RESUMO
Clinical diagnosis of inborn errors of metabolism in the suspected patients is usually guided by the initial general investigations in the laboratory such as the concentration of ammonia, blood gases status, blood glucose and ketones. The establishment of a biochemical diagnosis in patients with inborn errors of metabolism depends on the detection of the specific metabolites in the abnormal metabolic pathway which can appear in any of the body fluids but are most commonly tested in blood and urine samples. Acylcarnitine and/or acylcarnitine ratio in patients with carnitine acylcarnitine translocase and carnitine palmitoyl transferase deficiency showed an abnormal profile regardless of the metabolic status of patients. The acylcarnitine was derived from the analysis of dried blood spot using multiple reaction monitoring (MRM) which was performed using quadrupole mass spectrometry. The dataset presented in this article was generated from analysis of acylcarnitines in the 17,121 dried blood spots from symptomatic Malaysian patients less than fifty years old who exhibited symptoms suggestive of inborn errors of metabolism, but had a normal acylcarnitine profile. A precursor or ion scan of m/z 85 was selected for the analysis. Quantification of each analyte was obtained using the signal intensity ratio of the acylcarnitine to its internal standard. The acylcarnitines analyzed included C0, C2, C3, C3DC, C4, C5, C5:1, C5DC, C5OH, C6, C8, C10, C12, C14, C16, C18, C18:1, C16OH, C18OH and C18:1OH and was analyzed using Neolynx V4.0 software. We decided to choose the 1st and 99th percentiles as the minimum and maximum cut-offs. The filtered part of data in this article was used in the article Novel mutations associated with Carnitine-Acylcarnitine Translocase and Carnitine Palmitoyl Transferase 2 deficiencies in Malaysia. This dataset is intended to enable the scientific communities to get access to the raw dataset for future translational research use in inborn errors of metabolism as very few acylcarnitine data was developed and published for the symptomatic patients suspected of inborn errors of metabolism especially in the Asian population.
RESUMO
BACKGROUND: The aim of this study was to determine the feasibility of performing newborn screening (NBS) of inborn errors of metabolism (IEMs) using tandem mass spectrometry (TMS) and the impact on its detection rate in Malaysia. METHODS: During the study period between June 2006 and December 2008, 30,247 newborns from 11 major public hospitals in Malaysia were screened for 27 inborn errors of amino acid, organic acid and fatty acid metabolism by TMS. Dried blood spot (DBS) samples were collected between 24 h and 7 days with parental consent. Samples with abnormal results were repeated and the babies were recalled to confirm the diagnosis with follow-up testing. RESULTS: Cut-off values for amino acids and acylcarnitines were established. Eight newborns were confirmed to have IEM: two newborns with Maple syrup urine disease (MSUD), two with methylmalonic aciduria (MMA) one with ethylmalonic aciduria, two with argininosuccinic aciduria and one with isovaleric aciduria. Diagnosis was missed in two newborns. The detection rate of IEMs in this study was one in 2916 newborns. The sensitivity and specificity of TMS were 80% and 99%, respectively. CONCLUSIONS: IEMs are common in Malaysia. NBS of IEMs by TMS is a valuable preventive strategy by enabling the diagnosis and early treatment of IEM before the onset of symptoms aiming at prevention of mental retardation and physical handicap. A number of shortcomings warrant further solution so that in near future NBS for IEMs will become a standard of care for all babies in Malaysia in tandem with the developed world.