scholarly journals Outcomes of early repeat sweat testing in infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID)

2021 ◽  
Author(s):  
vito terlizzi ◽  
Laura Claut ◽  
Carla Colombo ◽  
Antonella Tosco ◽  
Alice Castaldo ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Definitive Diagnosis ◽  
First Year ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Sweat Chloride ◽  
Sweat Testing ◽  
Cf Transmembrane Conductance Regulator ◽  
First Year Of Life

Background: Reaching early and definitive diagnosis in infants with cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID) is a priority of all CF newborn screening programs. Currently, sweat testing is the gold standard for CF diagnosis or exclusion. We assessed outcomes in a cohort of Italian CRMS/CFSPID infants who underwent repeat sweat testing in the first year of life. Methods: This multicentre, prospective study analysed clinical data and outcomes in CRMS/CFSPID infants born between September 1, 2018 and December 31, 2019, and followed until June 30, 2020. All subjects underwent CF transmembrane conductance regulator (CFTR) gene sequencing and the search for CFTR macrodeletions/macroduplications, and repeat sweat testing in the first year of life. Results: Fifty subjects (median age at end of follow-up, 16 months [range, 7–21 months]) were enrolled. Forty-one (82%) had the first sweat chloride in the intermediate range. During follow up, 150 sweat tests were performed (range, 1–7/infant). After a median follow-up of 8.5 months (range 1–16.2 months), 11 (22%) subjects were definitively diagnosed as follows: CF (n=2 [4%]) at 2 and 5 months, respectively; healthy carrier (n=8 [16%]), at a median age of 4 months (range 2–8 months); and healthy (n=1 [2%]) at 2 months of age. Inconclusive diagnosis remained in 39 (78%) infants. Conclusions: Early repeat sweat testing in the first year of life can shorten the time to definitive diagnosis in screening positive subjects with initial sweat chloride levels in the intermediate range.

scholarly journals Recurrent Cough and Expectoration for 10 Years: A Case Report

2019 ◽  
Vol 6 ◽  
pp. 2333794X1983372
Author(s):  
Ting Huang ◽  
Caihong Li ◽  
Daishun Liu
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Mutation ◽  
Definitive Diagnosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Children's Hospital ◽  
Children’S Hospital ◽  
Sweat Testing ◽  
Tract Infections ◽  
Cystic Fibrosis Transmembrane

Rationale. Most cases of cystic fibrosis occur in Europe, with only a few occurring in Asia. Pulmonary cystic fibrosis is not a rare disease, but in children it is a potentially life-threatening condition. Children suffering from pulmonary cystic fibrosis rarely survive to adulthood, and responses to treatment are generally poor. The most common cause of cystic fibrosis is a genetic mutation on chromosome 7. Patient concerns. A 15-year-old boy with healthy parents suffered from a recurrent cough and expectoration for nearly 10 years. Six years previously, a definitive diagnosis of pulmonary cystic fibrosis and hepatic cirrhosis was made at the Beijing Children’s Hospital. The first occurrence of hematemesis occurred 1 year ago. The main symptoms, which caused this period of hospitalization, were cough, expectoration, and hematemesis. Diagnoses. The underlying cause was finally determined to be the cystic fibrosis transmembrane conductance regulator gene (p.G970D). After genetic and sweat testing performed at the Beijing Children’s Hospital in 2012, a definitive diagnosis of cystic fibrosis was made. Interventions. The patient was administered hemostatic treatment, antibiotics, and cough relief and sputum reduction therapy. Outcomes. The patient’s condition rapidly improved and continued to remain stable, though future relapse is possible following respiratory tract infections. Lessons. This case indicates that in the case of any child that presents a recurrent cryptogenic cough and expectoration, whether accompanied by hematemesis or not, pulmonary cystic fibrosis should be considered. In order to determine underlying causes and prepare for cystic fibrosis transmembrane conductance regulator modulator therapy, genetic and sweat testing are recommended to be conducted if available.

