Performance of serum and dried blood spot acylcarnitine profiles for detection of fatty acid β-oxidation disorders in adult patients with rhabdomyolysis

Khalid Al-Thihli, Graham Sinclair, Sandra Sirrs, Michelle Mezei, Judie Nelson, Hilary Vallance

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Plasma/serum and dried blood spot (DBS) acylcarnitine profiles (ACPs) are key to the diagnosis of mitochondrial fatty acid β-oxidation disorders (FAODs). Despite their significant clinical applications, limited published data exists to compare their sensitivities and specificities. We retrospectively evaluated these two methods in adult patients with a history of rhabdomyolysis; investigated for an underlying FAOD. Methods: A retrospective study was completed for adult patients (investigated between 2003 and 2011) meeting the inclusion criteria of a history of recurrent rhabdomyolysis or one episode of rhabdomyolysis with a history of exercise intolerance. All subjects underwent investigations for an underlying FAOD including DBS and serum ACP analysis concurrently collected during a symptom-free period, and skin biopsy for cultured fibroblast fatty acid oxidation studies or enzyme activity measurement, as indicated, with or without molecular confirmation. Their medical records were reviewed, and the performance of the two methods were compared. Results: Seven out of 31 subjects (22.6 %) were diagnosed with an underlying FAOD. Long chain acylcarnitines were more markedly elevated in serum samples from confirmed CPTII cases (n∈=∈4) as compared to matched DBS profiles. The sensitivity and specificity of DBS ACP was 71.4 % (95 % CI, 0.30-0.95) and 100 % (95 % CI, 0.79-1.00), respectively, compared to a sensitivity of 100 % (95 % CI, 0.56-1.00) and a specificity of 94.7 % (95 % CI, 0.72-1.00) for serum ACP. Conclusion: FAODs appear to be a common cause of recurrent rhabdomyolysis or rhabdomyolysis with a history of exercise induced myalgia. At least historically, FAODs maybe underdiagnosed in adults with rhabdomyolysis. This study suggests that serum ACP might be more sensitive than DBS ACP for detection of an underlying FAOD in adults with rhabdomyolysis while asymptomatic.

Original languageEnglish
Pages (from-to)207-213
Number of pages7
JournalJournal of Inherited Metabolic Disease
Volume37
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Rhabdomyolysis
Fatty Acids
Serum
Exercise
Sensitivity and Specificity
acylcarnitine
Myalgia
Medical Records
Retrospective Studies
Fibroblasts
Biopsy
Skin
Enzymes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

Performance of serum and dried blood spot acylcarnitine profiles for detection of fatty acid β-oxidation disorders in adult patients with rhabdomyolysis. / Al-Thihli, Khalid; Sinclair, Graham; Sirrs, Sandra; Mezei, Michelle; Nelson, Judie; Vallance, Hilary.

In: Journal of Inherited Metabolic Disease, Vol. 37, No. 2, 2014, p. 207-213.

Research output: Contribution to journalArticle

@article{f0d3bed2267c46fd8ddb677cb2467c62,
title = "Performance of serum and dried blood spot acylcarnitine profiles for detection of fatty acid β-oxidation disorders in adult patients with rhabdomyolysis",
abstract = "Background: Plasma/serum and dried blood spot (DBS) acylcarnitine profiles (ACPs) are key to the diagnosis of mitochondrial fatty acid β-oxidation disorders (FAODs). Despite their significant clinical applications, limited published data exists to compare their sensitivities and specificities. We retrospectively evaluated these two methods in adult patients with a history of rhabdomyolysis; investigated for an underlying FAOD. Methods: A retrospective study was completed for adult patients (investigated between 2003 and 2011) meeting the inclusion criteria of a history of recurrent rhabdomyolysis or one episode of rhabdomyolysis with a history of exercise intolerance. All subjects underwent investigations for an underlying FAOD including DBS and serum ACP analysis concurrently collected during a symptom-free period, and skin biopsy for cultured fibroblast fatty acid oxidation studies or enzyme activity measurement, as indicated, with or without molecular confirmation. Their medical records were reviewed, and the performance of the two methods were compared. Results: Seven out of 31 subjects (22.6 {\%}) were diagnosed with an underlying FAOD. Long chain acylcarnitines were more markedly elevated in serum samples from confirmed CPTII cases (n∈=∈4) as compared to matched DBS profiles. The sensitivity and specificity of DBS ACP was 71.4 {\%} (95 {\%} CI, 0.30-0.95) and 100 {\%} (95 {\%} CI, 0.79-1.00), respectively, compared to a sensitivity of 100 {\%} (95 {\%} CI, 0.56-1.00) and a specificity of 94.7 {\%} (95 {\%} CI, 0.72-1.00) for serum ACP. Conclusion: FAODs appear to be a common cause of recurrent rhabdomyolysis or rhabdomyolysis with a history of exercise induced myalgia. At least historically, FAODs maybe underdiagnosed in adults with rhabdomyolysis. This study suggests that serum ACP might be more sensitive than DBS ACP for detection of an underlying FAOD in adults with rhabdomyolysis while asymptomatic.",
author = "Khalid Al-Thihli and Graham Sinclair and Sandra Sirrs and Michelle Mezei and Judie Nelson and Hilary Vallance",
year = "2014",
doi = "10.1007/s10545-012-9578-7",
language = "English",
volume = "37",
pages = "207--213",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "2",

