Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning

Therrell, Bradford L.; Lloyd-Puryear, Michele A.; Camp, Kathryn M.; Mann, Marie Y.

doi:10.1016/j.ymgme.2014.07.009

Cited by 99 publications

(82 citation statements)

References 22 publications

(24 reference statements)

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“…60,65 Taking all the reported cases detected by NBS in the USA from 2001 to 2010, the incidence of MCAD was 1 in 17,759. 66 In Massachusetts, approximately 1 out of 15,000 infants screened was diagnosed with MCAD, almost identical to the 1:14,000 frequency of phenylketonuria. 31 In Pennsylvania and Bavaria, the MCAD frequency from the introduction of NBS has been estimated to be even greater at 1:8,000 and 1:9,000, respectively.…”

Section: Molecular Aspectsmentioning

confidence: 99%

Screening for medium-chain acyl CoA dehydrogenase deficiency: current perspectives

Soler‐Alfonso¹,

Bennett²,

Fıçıcıoğlu³

2016

RRN

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Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder associated with fatty acid oxidation. The disorder is characterized by inability to generate sufficient energy from fatty acid metabolism during periods of catabolic stress caused by intercurrent illness or prolonged fasting. The metabolic consequences are severe and include hypoketotic hypoglycemia leading to a Reye-like hepatic encephalopathy syndrome and sudden death. If individuals are detected before a life-threatening episode, the complications of MCAD deficiency are preventable. Newborn metabolic screening enables the early detection of MCAD deficiency in many countries worldwide. The metabolic marker for MCAD deficiency "octanoylcarnitine" (C8) can be detected with a high degree of sensitivity in the newborns by tandem mass spectrometry. The 985A.G (K329E) mutation accounts for the majority of disease alleles, and approximately 47%-80% of MCAD patients are homozygotes for this mutation. Newborns homozygous for the 985A.G mutation have higher octanoylcarnitine levels than those who are heterozygous for 985A.G mutation or possess other genotypes. Time of sampling after birth and prematurity may affect the octanoylcarnitine levels in MCAD-deficient newborns. Tandem mass spectrometry newborn blood spot screening for MCAD deficiency is accurate and effective, and reduces morbidity and mortality in affected children.

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Section: Molecular Aspectsmentioning

confidence: 99%

Screening for medium-chain acyl CoA dehydrogenase deficiency: current perspectives

Soler‐Alfonso¹,

Bennett²,

Fıçıcıoğlu³

2016

RRN

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“…A recent study by Therrell et al [10] found that the frequency of primary carnitine deficiency among newborn screening programs in the USA is 1: 142,000. However, the frequency of mutations (nonsense, splicing and expressed missense only) in 60,000 normal individuals (carriers) in the exac browser (http://exac.broadinstitute.…”

Section: Shortcomings Of Newborn Screeningmentioning

confidence: 99%

“…The incidence of primary carnitine deficiency varies with a frequency of approximately 1: 40,000 newborns in Japan [8] , 1: 37,000-1: 100,000 newborns in Australia [9] and 1: 142,000 in the USA [10] . The highest incidence (1: 300) has been reported in the Faroe Islands, an archipelago that remained geographically isolated for centuries [11] .…”

Section: The Need To Screen For and Treat Primary Carnitine Deficiencymentioning

confidence: 99%

Primary Carnitine Deficiency and Newborn Screening for Disorders of the Carnitine Cycle

Longo¹

2016

Ann Nutr Metab

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Carnitine is needed for transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent β-oxidation. Carnitine can be synthesized by the body and is also obtained in the diet through consumption of meat and dairy products. Defects in carnitine transport such as those caused by defective activity of the OCTN2 transporter encoded by the SLC22A5 gene result in primary carnitine deficiency, and newborn screening programmes can identify patients at risk for this condition before irreversible damage. Initial biochemical diagnosis can be confirmed through molecular testing, although direct study of carnitine transport in fibroblasts is very useful to confirm or exclude primary carnitine deficiency in individuals with genetic variations of unknown clinical significance or who continue to have low levels of carnitine despite negative molecular analyses. Genetic defects in carnitine biosynthesis do not generally result in low plasma levels of carnitine. However, deletion of the trimethyllysine hydroxylase gene, a key gene in carnitine biosynthesis, has been associated with non-dysmorphic autism. Thus, new roles for carnitine are emerging that are unrelated to classic inborn errors of metabolism.

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“…Primary carnitine deficiency has a frequency of 1:40,000 in Japan [12], 1:120,000 in Australia [13] and 1:140,000 in the USA [14]. The disease is very common in the Faroe Islands with a prevalence of 1:300 [15].…”

Section: Molecular Bases and Prevalence Of Primary Carnitine Deficiencymentioning

confidence: 99%

Neonatal Screening for Primary Carnitine Deficiency: Lessons Learned from the Faroe Islands

Steuerwald

Lund

Rasmussen

et al. 2017

IJNS

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Primary carnitine deficiency is caused by the defective OCTN2 carnitine transporter encoded by the SLC22A5 gene. A lack of carnitine impairs fatty acid oxidation resulting in hypoketotic hypoglycemia, hepatic encephalopathy, skeletal and cardiac myopathy, and arrhythmia. This condition can be detected by finding low levels of free carnitine (C0) in neonatal screening. Mothers with primary carnitine deficiency can also be identified by low carnitine levels in their infant by newborn screening. Primary carnitine deficiency is rare (1:40,000-1:140,000 newborns) except in the Faroe Islands (1:300) due to a founder effect. A specific mutation (c.95A>G, p.N32S) is prevalent, but not unique, with three additional mutations (c.131C>T/p.A44V, a splice mutation c.825-52G>A, and a risk-haplotype) recently identified in the Faroese population. In the Faroe Islands, several adult patients suffered sudden death from primary carnitine deficiency leading to the implementation of a nationwide population screening (performed after 2 months of age) in addition to universal neonatal screening. While most affected infants can be identified at birth, some patients with primary carnitine deficiency might be missed by the current neonatal screening and could be better identified with a repeated test performed after 2 months of age.

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Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning

Cited by 99 publications

References 22 publications

Screening for medium-chain acyl CoA dehydrogenase deficiency: current perspectives

Screening for medium-chain acyl CoA dehydrogenase deficiency: current perspectives

Primary Carnitine Deficiency and Newborn Screening for Disorders of the Carnitine Cycle

Neonatal Screening for Primary Carnitine Deficiency: Lessons Learned from the Faroe Islands

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