Outcomes of Cystic Fibrosis Screening–Positive Infants With Inconclusive Diagnosis at School Age

PEDIATRICS ◽  
2021 ◽  
Author(s):  
Tanja Gonska ◽  
Katherine Keenan ◽  
Jacky Au ◽  
Annie Dupuis ◽  
Mark A. Chilvers ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Concentration ◽  
Predictive Biomarkers ◽  
School Age ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Sweat Chloride ◽  
Sweat Testing ◽  
Prospective Longitudinal ◽  
Cystic Fibrosis Transmembrane

BACKGROUND AND OBJECTIVES Cystic fibrosis (CF) screen–positive infants with an inconclusive diagnosis (CFSPID) are infants in whom sweat testing and genetic analysis does not resolve a CF diagnosis. Lack of knowledge about the health outcome of these children who require clinical follow-up challenges effective consultation. Early predictive biomarkers to delineate the CF risk would allow a more targeted approach to these children. METHODS Prospective, longitudinal, multicenter, Canada-wide cohort study of CF positive–screened newborns with 1 to 2 cystic fibrosis transmembrane conductance regulator gene variants, of which at least 1 is not known to be CF-causing and/or a sweat chloride between 30 and 59 mmol/L. These were monitored for conversion to a CF diagnosis, pulmonary, and nutritional outcomes. RESULTS The mean observation period was 7.7 (95% confidence interval 7.1 to 8.4) years. A CF diagnosis was established for 24 of the 115 children with CFSPID (21%) either because of reinterpretation of the cystic fibrosis transmembrane conductance regulator genotype or because of increase in sweat chloride concentration ≥60 mmol/L. An initial sweat chloride of ≥40 mmol/l predicted conversion to CF on the basis of sweat testing. The 91 remaining children with CFSPID were pancreatic sufficient and showed normal growth until school age. Pulmonary function as well as lung clearance index in a subgroup of children with CFSPID were similar to that of healthy controls. CONCLUSIONS Children with CFSPID have good nutritional and pulmonary outcomes at school age, but rates of reclassifying the diagnosis are high. The initial sweat chloride test can be used as a biomarker to predict the risk for CF in CFSPID.

Muenke syndrome: long-term outcome of a syndrome-specific treatment protocol

2019 ◽  
Vol 24 (4) ◽  
pp. 415-422 ◽  
Author(s):  
Bianca K. den Ottelander ◽  
Robbin de Goederen ◽  
Marie-Lise C. van Veelen ◽  
Stephanie D. C. van de Beeten ◽  
Maarten H. Lequin ◽  
...  
Keyword(s):  
Treatment Protocol ◽  
First Year ◽  
Ventricular Size ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Skull Growth ◽  
Muenke Syndrome ◽  
First Year Of Life

OBJECTIVEThe authors evaluated the long-term outcome of their treatment protocol for Muenke syndrome, which includes a single craniofacial procedure.METHODSThis was a prospective observational cohort study of Muenke syndrome patients who underwent surgery for craniosynostosis within the first year of life. Symptoms and determinants of intracranial hypertension were evaluated by longitudinal monitoring of the presence of papilledema (fundoscopy), obstructive sleep apnea (OSA; with polysomnography), cerebellar tonsillar herniation (MRI studies), ventricular size (MRI and CT studies), and skull growth (occipital frontal head circumference [OFC]). Other evaluated factors included hearing, speech, and ophthalmological outcomes.RESULTSThe study included 38 patients; 36 patients underwent fronto-supraorbital advancement. The median age at last follow-up was 13.2 years (range 1.3–24.4 years). Three patients had papilledema, which was related to ophthalmological disorders in 2 patients. Three patients had mild OSA. Three patients had a Chiari I malformation, and tonsillar descent < 5 mm was present in 6 patients. Tonsillar position was unrelated to papilledema, ventricular size, or restricted skull growth. Ten patients had ventriculomegaly, and the OFC growth curve deflected in 3 patients. Twenty-two patients had hearing loss. Refraction anomalies were diagnosed in 14/15 patients measured at ≥ 8 years of age.CONCLUSIONSPatients with Muenke syndrome treated with a single fronto-supraorbital advancement in their first year of life rarely develop signs of intracranial hypertension, in accordance with the very low prevalence of its causative factors (OSA, hydrocephalus, and restricted skull growth). This illustrates that there is no need for a routine second craniofacial procedure. Patient follow-up should focus on visual assessment and speech and hearing outcomes.

