Quebec neonatal mass urinary screening programme: From micromolecules to macromolecules

Auray‐Blais, Christiane; Cyr, Denis; Drouin, Régen

doi:10.1007/s10545-007-0607-x

Cited by 64 publications

(41 citation statements)

References 9 publications

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“…Seven families, including French-Canadians (pedigrees 1-3) and Australians (pedigrees 4-7), each containing an index case initially identified from newborn urinary screening programs for IG (33,34), were recruited for this study (Figure 1). Most probands who had IG diagnosed as infants (subjects 1.3, 1.4, 2.3, 2.4, 3.3, 4.4, and 7.6) were reconfirmed in this study, whereas subjects 5.3 and 6.4 persisted with only HG.…”

Section: Resultsmentioning

confidence: 99%

Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters

Bröer¹,

Bailey²,

Kowalczuk³

et al. 2008

J. Clin. Invest.

105

104

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Iminoglycinuria (IG)is an autosomal recessive abnormality of renal transport of glycine and the imino acids proline and hydroxyproline, but the specific genetic defect(s) have not been determined. Similarly, although the related disorder hyperglycinuria (HG) without iminoaciduria has been attributed to heterozygosity of a putative defective glycine, proline, and hydroxyproline transporter, confirming the underlying genetic defect(s) has been difficult. Here we applied a candidate gene sequencing approach in 7 families first identified through newborn IG screening programs. Both inheritance and functional studies identified the gene encoding the proton amino acid transporter SLC36A2 (PAT2) as the major gene responsible for IG in these families, and its inheritance was consistent with a classical semidominant pattern in which 2 inherited nonfunctional alleles conferred the IG phenotype, while 1 nonfunctional allele was sufficient to confer the HG phenotype. Mutations in SLC36A2 that retained residual transport activity resulted in the IG phenotype when combined with mutations in the gene encoding the imino acid transporter SLC6A20 (IMINO). Additional mutations were identified in the genes encoding the putative glycine transporter SLC6A18 (XT2) and the neutral amino acid transporter SLC6A19 (B 0 AT1) in families with either IG or HG, suggesting that mutations in the genes encoding these transporters may also contribute to these phenotypes. In summary, although recognized as apparently simple Mendelian disorders, IG and HG exhibit complex molecular explanations depending on a major gene and accompanying modifier genes.

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Section: Resultsmentioning

confidence: 99%

Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters

Bröer¹,

Bailey²,

Kowalczuk³

et al. 2008

J. Clin. Invest.

105

104

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show abstract

“…He came to clinical attention through population urine-based newborn screening. In the Quebec Neonatal Urine Screening Programme (Auray-Blais et al 2007), an infant's urine sample is collected on filter paper and submitted by parents. Screening is performed on eluted GA glutaric acid, 3HGA 3-hydroxyglutaric acid, HMG 3-hydroxy-3-methylglutaric acid, Ket ketones, Dic dicarboxylic acids, Gut acids of probable intestinal origin (including methylmalonic, 3-hydroxypropionic, 4-hydroxyphenyllactic), SNS other acids considered secondary or nonspecific, NA not analysed (specimen not available), NC could not be calculated Concentrations of organic acids other than GA and 3HGA are summarised as follows: À denotes within reference range; + denotes 1Â-3Â reference limit; ++ denotes 3Â-10Â reference limit; +++ denotes >10Â reference limit a All organic acids are expressed in mmol/mol creatinine.…”

Section: Patientmentioning

confidence: 99%

Glutaric Aciduria Type 3: Three Unrelated Canadian Cases, with Different Routes of Ascertainment

et al. 2017

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Glutaric aciduria type 3 (GA3) is associated with decreased conversion of free glutaric acid to glutaryl-coA, reflecting deficiency of succinate-hydroxymethylglutarate coA-transferase, caused by variants in the SUGCT (C7orf10) gene. GA3 remains less well known, characterised and understood than glutaric aciduria types 1 and 2. It is generally considered a likely "non-disease," but this is based on limited supporting information, with only nine individuals with GA3 described in the literature. Clinicians encountering a patient with GA3 therefore still face a dilemma of whether or not this should be dismissed as irrelevant.We have identified three unrelated Canadian patients with GA3. Two came to clinical attention because of symptoms, while the third was identified by a population urine-based newborn screening programme and has so far remained asymptomatic. We describe the clinical histories, biochemical characterisation and genotypes of these individuals. Examination of allele frequencies underlines the fact that GA3 is underdiagnosed. While one probable factor is that some GA3 patients remain asymptomatic, we highlight other plausible reasons whereby this diagnosis might be overlooked.Gastrointestinal disturbances were previously reported in some GA3 patients. In one of our patients, severe episodes of cyclic vomiting were the major problem. A trial of antibiotic treatment, to minimise bacterial GA production, was followed by significant clinical improvement.At present, there is insufficient evidence to define any specific clinical phenotype as attributable to GA3. However, we consider that it would be premature to assume that this condition is completely benign in all individuals at all times.

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“…Can be collected at any age but routinely collected by parents at 21 days of age in Quebec following an instruction sheet [8].…”

Section: Cord Blood Dbs Collected At a Few Days Of Agementioning

confidence: 99%

“…Quebec moved the age of collection from 5 days age to 14 days of age and finally to 21 days to minimise the risk of false negatives and false positives [8]. Late onset urea cycle defects thereby identified.…”

Section: Cord Blood Dbs Collected At a Few Days Of Agementioning

confidence: 99%

Suitable Specimen Types for Newborn Biochemical Screening-A Summary

Hall¹

2017

IJNS

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Newborn biochemical screening has been in place in many countries for over fifty years initially testing dried skin puncture whole blood spotted on collection paper (DBS) or urine for phenylalanine or phenylketones to identify phenylketonuria. Countries wishing to commence newborn screening need to consider which type of specimen will provide a satisfactory specimen and matrix for testing for disorders relevant to their population, is acceptable to parents and can be readily transported to the analytical or laboratory facility without significant degradation. Whilst DBSs have largely become the specimen of choice they may not be applicable to all cultures and infrastructures. The majority of disorders appropriate to be identified in the newborn period can be detected in DBSs taken shortly after birth. Some are also detectable in cord blood or urine, some are not. Most disorders have an ideal and often different time window of age for identification in relation to treatment for optimum outcome. When embarking on newborn screening for the first time or in expanding what is already in place, it is important that the disorders considered are evaluated against the Wilson and Jungner criteria for population screening. A brief overview of specimen types including urine, cord blood and DBSs with some of their advantages and limitations is provided in this review to assist in decision-making.

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Quebec neonatal mass urinary screening programme: From micromolecules to macromolecules

Cited by 64 publications

References 9 publications

Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters

Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters

Glutaric Aciduria Type 3: Three Unrelated Canadian Cases, with Different Routes of Ascertainment

Suitable Specimen Types for Newborn Biochemical Screening-A Summary

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