ABSTRACT
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.
Subject(s)
Plasma , Tandem Mass SpectrometryABSTRACT
@#Introduction: Modular diets (MDs) with low amount of offending amino acids have been developed using locally available food ingredients as alternatives to commercial formulas for the treatment of branched-chain organic acidurias (BCOAs). Herein, we conducted a clinical investigation of MDs in patients with BCOAs. Methods: Modular diet A (MDA), with low leucine was produced for maple syrup urine disease (MSUD), and modular diet B (MDB) products, MDB-1, -2, -3, and -4, with low leucine, valine, methionine and threonine were made for isovaleric aciduria (IVA)/methylmalonic aciduria (MMA)/propionic aciduria (PA). Children aged 4-18 years, with MSUD, IVA, PA or MMA were invited to participate in the study. The research subjects switched from metabolic formula protocol to modular diet protocol. They were followed-up at 0, 1, 2, 4, and 6 months. Clinical efficacies of MDs were determined by completion of study, compliance to MDs, clinical outcomes and complications, and parental satisfaction. Results: Six children (2 MSUD and 4 IVA) participated and completed the study. Compliance to MDA was 100% in MSUD subjects with G-tube feeding, while compliance to MDB varied among self-fed individuals with IVA. One subject with MSUD was clinically stable throughout the study, while the other experienced metabolic instability. All IVA individuals showed clinical and laboratory stability during the study. One MSUD and three IVA families preferred the metabolic formula, whereas the other IVA family reported no preference and the other MSUD subject preferred MDs. Conclusion: We provided a proof of concept in developing modular diets for BCOAs, and showed favourable outcomes when using MDs in IVA and varying clinical benefits in MSUD.
ABSTRACT
Organic acidurias(OA)are a group of diseases that cause carboxylic acid accumulation due to some enzyme deficiencies in the metabolic process,and they are also one of the most common hereditary metabolic diseases. The clinical characteristics of this kind of disease lack specificity and acute attack can occur under some metabolic pressures,such as metabolic acidosis,hypoglycemia,hyperammonia,acute encephalopathy,and even sudden death. With the development of tandem mass spectrometry and gas phase mass spectrometry,and the prevalence of screening for genetic metabolic diseases in neonates,more and more OA have been discovered and enough attention has been paid to this disease by medical workers. The relationship between organic acid metabolic diseases with sudden death and critical illness was analyzed in this paper.
ABSTRACT
@#Introduction: Branched-chain organic acidurias include maple syrup urine disease (MSUD), isovaleric acidemia (IVA), propionic acidemia (PA), and methylmalonic acidemia (MMA). Long term management requires diets of adequate energy and protein with restriction of the offending amino acids. Standard commercial formulas are expensive and unaffordable to patients of low socio-economic status. Methods: This study aimed to develop food products for branched-chain organic acidurias children aged 4-15 years using locally available raw materials in Thailand. Fish maw (Pangasius hypophthalmus) and roasted sunflower kernel (Helianthus annuus) were selected as protein sources due to their low leucine contents. Five formulations were developed, namely (i) powder (low leucine, isoleucine, and valine for MSUD) for tube feeding preparation, (ii) – (v) rice sprinkle powder, bouillon cube, instant cocoa drink, and snack bar, respectively with low leucine for IVA; low valine, isoleucine, methionine and threonine for PA and MMA. Results: All five formulated products provide 500-600 kcal/100 g, adequate protein in which the offending amino acids were controlled at non-harmful levels. These products were shelf stable at room temperature (Aw = 0.3-0.5). Conclusion: The products that were formulated from fish maw and roasted sunflower kernel provide proteins of appropriate quality and quantity for long-term management of branched-chain organic acidurias. The developed products should be further tested for efficacy among patients in accordance with an adequately powered study design.
ABSTRACT
La determinación de aminoácidos en sangre, es una prueba fundamental en la detección de errores hereditarios de la degradación de algunos aminoácidos y algunas acidurias orgánicas. El objetivo del presente trabajo, ha sido establecer valores de referencia para aminoácidos en sangre de caninos adultos mediante espectrometría de masas en tándem. Fueron obtenidas muestras de sangre de 60 caninos normales mayores de 18 meses (30 machos y 30 hembras). Las muestras fueron tomadas en papel de filtro y analizadas mediante espectrometría de masas en tándem. No fue encontrada diferencia significativa entre machos y hembras. Son reportados valores de referencia en caninos usando esta técnica. La espectrometría de masas en tándem constituye una herramienta importante para el diagnóstico de metabolopatías.
The measurement of blood amino acids is a basic test for the detection of inherited inborn errors related to some amino acids metabolism and organic acidurias. The objective of the present study was to establish reference values for amino acids in blood of canines using tandem mass spectrometry. Blood samples from 60 normal canines over 18 moths of age (30 male and 30 female) were obtained, and dried blood spots were prepared for amino acids analysis by tandem mass spectrometry. No significant differences between sexes were found. Reference values for amino acids in canines using this technique are provided. Tandem mass spectrometry is an important tool for the diagnosis of metabolic disorders.