Objectives: Determination of methylmalonic acid (MMA) from dried blood spots (DBS) is commonly performed in clinical diagnostics and newborn screening for propionic acidemia (PA) and methylmalonic acidemia. Isobaric compounds of MMA having the same mass can affect diagnostic reliability and quantitative results, which represents a previously unrecognized pitfall in clinical assays for MMA. We set out to identify interfering substances of MMA in DBS, serum and urine samples from confirmed patients with PA and methylmalonic acidemia.
Methods: Techniques included quadrupole time-of-flight high-resolution mass spectrometry (QTOF HR-MS), nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography (LC) and tandem mass spectrometry (MS/MS).
Results: The five isobaric metabolites detected in DBS, serum and urine from PA and methylmalonic acidemia patients were confirmed as 2-methyl-3-hydroxybutyrate, 3-hydroxyisovalerate, 2-hydroxyisovalerate, 3-hydroxyvalerate and succinate using a series of experiments. An additional unknown substance with low abundance remained unidentified.
Conclusions: The presented results facilitate the diagnostic and quantitative reliability of the MMA determination in clinical assays. Isobaric species should be investigated in assays for MMA to eliminate possible interference in a wide range of conditions including PA, methylmalonic acidemia, a vitamin B deficiency, ketosis and lactic acidosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.clinbiochem.2022.09.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of a biallelic MMUT variant (p.Thr230Arg) and its global perspective on clinical management.
Mol Biol Rep
December 2024
Translational Genomics Laboratory, COMSATS University Islamabad, Taramri Chock, Park Road, Islamabad, 45550, Pakistan.
Background: Methylmalonic acidemia (MMA), type mut (0) is a rare type of genetic inborn error of metabolism (IEM) that is caused by aberrant malonyl-CoA mutase activity. Diagnosing IEM can be challenging due to its inherited onset and varying degrees of severity.
Methods And Results: In the present study, a consanguineous Pakistani family suspected of IEM was genetically analyzed using whole exome sequencing.
Clinical Practice Recommendations on Kidney Management in Methylmalonic Acidemia: an Expert Consensus Statement From ERKNet and MetabERN.
Kidney Int Rep
December 2024
Division of Metabolic Diseases and Hepatology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Methylmalonic acidemias (MMAs) are rare inherited metabolic diseases with multiorgan involvement. Chronic kidney disease (CKD) is a common complication, leading to kidney failure, dialysis, and kidney transplantation (KT). The objective of these guidelines was to develop clinical practice recommendations focusing on specific aspects of the kidney management of this disease.
View Article and Find Full Text PDFRole of carglumic acid in the long-term management of propionic and methylmalonic acidurias.
Orphanet J Rare Dis
December 2024
Pediatric Unit, Reference Center for Inborn Errors of Metabolism, University Hospital of Nancy, INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy, University of Lorraine, Nancy, France.
Propionic aciduria (PA) and methylmalonic aciduria (MMA) are rare inherited disorders caused by defects in the propionate metabolic pathway. PA due to propionyl coenzyme A carboxylase deficiency results in accumulation of propionic acid, while in MMA, deficiency in methylmalonyl coenzyme A mutase leads to accumulation of methylmalonic acid. Hyperammonemia is related to a secondary deficiency of N-acetylglutamate (NAG), the activator of carbamoyl phosphate synthetase 1, which is an irreversible rate-limiting enzyme in the urea cycle.
View Article and Find Full Text PDFSpectrum analysis of inborn errors of metabolism for expanded newborn screening in Xinjiang, China.
PeerJ
December 2024
Prenatal Diagnosis Center, Urumqi Maternal and Child Health Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China.
To determine the disease spectrum and genetic characteristics of inborn errors of metabolism (IEM) in Xinjiang province in the northwest of China, 41,690 newborn babies were screening by tandem mass spectrometry from November 2018 to December 2021. Of these, 57 newborn babies were referred for genetic analysis by next-generation sequencing, which was validated by Sanger sequencing. A total of 36 newborn babies and one relative were diagnosed with IEM, and the overall positive predictive value was 29.
View Article and Find Full Text PDFClinical spectrum and genetic variation of six patients with methylmalonic aciduria (MMA); a report from Iran.
BMC Pediatr
December 2024
Shiraz Transplant Research Center (STRC), Shiraz University of Medical Sciences, Shiraz, Iran.
Objective: Methylmalonic acidemia (MMAs) is known as a severe, complex, and lethal disorder of methylmalonate and cobalamin. The patients with MMA may have developmental, neurological, and metabolic disorders such as liver disease. Here, we aim to evaluate 6 Iranian patients suspected to MMA disorder.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!