Cyclic vomiting syndrome versus inborn errors of metabolism: A review with clinical recommendations

Abstract

Structured Abstract Background Inborn errors of metabolism are on the differential for patients presenting with a cyclic vomiting syndrome phenotype. Classes of disorders to consider include: mitochondrial disorders, fatty acid oxidation disorders, urea cycle defects, organic acidurias and acute intermittent porphyria. Aim This article reviews the metabolic differential diagnosis and approach to screening for inborn errors in children and adults presenting with a cyclic or recurrent vomiting phenotype. Conclusion Cyclic vomiting syndrome is thought to be an episodic syndrome that may be associated with migraine. It is a diagnosis of exclusion. Inborn errors of metabolism should be considered in the patient presenting with a recurrent vomiting phenotype. Mitochondrial dysfunction may play a role in cyclic vomiting syndrome, and true mitochondrial disorders can present with a true cyclic vomiting phenotype.

Cyclic vomiting syndrome: Pathophysiology, comorbidities, and future research directions

“…Further, these mitochondrial associations have not been replicated in adults with CVS suggesting the role of other non‐mitochondrial factors in adult CVS patients. Inborn errors of metabolism, including fatty acid oxidation disorders and urea cycle defects, have been associated with pediatric CVS . Recent studies found that ion channel polymorphisms (RYR2, SCN4A) that impact cellular stress responses may be associated with CVS .…”

“…In addition to acquiring new information from validated survey instruments, it will be useful to adopt a standardized panel of biomarkers from patient specimens to gain insight into CVS pathophysiology. Studies in small cohorts employing blood, urine, and saliva samples to quantify neurohumoral and metabolic functions and genetic profiles of mitochondrial DNA and ion channel distributions, and functional MRI imaging methodologies to discern altered CNS signaling have identified factors which may be of importance in some CVS subsets . Broad‐based application of biomarker panels including these and other testing across multiple centers in diverse CVS patient populations will delineate the relevance of these and other parameters in modifying the clinical presentation of this disorder.…”

“…Inborn errors of metabolism, including fatty acid oxidation disorders and urea cycle defects, have been associated with pediatric CVS. 26 Recent studies found that ion channel polymorphisms (RYR2, SCN4A) that impact cellular stress responses may be associated with CVS. 13 The synergic roles of nuclear DNA mutations (identified by NextGen sequencing) that impact the function of ion channels, axonal transport (KIF1B), or energy production (TRAP1) have been investigated in children with CVS.…”

Recurrent Severe Vomiting in a 7-year-old boy

“…9 Vomiting often starts in the early morning 10 and can last from hours to days. 1 It is commonly associated with listlessness and pallor 2…”

“…commonly have a personal or family history of migraine, as in the case of L. 1,3,9 CVS is classi ed by the American Headache Society as an "episodic syndrome that may be associated with migraine" under the ICHD III beta classi cation. 3 It most commonly a ects children aged 5 to 7 years.…”