Liquid secretion inhibitors reduce mucociliary transport in glandular airways

2002 ◽  
Vol 283 (2) ◽  
pp. L329-L335 ◽  
Author(s):  
Stephen T. Ballard ◽  
Laura Trout ◽  
Anil Mehta ◽  
Sarah K. Inglis
Keyword(s):  
Beat Frequency ◽  
Anion Channel ◽  
Ciliary Beat Frequency ◽  
Mucociliary Transport ◽  
Transmembrane Conductance Regulator ◽  
Inhibitory Effects ◽  
Transmembrane Conductance ◽  
Regulator Protein ◽  
Liquid Absorption ◽  
Cf Transmembrane Conductance Regulator

Because of its possible importance in cystic fibrosis (CF) pulmonary pathogenesis, the effect of anion and liquid secretion inhibitors on airway mucociliary transport was examined. When excised porcine tracheas were treated with ACh to induce gland liquid secretion, the rate of mucociliary transport was increased nearly threefold from 2.5 ± 0.5 to 6.8 ± 0.8 mm/min. Pretreatment with both bumetanide and dimethylamiloride (DMA), to respectively inhibit Cl− and HCO[Formula: see text]secretion, significantly reduced mucociliary transport in the presence of ACh by 92%. Pretreatment with the anion channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid similarly reduced mucociliary transport in ACh-treated airways by 97%. These agents did not, however, reduce ciliary beat frequency. Luminal application of benzamil to block liquid absorption significantly attenuated the inhibitory effects of bumetanide and DMA on mucociliary transport. We conclude that anion and liquid secretion is essential for normal mucociliary transport in glandular airways. Because the CF transmembrane conductance regulator protein likely mediates Cl−, HCO[Formula: see text], and liquid secretion in normal glands, we speculate that impairment of gland liquid secretion significantly contributes to defective mucociliary transport in CF.

Abnormal Shoulder Girdle Muscle Tone in Premature Infants During Their First 18 Months of Life

PEDIATRICS ◽  
1986 ◽  
Vol 77 (5) ◽  
pp. 664-669
Author(s):  
Michael K. Georgieff ◽  
Judy C. Bernbaum
Keyword(s):  
Premature Infants ◽  
Motor Development ◽  
Muscle Tone ◽  
Birth Asphyxia ◽  
Shoulder Girdle ◽  
First Year ◽  
First Year Of Life ◽  
Girdle Muscle ◽  
Shoulder Girdle Muscle

To document the incidence of and neonatal factors associated with abnormal shoulder girdle muscle tone in premature infants at follow-up, we studied 125 consecutively admitted infants weighing &lt; 1,750 g treated in The Children's Hospital of Philadelphia intensive care nursery and subsequently seen in the Neonatal Follow-up Program up to 18 months of age. Fifty-seven infants (46%) displayed abnormal shoulder girdle muscle tone which presented clinically as scapular retractions. These infants had significantly lower birth weights (P &lt; .001) and gestational age (P &lt; .001) as well as a higher incidence of acute and chronic pulmonary disease (P &lt; 0.01) and CNS insults (P &lt; .05) when compared with infants without scapular retractions. The 57 infants with scapular retractions were further divided into two groups: 42 infants (74%) in whom scapular retractions were associated with generalized mild hypertonicity and 15 infants (26%) in whom scapular retractions compensated for trunk and neck hypotonicity. The infants with scapular retractions and hypotonicity had a significantly higher incidence of neonatal neurologic morbidity including seizures, major resuscitations, and birth asphyxia (P &lt; .01) when compared with the infants with scapular retractions and hypertonicity. Shoulder girdle tone abnormalities in the first year of life inhibit crawling, sitting, and object manipulation and, therefore, may manifest as delays in motor development. Identification of infants with significant neonatal risk factors for tone abnormalities is important to allow for earlier therapeutic intervention.

