy and Experimental Medicine Vol.9 No.3

Curcumin (CMN) is known to have beneficial role in anorexia, coryza, cough, diabetic wounds, and hepatic disorders apart from its inherent antioxidant effects. Therefore, the present study was aimed to evaluate antioxidant effect of CMN in prevention of nephrolithiasis in rats-induced by ethylene glycol (EG) and Vitamin D3 (Vit. D3). Male Wistar rats (175 - 200 g) were randomized in groups like control, EG + Vit. D3 induced nephrolithiatiatic rats, CMN treated rats, CMN + EG + Vit. D3 treated rats, Vit. E + EG + Vit. D3 treated rats. Urine was collected weekly throughout the experimental protocol and estimated for calcium oxalate (CaO) count. After completion of experimental protocol serum was estimated for blood urea nitrogen and creatinine. Both the kidneys were excised and used to evaluate levels of biomarkers of oxidative stress and calcium oxalate crystal deposition by histopathological studies. Administration of EG and Vit. D3 to rats resulted in increased oxidative stress, hyperoxaluria and renal deposition of CaO crystals. Supplementation with CMN improves kidney function, reduces elevated oxidative stress, urinary oxalate level and renal deposition of CaO which shows its protective action in nephrolithiasis. The increased deposition of stone in the kidney and stone forming constituents of nephrolithiatic rats were effectively lowered by treatment of CMN. Curcumin (CMN) is known to have beneficial role in anorexia, coryza, cough, diabetic wounds, and hepatic disorders apart from its inherent antioxidant effects. Therefore, the present study was aimed to evaluate antioxidant effect of CMN in prevention of nephrolithiasis in rats-induced by ethylene glycol (EG) and Vitamin D3 (Vit. D3). Male Wistar rats (175 - 200 g) were randomized in groups like control, EG + Vit. D3 induced nephrolithiatiatic rats, CMN treated rats, CMN + EG + Vit. D3 treated rats, Vit. E + EG + Vit. D3 treated rats. Urine was collected weekly throughout the experimental protocol and estimated for calcium oxalate (CaO) count. After completion of experimental protocol serum was estimated for blood urea nitrogen and creatinine. Both the kidneys were excised and used to evaluate levels of biomarkers of oxidative stress and calcium oxalate crystal deposition by histopathological studies. Administration of EG and Vit. D3 to rats resulted in increased oxidative stress, hyperoxaluria and renal deposition of CaO crystals. Supplementation with CMN improves kidney function, reduces elevated oxidative stress, urinary oxalate level and renal deposition of CaO which shows its protective action in nephrolithiasis. The increased deposition of stone in the kidney and stone forming constituents of nephrolithiatic rats were effectively lowered by treatment of CMN.