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
OBJECTIVE: Carnitine-acylcarnitine Translocase (CACT) deficiency (OMIM 212138) and carnitine palmitoyl transferase 2 (CPT2) deficiency (OMIM 60065050) are rare inherited disorders of mitochondrial long chain fatty acid oxidation. The aim of our study is to review the clinical, biochemical and molecular characteristics in children diagnosed with CACT and CPT2 deficiencies in Malaysia. DESIGN AND METHODS: This is a retrospective study. We reviewed medical records of six patients diagnosed with CACT and CPT2 deficiencies. They were identified from a selective high-risk screening of 50,579 patients from January 2010 until Jun 2020. RESULTS: All six patients had either elevation of the long chain acylcarnitines and/or an elevated (C16 + C18:1)/C2 acylcarnitine ratio. SLC25A20 gene sequencing of patient 1 and 6 showed a homozygous splice site mutation at c.199-10 T > G in intron 2. Two novel mutations at c.109C > T p. (Arg37*) in exon 2 and at c.706C > T p. (Arg236*) in exon 7 of SLC25A20 gene were found in patient 2. Patient 3 and 4 (siblings) exhibited a compound heterozygous mutation at c.638A > G p. (Asp213Gly) and novel mutation c.1073 T > G p. (Leu358Arg) in exon 4 of CPT2 gene. A significant combined prevalence at 0.01% of CACT and CPT2 deficiencies was found in the symptomatic Malaysian patients. CONCLUSIONS: The use of the (C16 + C18:1)/C2 acylcarnitine ratio in dried blood spot in our experience improves the diagnostic specificity for CACT/CPT2 deficiencies over long chain acylcarnitine (C16 and C18:1) alone. DNA sequencing for both genes aids in confirming the diagnosis.