scholarly journals Safety of potential breast milk exposure to IFN-β or glatiramer acetate

2020 ◽  
Vol 7 (4) ◽  
pp. e757
Author(s):  
Andrea Ines Ciplea ◽  
Annette Langer-Gould ◽  
Anna Stahl ◽  
Sandra Thiel ◽  
Annette Queisser-Wahrendorf ◽  
...  
Keyword(s):  
Breast Milk ◽  
Glatiramer Acetate ◽  
Growth Curves ◽  
Antibiotic Use ◽  
Physical Growth ◽  
First Year ◽  
Motor Delay ◽  
Infant Outcomes ◽  
First Year Of Life

ObjectiveTo determine whether potential breast milk exposure to interferon-beta (IFN-β) or glatiramer acetate (GA) is safe for the infant.MethodsWe identified 74 infants born to 69 women with MS who breastfed under IFN-β (n = 39), GA (n = 34), or both (n = 1). Women had been enrolled into the German Multiple Sclerosis and Pregnancy Registry during pregnancy. Data were obtained from standardized, telephone-administered questionnaires completed by the mother during pregnancy and at 1, 3, 6, and 12 months postpartum and the infant's take-home medical record.ResultsThe median duration of exposed breastfeeding was 8.5 months (wide interquartile range: 4.9–12.7 months). Physical growth curves during the first year of life were consistent with national, sex-specific growth curves. Median body measurements were consistent with national medians. Most children (n = 71, 96%) had normal motor and language development. Gross motor delay was reported in 3 children, of whom 1 remained delayed at last follow-up (3.9 years old) and 2 were normal by 0.9 and 4.1 years old. The proportion of children hospitalized at least once (girls n = 2, 7%, and boys n = 6, 14%) and the proportion of children with at least one episode of systemic antibiotic use during the first year of life (girls n = 7, 23%, and boys n = 8, 18%) are consistent with national averages.ConclusionPotential breast milk exposure to IFN-β or GA did not increase the risk of common adverse infant outcomes in the first year of life. Taken together with the benefits of breastfeeding and low biological plausibility of risk, women with MS who wish to resume IFN-β or GA postpartum can be encouraged to breastfeed.

scholarly journals International Approaches to Management of CFTR-Related Metabolic Syndrome/Cystic Fibrosis Screen Positive, Inconclusive Diagnosis

2022 ◽  
Vol 8 (1) ◽  
pp. 5
Author(s):  
Jane Chudleigh ◽  
Jürg Barben ◽  
Clement L. Ren ◽  
Kevin W. Southern
Keyword(s):  
Metabolic Syndrome ◽  
Cystic Fibrosis ◽  
Health Professionals ◽  
Online Survey ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Online Questionnaire ◽  
The Us ◽  
The Uk ◽  
Cystic Fibrosis Transmembrane

The main aim of the present study was to explore health professionals’ reported experiences and approaches to managing children who receive a designation of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive inconclusive diagnosis following a positive NBS result for cystic fibrosis. An online questionnaire was distributed via Qualtrics Survey Software and circulated to a purposive, international sample of health professionals involved in managing children with this designation. In total, 101 clinicians completed the online survey: 39 from the US, six from Canada, and 56 from Europe (including the UK). Results indicated that while respondents reported minor deviations in practice, they were cognizant of recommendations in the updated guidance and for the most part, attempted to implement these into practice consistently internationally. Where variation was reported, the purpose of this appeared to be to enable clinicians to respond to either clinical assessments or parental anxiety in order to improve outcomes for the child and family. Further research is needed to determine if these findings are reflective of both a wider audience of clinicians and actual (rather than reported) practice.

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