A Delphi clinical practice protocol for the management of very long chain acyl-CoA dehydrogenase deficiency

Arnold, Georgianne L.; Hove, Johan Van; Freedenberg, Debra; Strauss, Arnold W.; Longo, Nicola; Burton, Barbara K.; Garganta, Cheryl; Fıçıcıoğlu, Can; Cederbaum, Stephen D.; Harding, Cary O.; Boles, Richard G.; Matern, Dietrich; Chakraborty, Pranesh; Feigenbaum, Annette

doi:10.1016/j.ymgme.2008.09.008

Cited by 141 publications

(117 citation statements)

References 25 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…A systematic use of this tool to integrate biochemical and enzymatic results in cases with inconclusive genotyping results has the potential to resolve existing differences of opinion regarding the proper way to follow up an abnormal newborn screening result. 19,20 The in vitro work is beyond the scope of this report and will be published separately (E.H. Smith, D. Matern, et al, unpublished data).…”

Section: Score Is < 10mentioning

confidence: 99%

Enhanced interpretation of newborn screening results without analyte cutoff values

Marquardt

Currier

McHugh

et al. 2012

Genetics in Medicine

Self Cite

116

View full text Add to dashboard Cite

Purpose: To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries. Methods: A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors. Results: Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events. Conclusions: Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%

show abstract

Section: Score Is < 10mentioning

confidence: 99%

Enhanced interpretation of newborn screening results without analyte cutoff values

Marquardt

Currier

McHugh

et al. 2012

Genetics in Medicine

Self Cite

116

View full text Add to dashboard Cite

show abstract

“…7 Because these patients are considered to be at risk of potentially life-threatening symptoms, parents often get dietary advice, including strict avoidance of fasting. 8 However, since the introduction of VLCADD in NBS panels, it has become clear that a significant number of newborns with VLCADD actually have a very low risk for metabolic decompensation and may even remain fully asymptomatic if left untreated. [9][10][11] Unfortunately, there is currently no reliable method to assess the expected phenotypic severity at the time of diagnosis through NBS.…”

Section: Introductionmentioning

confidence: 99%

Fatty acid oxidation flux predicts the clinical severity of VLCAD deficiency

Diekman

Ferdinandusse

Pol

et al. 2015

Genetics in Medicine

View full text Add to dashboard Cite

Purpose: Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is an inherited disorder of mitochondrial long-chain fatty acid β-oxidation (LC-FAO) and is included in many newborn screening (NBS) programs worldwide. Patients may present with hypoketotic hypoglycemia, cardiomyopathy, and/or myopathy, but clinical severity varies widely and the clinical outcome is unpredictable. We investigated predictive markers that may determine clinical severity. Methods:We developed a clinical severity score (CSS), which was determined for 13 Dutch patients with VLCADD, all of whom were diagnosed before the introduction of VLCADD in NBS to prevent bias from early diagnosis. In cultured skin fibroblasts from these patients, we measured LC-FAO flux (the rate of oleate oxidation), VLCAD activity, and acylcarnitine profiles following palmitate loading. Results:The strongest correlation (r = 0.93; P < 0.0001) was observed between LC-FAO flux and the CSS. VLCAD activity measurement and the C14/C16-to-acylcarnitine ratio correlated much less. A median LC-FAO flux of 6% of control values (range 5.6-6.8%) was associated with cardiomyopathy (P < 0.01), and 32.4% (range 5.6-50.5%) was associated with myopathy (P < 0.05). Conclusion:Our results demonstrate a very strong correlation between LC-FAO flux in fibroblasts and the clinical severity of VLCADD. LC-FAO flux measurements may thus predict whether patients are likely to develop symptoms.

show abstract

“…VLCADD is an autosomal recessive d i s o r d e r w i t h a n e s t i m a t e d p r e v a l e n c e o f 1:31,500-1:85,000 (Lindner et al 2010;Arnold et al 2009). The disorder is highly variable, and ranges from severe infantile disease to completely asymptomatic elderly individuals.…”

Section: Introductionmentioning

confidence: 99%

“…During catabolic circumstances such as prolonged fasting, stress, illness, and surgery, metabolic derangement can occur, resulting in hypoglycemia, myopathies (including cardiomyopathy), metabolic acidosis, and rhabdomyolysis (Leslie et al 1993;Redshaw and Stewart 2014). Current treatment consists of avoiding catabolism with regular feedings and in some patients a restriction of long chain fatty acids, supplementation of medium chain triglycerides, and frequent carbohydrate intake to prevent activation of fatty acid metabolism (Arnold et al 2009;Das et al 2010). The metabolic derangement during surgery depends, amongst others, on disease severity which is related to residual enzyme activity.…”

Section: Introductionmentioning

confidence: 99%

Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency and Perioperative Management in Adult Patients

et al. 2016

View full text Add to dashboard Cite

Surgery and anesthesia pose a threat to patients with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), because prolonged fasting, stress, and pain are known risk factors for the induction of metabolic derangement. The optimal perioperative management in these patients is unknown and the use of volatile agents and agents dissolved in fatty acids has been related to postoperative metabolic complications. However, the occurrence of metabolic derangement is multifactorial and depends, amongst others, on the severity of the mutation and residual enzyme activity. Current guidelines suggest avoiding both volatile anesthetics as well as propofol, which seriously limits the options for providing safe anesthesia. Therefore, we reviewed the available literature on the perioperative management of patients with VLCADD. We concluded that the use of some medications, such as volatile anesthetics, in patients with VLCADD might be wrongfully avoided and could in fact prevent metabolic derangement by the adequate suppression of pain and stress during surgery. We will illustrate this with a case report of an adult VLCADD patient undergoing minor surgery. Besides the use of remifentanil, anesthesia was uneventfully maintained with the use of sevoflurane, a volatile agent, and continuous glucose infusion. The patient was monitored with a continuous glucose meter and creatinine kinase measurements.

show abstract

A Delphi clinical practice protocol for the management of very long chain acyl-CoA dehydrogenase deficiency

Cited by 141 publications

References 25 publications

Enhanced interpretation of newborn screening results without analyte cutoff values

Enhanced interpretation of newborn screening results without analyte cutoff values

Fatty acid oxidation flux predicts the clinical severity of VLCAD deficiency

Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency and Perioperative Management in Adult Patients

Contact Info

Product

Resources

About