scholarly journals Detection of Early Onset Carnitine Palmitoyltransferase II Deficiency by Newborn Screening. Should CPT II Deficiency Be a Primary Disease Target?

2021 ◽  
Vol 7 (3) ◽  
pp. 55
Author(s):  
Rachel Mador-House ◽  
Zaiping Liu ◽  
Sarah Dyack
Keyword(s):  
Newborn Screening ◽  
Early Onset ◽  
Screening Program ◽  
Carnitine Palmitoyltransferase ◽  
Positive Case ◽  
Metabolic Decompensation ◽  
Mass Spectrometry Identification ◽  
Expanded Newborn Screening ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency

Early-onset carnitine palmitoyltransferase II deficiency (CPT II deficiency) (OMIM 600650) can result in severe outcomes, which are often fatal in the neonatal to infantile period. CPT II deficiency is a primary target in the Maritime Newborn Screening Program. We report a case of neonatal-onset CPT II deficiency identified through expanded newborn screening with tandem mass spectrometry. Identification through newborn screening led to early treatment interventions, avoidance of metabolic decompensation, and a better clinical outcome. Newborn screening for CPT II deficiency is highly sensitive and specific with no false positives identified. The only screen positive case detected identified a true positive case. This experience illustrates the importance of newborn screening for CPT II deficiency and demonstrates why reconsideration should be taken to add this disease as a primary newborn screening target.

scholarly journals Parental intentions to enroll children in a voluntary expanded newborn screening program

2016 ◽  
Vol 166 ◽  
pp. 17-24 ◽  
Author(s):  
Ryan S. Paquin ◽  
Holly L. Peay ◽  
Lisa M. Gehtland ◽  
Megan A. Lewis ◽  
Donald B. Bailey
Keyword(s):  
Newborn Screening ◽  
Screening Program ◽  
Newborn Screening Program ◽  
Expanded Newborn Screening

scholarly journals Performance of Expanded Newborn Screening in Norway Supported by Post-Analytical Bioinformatics Tools and Rapid Second-Tier DNA Analyses

2020 ◽  
Vol 6 (3) ◽  
pp. 51 ◽  
Author(s):  
Trine Tangeraas ◽  
Ingjerd Sæves ◽  
Claus Klingenberg ◽  
Jens Jørgensen ◽  
Erle Kristensen ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Screening Program ◽  
Good Health ◽  
Dried Blood Spots ◽  
Case Definitions ◽  
Inborn Errors ◽  
Disease Spectrum ◽  
Expanded Newborn Screening ◽  
Second Tier ◽  
Biochemical Testing

In 2012, the Norwegian newborn screening program (NBS) was expanded (eNBS) from screening for two diseases to that for 23 diseases (20 inborn errors of metabolism, IEMs) and again in 2018, to include a total of 25 conditions (21 IEMs). Between 1 March 2012 and 29 February 2020, 461,369 newborns were screened for 20 IEMs in addition to phenylketonuria (PKU). Excluding PKU, there were 75 true-positive (TP) (1:6151) and 107 (1:4311) false-positive IEM cases. Twenty-one percent of the TP cases were symptomatic at the time of the NBS results, but in two-thirds, the screening result directed the exact diagnosis. Eighty-two percent of the TP cases had good health outcomes, evaluated in 2020. The yearly positive predictive value was increased from 26% to 54% by the use of the Region 4 Stork post-analytical interpretive tool (R4S)/Collaborative Laboratory Integrated Reports 2.0 (CLIR), second-tier biochemical testing and genetic confirmation using DNA extracted from the original dried blood spots. The incidence of IEMs increased by 46% after eNBS was introduced, predominantly due to the finding of attenuated phenotypes. The next step is defining which newborns would truly benefit from screening at the milder end of the disease spectrum. This will require coordinated international collaboration, including proper case definitions and outcome studies.

Recurrent Myalgia since Early Infancy—Misleading Clinical Course in a Child with Carnitine Palmitoyltransferase-II Deficiency

2019 ◽  
Vol 51 (01) ◽  
pp. 053-056
Author(s):  
Maria Arélin ◽  
Stephan Zierz ◽  
Uta Ceglarek ◽  
Mitja Heinemann ◽  
Skadi Beblo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Carnitine Palmitoyltransferase ◽  
Early Infancy ◽  
Hereditary Diseases ◽  
Missense Mutations ◽  
Metabolic Myopathies ◽  
Muscle Energy ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency ◽  
Generation Sequencing