}

TY - JOUR

T1 - Performance of serum and dried blood spot acylcarnitine profiles for detection of fatty acid β-oxidation disorders in adult patients with rhabdomyolysis

AU - Al-Thihli, Khalid

AU - Sinclair, Graham

AU - Sirrs, Sandra

AU - Mezei, Michelle

AU - Nelson, Judie

AU - Vallance, Hilary

PY - 2014

Y1 - 2014

N2 - Background: Plasma/serum and dried blood spot (DBS) acylcarnitine profiles (ACPs) are key to the diagnosis of mitochondrial fatty acid β-oxidation disorders (FAODs). Despite their significant clinical applications, limited published data exists to compare their sensitivities and specificities. We retrospectively evaluated these two methods in adult patients with a history of rhabdomyolysis; investigated for an underlying FAOD. Methods: A retrospective study was completed for adult patients (investigated between 2003 and 2011) meeting the inclusion criteria of a history of recurrent rhabdomyolysis or one episode of rhabdomyolysis with a history of exercise intolerance. All subjects underwent investigations for an underlying FAOD including DBS and serum ACP analysis concurrently collected during a symptom-free period, and skin biopsy for cultured fibroblast fatty acid oxidation studies or enzyme activity measurement, as indicated, with or without molecular confirmation. Their medical records were reviewed, and the performance of the two methods were compared. Results: Seven out of 31 subjects (22.6 %) were diagnosed with an underlying FAOD. Long chain acylcarnitines were more markedly elevated in serum samples from confirmed CPTII cases (n∈=∈4) as compared to matched DBS profiles. The sensitivity and specificity of DBS ACP was 71.4 % (95 % CI, 0.30-0.95) and 100 % (95 % CI, 0.79-1.00), respectively, compared to a sensitivity of 100 % (95 % CI, 0.56-1.00) and a specificity of 94.7 % (95 % CI, 0.72-1.00) for serum ACP. Conclusion: FAODs appear to be a common cause of recurrent rhabdomyolysis or rhabdomyolysis with a history of exercise induced myalgia. At least historically, FAODs maybe underdiagnosed in adults with rhabdomyolysis. This study suggests that serum ACP might be more sensitive than DBS ACP for detection of an underlying FAOD in adults with rhabdomyolysis while asymptomatic.

AB - Background: Plasma/serum and dried blood spot (DBS) acylcarnitine profiles (ACPs) are key to the diagnosis of mitochondrial fatty acid β-oxidation disorders (FAODs). Despite their significant clinical applications, limited published data exists to compare their sensitivities and specificities. We retrospectively evaluated these two methods in adult patients with a history of rhabdomyolysis; investigated for an underlying FAOD. Methods: A retrospective study was completed for adult patients (investigated between 2003 and 2011) meeting the inclusion criteria of a history of recurrent rhabdomyolysis or one episode of rhabdomyolysis with a history of exercise intolerance. All subjects underwent investigations for an underlying FAOD including DBS and serum ACP analysis concurrently collected during a symptom-free period, and skin biopsy for cultured fibroblast fatty acid oxidation studies or enzyme activity measurement, as indicated, with or without molecular confirmation. Their medical records were reviewed, and the performance of the two methods were compared. Results: Seven out of 31 subjects (22.6 %) were diagnosed with an underlying FAOD. Long chain acylcarnitines were more markedly elevated in serum samples from confirmed CPTII cases (n∈=∈4) as compared to matched DBS profiles. The sensitivity and specificity of DBS ACP was 71.4 % (95 % CI, 0.30-0.95) and 100 % (95 % CI, 0.79-1.00), respectively, compared to a sensitivity of 100 % (95 % CI, 0.56-1.00) and a specificity of 94.7 % (95 % CI, 0.72-1.00) for serum ACP. Conclusion: FAODs appear to be a common cause of recurrent rhabdomyolysis or rhabdomyolysis with a history of exercise induced myalgia. At least historically, FAODs maybe underdiagnosed in adults with rhabdomyolysis. This study suggests that serum ACP might be more sensitive than DBS ACP for detection of an underlying FAOD in adults with rhabdomyolysis while asymptomatic.

UR - http://www.scopus.com/inward/record.url?scp=84898825491&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84898825491&partnerID=8YFLogxK

U2 - 10.1007/s10545-012-9578-7

DO - 10.1007/s10545-012-9578-7

M3 - Article

VL - 37

SP - 207

EP - 213

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - 2

ER -