Plasma Acylcarnitine and Urinary Organic Acid Profiling for the diagnosis of Fatty Acid Oxidation Disorder and Organic Acidurias using tandem mass spectrometry (MS/MS) and gas chromatography tandem with mass spectrometry (GC-MS): a retrospective study

INTRODUCTION@#Acylcarnitines in plasma and urinary organic acids are essential diagnostic markers for some Inborn Errors of Metabolism (IEM) such as fatty acid oxidation disorders, and disorders related to organic acids metabolism. By virtue of R. A. 9288, Filipino newborn babies are screened for inherited metabolic disorders via the analysis of dried blood spots (DBS) using MS/MS. @*OBJECTIVE@#This study aimed to establish the plasma acylcarnitine (PLAC) and urinary organic acid (UOA) profiles of Filipino newborn babies screened at high risk for IEMS using MS/MS and single quadrupole GC-MS analytical techniques. Further, this study describes the process of determining the true positive cases of fatty acid oxidation disorders and some organic acidurias among screened Filipino newborn babies using different sample types such as plasma and urine via flow injection analysis with tandem mass spectrometry (FIA-MS/MS) and another technique such as gas chromatography in tandem with mass spectrometry (GC-MS).@*METHODOLOGY@#Plasma acylcarnitine and urinary organic acid analyses were performed using Waters® MS/MS and Agilent® single quadrupole GC-MS, respectively. Results obtained from PLAC and UOA databases and IEM registry of the Biochemical Genetics Laboratory (BGL) covering the period 2015-2021 were utilized to account for the number of confirmed cases out of the total number screened positive for IEMs. Descriptive statistics was also used to evaluate the detection rates of FAODs and Organic Acidurias in Filipino newborn babies screened to be high risk.@*RESULTS@#Plasma acylcarnitine analysis was introduced by BGL only in 2015. Data from 2015-2021, indicated 176 true positives out of 1642 babies screened at high risk for FAODs and organic acidurias. The use of plasma and urine samples for measurements in MS/MS and GC-MS yielded a detection rate of 10.7% with 104 Filipino newborn babies afflicted with fatty acid oxidation disorders (FAOD) while 72 were found to be confirmed cases of organic acidurias. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was reported to be the most common FAOD with 67 cases. Organic acidurias such as glutaric aciduria type 1 and 3-Methylcrotonyl-CoA carboxylase (3-MCC) deficiency were found to be common with 34 and 26 true positives, respectively. @*CONCLUSION@#The plasma acylcarnitine and urinary organic acid profiles of Filipino newborn babies with fatty acid oxidation disorders and organic acidurias obtained via MS/MS and GC/MS, respectively, were presented in this paper. This study emphasizes the importance of conducting confirmatory testing to establish the true positives from among those Filipino newborns flagged to be at high risk for FAODs or organic aciduria. The confirmatory tests are based on the use of different samples such as urine and plasma in order to detect and quantify biomarkers for FAODs and organic acidurias using two different analytical techniques such as MS/MS and GC-MS. This study warrants further studies directed towards the validation of analytical methodologies for targeted measurements of biomarkers of IEMS in urine and plasma of newborn babies to increase the efficiency of establishing true positives and to determine the efficiency of administration of interventions on Filipino children with genetic disabilities, that is, for monitoring purposes.

L-2-Hydroxyglutaric Aciduria - A rare type of organic Aciduria presenting as seizures and developmental delay in a Filipino child

@#L-2-hydroxyglutaric aciduria (L-2-HGA) is a rare, autosomal recessive organic aciduria with increased levels of L-2hydroxyglutaric acid in the urine and other body fluids. Clinical presentation includes developmental delay, epilepsy, and typical neuroimaging findings. This is a report of the clinical, neuroimaging, and biochemical findings of the first diagnosed case of L-2-hydroxyglutaric aciduria in the Philippines. This paper likewise reaffirms the importance of locally available biochemical tests in diagnosing inborn error of metabolism.

A review of the results of the very long chain fatty acid analyses for X-linked Adrenoleukodystrophy at the Biochemical Genetics Laboratory of the Institute of Human Genetics-National Institutes of Health, Manila

@#Background. X-linked adrenoleukodystrophy (X-ALD) is a progressive genetic disorder affecting the metabolism of very long chain fatty acids in the adrenal glands, spinal cord and white matter of the nervous system. It is an inherited metabolic storage disease whereby a defect in a specific enzyme results in the accumulation of very long-chain fatty acids (VLCFA) that are harmful to some cells and organs. VLCFA analysis for confirmation of X-linked adrenoleukodystrophy is one of the most requested tests among the send-out laboratory services of the Biochemical Genetics Laboratory at the Institute of Human Genetics. This paper aims to review the clinical characteristics and the results of the VLCFA analysis of the patients whose samples we received for testing.Methods. Overseas tests samples received by the Biochemical Genetics Laboratory for VLCFA from 2002-2016 were included. The details of the patients were collated in an overseas tests database and was the main source of the data for this study. The results of the VLCFA tests sent to the Kennedy Krieger Institute and The Children’s Hospital at Westmead were inputted into the said database. Descriptive statistics was utilized in order to examine the clinical and biochemical data of the patients.Results. The results showed that out of the 54 samples submitted to our laboratory, 19 (35%) of the samples received from male patients suspected to have X-ALD yielded positive results and another 10 (19%) females were found to be carriers. Visual defect followed by deteriorating mental status were the most frequent indications for VLCFA testing. Conclusion. Having a significant diagnostic yield of 54%, early diagnosis of X-linked adrenoleukodystrophy in our population is important so that proper management that could prevent the progression of the disease could be timely instituted.