AbstractMetabolic myopathies are heterogeneous hereditary diseases affecting skeletal muscle energy supply. Symptoms usually comprise pain, cramps, hypotonia, weakness, and myoglobinuria.We present a boy with recurrent myalgia and weakness after some minutes of exercise or during febrile infections since early infancy. First laboratory workup at the age of 9 years showed no abnormalities, apart from a slightly elevated creatine kinase. After exclusion of common structural and metabolic myopathies, next generation sequencing panel (4 years after the initial diagnostic metabolic workup) revealed two potentially pathogenic missense mutations in the CPT2 gene (c.149C > A (p.P50H) and c.1459G > A (p.E487K)).Our case underscores the clinical variability of muscle carnitine palmitoyltransferase II (CPT II) deficiency and illustrates a pitfall of diagnostic algorithms for metabolic myopathies. Myalgia following exercise of a few minutes duration would have argued for a carbohydrate and against a fatty acid metabolic defect. However, CPT II deficiency is the most common disorder of muscle fatty acid metabolism and should be considered even in atypical scenarios. Analyses of plasma acyl carnitine profile during acute metabolic crises may help to unmask biochemical markers which are often overlooked in dried-blood analyses.

scholarly journals Normal FGF-21-Serum Levels in Patients with Carnitine Palmitoyltransferase II (CPT II) Deficiency

2019 ◽  
Vol 20 (6) ◽  
pp. 1400 ◽  
Author(s):  
Leila Motlagh Scholle ◽  
Diana Lehmann ◽  
Pushpa Joshi ◽  
Stephan Zierz
Keyword(s):  
Citrate Synthase ◽  
Serum Levels ◽  
Carnitine Palmitoyltransferase ◽  
Fibroblast Growth Factor 21 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Mitochondrial Fatty Acid ◽  
Significant Difference ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency

Fibroblast growth factor 21 (FGF-21) is known to be a biomarker for mitochondrial disorders. An upregulation of FGF-21 in serum and muscle of carnitine palmitoyltransferase I (CPT I) and carnitine palmitoyltransferase II (CPT II) knock-out mice has been reported. In human CPT II deficiency, enzyme activity and protein content are normal, but the enzyme is abnormally regulated by malonyl-CoA and is abnormally thermolabile. Citrate synthase (CS) activity is increased in patients with CPT II deficiency. This may indicate a compensatory response to an impaired function of CPT II. In this study, FGF-21 serum levels in patients with CPT II deficiency during attack free intervals and in healthy controls were measured by enzyme linked immunosorbent assay (ELISA). The data showed no significant difference between FGF-21 concentration in the serum of patients with CPT II deficiency and that in the healthy controls. The results of the present work support the hypothesis that in muscle CPT II deficiency, in contrast to the mouse knockout model, mitochondrial fatty acid utilization is not persistently reduced. Thus, FGF-21 does not seem to be a useful biomarker in the diagnosis of CPT II deficiency.

Identification of Four Novel Mutations in Patients with Carnitine Palmitoyltransferase II (CPT II) Deficiency

1998 ◽  
Vol 64 (4) ◽  
pp. 229-236 ◽  
Author(s):  
Bing-Zhi Yang ◽  
Jia-Huan Ding ◽  
Tracy Dewese ◽  
Diane Roe ◽  
Guocheng He ◽  
...  
Keyword(s):  
Carnitine Palmitoyltransferase ◽  
Novel Mutations ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency

Recurrent metabolic decompensation in profound carnitine palmitoyltransferase II deficiency

1993 ◽  
Vol 122 (6) ◽  
pp. 917-919 ◽  
Author(s):  
Orly N. Elpeleg ◽  
Adina Joseph ◽  
David Branski ◽  
Ernst Christensen ◽  
Elisabeth Holme ◽  
...  
Keyword(s):  
Carnitine Palmitoyltransferase ◽  
Metabolic Decompensation ◽  
Carnitine Palmitoyltransferase Ii

An ignored cause of red urine in children: rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency

2017 ◽  
Vol 30 (2) ◽  
Author(s):  
Engin Melek ◽  
Fatma Derya Bulut ◽  
Bahriye Atmış ◽  
Berna Şeker Yılmaz ◽  
Aysun Karabay Bayazıt ◽  
...  
Keyword(s):  
Clinical Phenotype ◽  
Carnitine Palmitoyltransferase ◽  
Long Chain Fatty Acids ◽  
Infantile Form ◽  
Dark Urine ◽  
Recurrent Rhabdomyolysis ◽  
History Of ◽  
Carnitine Palmitoyltransferase Ii ◽  
Cpt Ii Deficiency ◽  
Long Chain

AbstractCarnitine palmitoyltransferase II (CPT-II) deficiency is an autosomal recessively inherited disorder involving the β-oxidation of long-chain fatty acids, which leads to rhabdomyolysis and subsequent acute renal failure. The clinical phenotype varies from a severe infantile form to a milder muscle form. Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise. As no erythrocytes in the microscopic examination of the urine and hemoglobinuria were present, myoglobinuria due to rhabdomyolysis was the most probable cause of dark urine. After excluding the other causes of rhabdomyolysis, with the help of metabolic investigations, the patient was suspected to have CPT-II deficiency, the most common cause of metabolic rhabdomyolysis. Our aim in presenting this case is to emphasize considering rhabdomyolysis in the differential diagnosis of dark urine in order to prevent recurrent rhabdomyolysis and renal injury.

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