Cystic Fibrosis Newborn Screening: Distribution of Blood Immunoreactive Trypsinogen Concentrations in Hypertrypsinemic Neonates

Paracchini, Valentina; Seia, Manuela; Raimondi, Sara; Costantino, Lucy; Capasso, P.; Porcaro, Luigi; Colombo, Carla; Coviello, Domenico; Mariani, T.; Manzoni, E; Sangiovanni, M.; Corbetta, Carlo

doi:10.1007/8904_2011_55

Cited by 21 publications

(10 citation statements)

References 21 publications

(20 reference statements)

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“…The results showed that among a total of 717,172 newborns screened, 7354 newborns were found positive to NBS. After the second screening by sweat test, 7234 newborns (98.4%: false positive) were negative or not confirmed, while 120 newborns (1.6%) were confirmed as a patient with CF [61]. These results support our hypothesis that using the LC–MS/MS method to measure GAGs can be applied to NBS for MPS.…”

Section: Update Of Lc–ms/ms Methods With Enzyme Digestionsupporting

confidence: 59%

Newborn screening and diagnosis of mucopolysaccharidoses

Tomatsu

Fujii

Fukushi

et al. 2013

Molecular Genetics and Metabolism

136

124

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Mucopolysaccharidoses (MPS) are caused by deficiency of lysosomal enzyme activities needed to degrade glycosaminoglycans (GAGs), which are long unbranched polysaccharides consisting of repeating disaccharides. GAGs include: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and hyaluronan. Their catabolism may be blocked singly or in combination depending on the specific enzyme deficiency. There are 11 known enzyme deficiencies, resulting in seven distinct forms of MPS with a collective incidence of higher than 1 in 25,000 live births. Accumulation of undegraded metabolites in lysosomes gives rise to distinct clinical syndromes. Generally, the clinical conditions progress if untreated, leading to developmental delay, systemic skeletal deformities, and early death. MPS disorders are potentially treatable with enzyme replacement therapy or hematopoietic stem cell transplantation. For maximum benefit of available therapies, early detection and intervention are critical. We recently developed a novel high-throughput multiplex method to assay DS, HS, and KS simultaneously in blood samples by using high performance liquid chromatography/tandem mass spectrometry for MPS. The overall performance metrics of HS and DS values on MPS I, II, and VII patients vs. healthy controls at newborns were as follows using a given set of cut-off values: sensitivity, 100%; specificity, 98.5–99.4%; positive predictive value, 54.5–75%; false positive rate, 0.62–1.54%; and false negative rate, 0%. These findings show that the combined measurements of these three GAGs are sensitive and specific for detecting all types of MPS with acceptable false negative/positive rates. In addition, this method will also be used for monitoring therapeutic efficacy. We review the history of GAG assay and application to diagnosis for MPS.

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Section: Update Of Lc–ms/ms Methods With Enzyme Digestionsupporting

confidence: 59%

Newborn screening and diagnosis of mucopolysaccharidoses

Tomatsu

Fujii

Fukushi

et al. 2013

Molecular Genetics and Metabolism

136

124

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“…At present, there is sufficient evidence to confirm that CF is present in Palestine and that the clinical presentations of the CF patients with the different type of CFTR mutations were similar to what reported worldwide. The newborn screening program using immunoreactive trypsinogen (IRT) has been used in many countries for early detection of CF [ 25 ]. Unfortunately, this screening test is not available in Palestine.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations in a Cohort of Patients Residing in Palestine

et al. 2015

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Cystic fibrosis (CF) is an autosomal recessive inherited life-threatening disorder that causes severe damage to the lungs and the digestive system. In Palestine, mutations in the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) that contributes to the clinical presentation of CF are ill defined. A cohort of thirty three clinically diagnosed CF patients from twenty one different Palestinian families residing in the central and southern part of Palestine were incorporated in this study. Sweat chloride testing was performed using the Sweat Chek Conductivity Analyzer (ELITECH Group, France) to confirm the clinical diagnosis of CF. In addition, nucleic acid from the patients’ blood samples was extracted and the CFTR mutation profiles were assessed by direct sequencing of the CFTR 27 exons and the intron-exon boundaries. For patient’s DNA samples where no homozygous or two heterozygous CFTR mutations were identified by exon sequencing, DNA samples were tested for deletions or duplications using SALSA MLPA probemix P091-D1 CFTR assay. Sweat chloride testing confirmed the clinical diagnosis of CF in those patients. All patients had NaCl conductivity >60mmol/l. In addition, nine different CFTR mutations were identified in all 21 different families evaluated. These mutations were c.1393-1G>A, F508del, W1282X, G85E, c.313delA, N1303K, deletion exons 17a-17b-18, deletion exons 17a-17b and Q1100P. c.1393-1G>A was shown to be the most frequent occurring mutation among tested families. We have profiled the underling mutations in the CFTR gene of a cohort of 21 different families affected by CF. Unlike other studies from the Arab countries where F508del was reported to be the most common mutation, in southern/central Palestine, the c.1393-1G>A appeared to be the most common. Further studies are needed per sample size and geographic distribution to account for other possible CFTR genetic alterations and their frequencies. Genotype/phenotype assessments are also recommended and finally carrier frequency should be ascertained.

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“…Most NBS methods measure elevated substrates in organic acidemias, urea cycle disorders, and cystic fibrosis (CF). A two-tier strategy is universally used for CF [59][60][61][62].…”

Section: Introductionmentioning

confidence: 99%

Newborn screening and diagnosis of mucopolysaccharidoses

Tomatsu

Shimada

Montaño

et al. 2014

Molecular Genetics and Metabolism

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Mucopolysaccharidoses (MPS) are caused by deficiency of lysosomal enzyme activities needed to degrade glycosaminoglycans (GAGs), which are long unbranched polysaccharides consisting of repeating disaccharides. GAGs include: chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and hyaluronan. Their catabolism may be blocked singly or in combination depending on the specific enzyme deficiency. There are 11 known enzyme deficiencies, resulting in seven distinct forms of MPS with a collective incidence of higher than 1 in 25,000 live births. Accumulation of undegraded metabolites in lysosomes gives rise to distinct clinical syndromes. Generally, the clinical conditions progress if untreated, leading to developmental delay, systemic skeletal deformities, and early death. MPS disorders are potentially treatable with enzyme replacement therapy or hematopoietic stem cell transplantation. For maximum benefit of available therapies, early detection and intervention are critical. We recently developed a novel high-throughput multiplex method to assay DS, HS, and KS simultaneously in blood samples by using high performance liquid chromatography/tandem mass spectrometry for MPS. The overall performance metrics of HS and DS values on MPS I, II, and VII patients vs. healthy controls at newborns were as follows using a given set of cut-off values: sensitivity, 100%; specificity, 98.5-99.4%; positive predictive value, 54.5-75%; false positive rate, 0.62-1.54%; and false negative rate, 0%. These findings show that the combined measurements of these three GAGs are sensitive and specific for detecting all types of MPS with acceptable false

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Cystic Fibrosis Newborn Screening: Distribution of Blood Immunoreactive Trypsinogen Concentrations in Hypertrypsinemic Neonates

Abstract: The IRT screening test for the use in diagnosing newborns with CF has a high sensitivity but is not very specific resulting in a large number of screened positive infants found to have a normal sweat test.

Cited by 21 publications

References 21 publications

Newborn screening and diagnosis of mucopolysaccharidoses

Newborn screening and diagnosis of mucopolysaccharidoses

Distribution of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutations in a Cohort of Patients Residing in Palestine

Newborn screening and diagnosis of mucopolysaccharidoses

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