Dataset Information

4-hydroxyglutamate is a biomarker for primary hyperoxaluria type 3.

ABSTRACT: Primary hyperoxaluria type 3 (PH3) is a recently identified inborn error of 4-hydroxyproline metabolism causing kidney stone disease. Diagnosis to date has relied on mutation detection. The excretion of 4-hydroxyglutamate (4OHGlu) was investigated in controls and a cohort of nine patients with PH3 and their parents using flow injection tandem mass spectrometry. 4OHGlu was stable in acidified urine samples and was not influenced by diet. Its measurement was readily incorporated into an existing multi-analyte panel for comprehensive screening for inborn errors of metabolism. There was a steady decline with age in 4OHGlu levels, expressed as ?mol/mmol of creatinine, in controls. Levels in patients with PH3 ranged from 6.5 to 98 ?mol/mmol of creatinine and were all significantly increased when compared to age-matched controls (<4.2). Levels in eight parents (obligatory carriers of the corresponding mutation) were moderately, but significantly increased, ranging from 0.6 to 2.5 (age-matched controls <1.4, p?=?0.03). Urine 4OHGlu screening was used to prospectively diagnose PH3 in an 18-month-old boy with calcium oxalate kidney stone disease associated with hyperoxaluria. 4OHGlu was also increased in a stored newborn screening dried blood spot sample from this child (37 ?mol/L, controls <2.53). 4OHGlu testing provides a robust and high-throughput biochemical screen for PH3.

SUBMITTER: Pitt JJ

PROVIDER: S-EPMC4270872 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

4-hydroxyglutamate is a biomarker for primary hyperoxaluria type 3.

Pitt James J JJ Willis Frank F Tzanakos Nicholas N Belostotsky Ruth R Frishberg Yaacov Y

JIMD reports 20140222

Primary hyperoxaluria type 3 (PH3) is a recently identified inborn error of 4-hydroxyproline metabolism causing kidney stone disease. Diagnosis to date has relied on mutation detection. The excretion of 4-hydroxyglutamate (4OHGlu) was investigated in controls and a cohort of nine patients with PH3 and their parents using flow injection tandem mass spectrometry. 4OHGlu was stable in acidified urine samples and was not influenced by diet. Its measurement was readily incorporated into an existing m ...[more]

PMID: 24563386

Similar Datasets

Project description:Primary hyperoxalurias are rare inborn errors of metabolism resulting in increased endogenous production of oxalate that leads to excessive urinary oxalate excretion. Diagnosis of primary hyperoxaluria type 1 (PH1) is a challenging issue and depends on diverse diagnostic tools including biochemical analysis of urine, stone analysis, renal biopsy, genetic studies and in some cases liver biopsy for enzyme assay. We characterized the clinical presentation as well as renal and extrarenal phenotypes in PH1 patients.This descriptive cohort study included patients with presumable PH1 presenting with nephrolithiasis and/or nephrocalcinosis (NC). Precise clinical characterization of renal phenotype as well as systemic involvement is reported. AGXT mutational analysis was performed to confirm the diagnosis of PH1.The study cohort included 26 patients with presumable PH1 with male to female ratio of 1.4:1. The median age at time of diagnosis was 6 years, nevertheless the median age at initial symptoms was 3 years. Thirteen patients (50%) were diagnosed before the age of 5 years. Two patients had no symptoms and were diagnosed while screening siblings of index patients. Seventeen patients (65.4%) had reached end-stage renal disease (ESRD): 6/17 (35.3%) during infancy, 4/17 (23.5%) in early childhood and 7/17 (41.29%) in late childhood. Two patients (7.7%) had clinically manifest extra renal (retina, heart, bone, soft tissue) involvement. Mutational analysis of AGXT gene confirmed the diagnosis of PH1 in 15 out of 19 patients (79%) where analysis had been performed. Fifty percent of patients with maintained renal functions had projected 10 years renal survival.PH1 is a heterogeneous disease with wide spectrum of clinical, imaging and functional presentation. More than two-thirds of patients presented prior to the age of 5 years; half of them with the stormy course of infantile PH1. ESRD was the commonest presenting manifestation in two-thirds of our cohort.

Dataset Information

4-hydroxyglutamate is a biomarker for primary hyperoxaluria type 3.

Publications

4-hydroxyglutamate is a biomarker for primary hyperoxaluria type 3.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets