scholarly journals A nationwide retrospective observational study of population newborn screening for medium‐chain acyl‐CoA dehydrogenase (MCAD) deficiency in the Netherlands

2019 ◽  
Vol 42 (5) ◽  
pp. 890-897 ◽  
Author(s):  
Emmalie A. Jager ◽  
Myrthe M. Kuijpers ◽  
Annet M. Bosch ◽  
Margot F. Mulder ◽  
Estela R. Gozalbo ◽  
...  
Keyword(s):  
The Netherlands ◽  
Observational Study ◽  
Newborn Screening ◽  
Retrospective Observational Study ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Chain Acyl

scholarly journals Diagnostic potential of stored dried blood spots for inborn errors of metabolism: a metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency

2018 ◽  
Vol 71 (10) ◽  
pp. 885-889 ◽  
Author(s):  
Noriyuki Kaku ◽  
Kenji Ihara ◽  
Yuichiro Hirata ◽  
Kenji Yamada ◽  
Sooyoung Lee ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Inborn Errors Of Metabolism ◽  
Dried Blood Spots ◽  
Screening Tests ◽  
Inborn Errors ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Blood Spots ◽  
Chain Acyl ◽  
Biochemical Analyses

AimIt is estimated that 1–5% of sudden infant death syndrome (SIDS) cases might be caused by undiagnosed inborn errors of metabolism (IEMs); however, the postmortem identification of IEMs remains difficult. This study aimed to evaluate the usefulness of dried blood spots (DBSs) stored after newborn screening tests as a metabolic autopsy to determine the causes of death in infants and children who died suddenly and unexpectedly.MethodsInfants or toddlers who had suddenly died without a definite diagnosis between July 2008 and December 2012 at Kyushu University Hospital in Japan were enrolled in this study. Their Guthrie cards, which had been stored for several years at 4–8°C, were used for an acylcarnitine analysis by tandem mass spectrometry to identify inborn errors of metabolism.ResultsFifteen infants and children who died at less than 2 years of age and for whom the cause of death was unknown were enrolled for the study. After correcting the C0 and C8 values assuming the hydrolysation of acylcarnitine in the stored DBSs, the corrected C8 value of one case just exceeded the cut-off level for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency screening. Genetic and biochemical analyses confirmed this patient to have MCAD deficiency.ConclusionDBSs stored after newborn screening tests are a promising tool for metabolic autopsy. The appropriate compensation of acylcarnitine data and subsequent genetic and biochemical analyses are essential for the postmortem diagnosis of inborn errors of metabolism.

scholarly journals Medium-chain acyl-CoA dehydrogenase deficiency: Two novel ACADM mutations identified in a retrospective screening

2018 ◽  
Vol 46 (4) ◽  
pp. 1339-1348 ◽  
Author(s):  
Andraz Smon ◽  
Urh Groselj ◽  
Marusa Debeljak ◽  
Mojca Zerjav Tansek ◽  
Sara Bertok ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Organic Acids ◽  
Newborn Screening ◽  
Screening Programme ◽  
Clinical Signs ◽  
Newborn Screening Programme ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Expanded Newborn Screening ◽  
Chain Acyl

Objective The aim of this study was to determine whether an expanded newborn screening programme, which is not yet available in Slovenia, would have detected the first two patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in the country. Two novel ACADM mutations are also described. Methods Both patients were diagnosed clinically; follow-up involved analysis of organic acids in urine, acylcarnitines in dried blood spots, and genetic analysis of ACADM. Cut-off values of acylcarnitines in newborns were established using analysis of 10,000 newborns in a pilot screening study. Results In both patients, analysis of the organic acids in urine showed a possible β-oxidation defect, while the specific elevation of acylcarnitines confirmed MCAD deficiency. Subsequent genetic analysis confirmed the diagnosis; both patients were compound heterozygotes, each with one novel mutation (c.861 + 2T > C and c.527_533del). The results from a retrospective analysis of newborn screening cards clearly showed major elevations of MCAD-specific acylcarnitines in the patients. Conclusions An expanded newborn screening programme would be beneficial because it would have detected MCAD deficiency in both patients before the development of clinical signs. Our study also provides one of the first descriptions of ACADM mutations in Southeast Europe.

Prevalence of carriers of the most common medium-chain acyl-CoA dehydrogenase (MCAD) deficiency mutation (G985A) in The Netherlands

1996 ◽  
Vol 98 (1) ◽  
pp. 1-2 ◽  
Author(s):  
H. G. de Vries ◽  
Klary Niezen-Koning ◽  
J. W. Kliphuis ◽  
G. Peter A. Smit ◽  
Hans Scheffer ◽  
...  
Keyword(s):  
The Netherlands ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Chain Acyl

scholarly journals Sudden unexpected infant death (SUDI) in a newborn due to medium chain acyl CoA dehydrogenase (MCAD) deficiency with an unusual severe genotype

2012 ◽  
Vol 38 (1) ◽  
pp. 59 ◽  
Author(s):  
Cristina Lovera ◽  
Francesco Porta ◽  
Anna Caciotti ◽  
Serena Catarzi ◽  
Michela Cassanello ◽  
...  
Keyword(s):  
Infant Death ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Sudden Unexpected Infant Death ◽  
Chain Acyl ◽  
Unexpected Infant Death

Pulmonary haemorrhage and cardiac dysfunction in a neonate with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

2005 ◽  
Vol 94 (1) ◽  
pp. 114-116 ◽  
Author(s):  
K. Maclean ◽  
V. Rasiah ◽  
E. Kirk ◽  
K. Carpenter ◽  
S. Cooper ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Pulmonary Haemorrhage ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Chain Acyl

scholarly journals Rapid diagnosis of MCAD deficiency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry

1997 ◽  
Vol 43 (11) ◽  
pp. 2106-2113 ◽  
Author(s):  
Donald H Chace ◽  
Steven L Hillman ◽  
Johan L K Van Hove ◽  
Edwin W Naylor
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Newborn Screening ◽  
Chain Length ◽  
Filter Paper ◽  
Tandem Mass ◽  
Mcad Deficiency ◽  
Medium Chain ◽  
Blood Spots ◽  
Medium Chain Length

Abstract We report the application of tandem mass spectrometry to prospective newborn screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. MCAD deficiency is diagnosed from dried blood spots on filter paper cards from newborns on the basis of the increase of medium chain length acylcarnitines identified by isotope dilution mass spectrometry methods. A robust and accurate semiautomated method for the analysis of medium chain length acylcarnitines as their butyl esters was developed and validated. Quantitative data from the analyses of 113 randomly collected filter paper blood spots from healthy newborns showed low concentrations of medium chain length acylcarnitines such as octanoylcarnitine. The maximum concentration of octanoylcarnitine was 0.22 μmol/L, with the majority being at or below the detection limit. In all 16 blood spots from newborns with confirmed MCAD deficiency, octanoylcarnitine was highly increased [median 8.4 μmol/L (range 3.1–28.3 μmol/L)], allowing easy detection. The concentration of octanoylcarnitine was significantly higher in these 16 newborns (<3 days of age) than in 16 older patients (ages 8 days to 7 years) with MCAD deficiency (median 1.57 μmol/L, range 0.33–4.4). The combined experience of prospective newborn screening in Pennsylvania and North Carolina has shown a disease frequency for MCAD deficiency of 1 in 17 706. No false-positive and no known false-negative results have been found. A validated method now exists for prospective newborn screening for MCAD deficiency.

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