Context Ketogenic diet has recently made a comeback as a part of lifestyle and dietary modifications in patients with polycystic ovary syndrome (PCOS). Despite studies suggesting its beneficial effects in reversing hormonal imbalance in women with PCOS, evidence has been patchy and derived from small populations under varying conditions. Objective To pool evidence from clinical trials to study the effects of ketogenic diet on reproductive hormones (LH/FSH ratio, free testosterone, serum progesterone) and observe evidence of weight change. Methods PubMed, ScienceDirect, Scopus, and Web of Science core collection were searched for clinical trials evaluating the effects of ketogenic diet in established PCOS women consistent with the Rotterdam classification. Single- or double-arm studies that included an outcome of interest were included. Two investigators worked independently to screen potential articles and a designated investigator extracted data on study characteristics and evaluated the outcomes. Data were pooled using a random-effects model. The quality of selected studies was assessed using the Cochrane Risk of Bias Tool. Results Following ≥45 days of intervention with ketogenic diet among women with PCOS, significant improvement was observed in reproductive hormone levels, with reduced LH/FSH ratio (d −0.851; 95% CI −1.015, −0.686; P < .001), reduced serum free testosterone (d −0.223; 95% CI −0.328, −0.119; P < .001), and an increased in serum sex hormone binding globulin (SHBG) (d 9.086; 95% CI 3.379, 14.792; P = .002). Significant weight loss was unanimously observed in all included studies (d −11.56; 95% CI −14.97, −8.15; P < .001). Conclusion Short-term ketogenic diet potentially improved hormonal imbalances commonly associated with PCOS.

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. 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. 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. 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.

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.

Chronic kidney disease (CKD) is a progressive disease in which accurate estimation of glomerular filtration rate (GFR) is essential for staging and guiding therapy. Serum creatinine is widely used but influenced by non-renal factors, while cystatin C and β2-microglobulin (β2M) may provide complementary information related to filtration and tubular or inflammatory factors. This study compared the discriminatory performance of creatinine, cystatin C and β2M for separating CKD stage 3 from stage 4 within the 2021 CKD-EPI eGFR framework in 45 adults with CKD stages 3–4. CKD stage classification was defined using the 2021 CKD-EPI creatinine and creatinine–cystatin C equations (eGFRcr, eGFRcr–cys) with a threshold of 30 mL/min/1.73 m². Receiver operating characteristic (ROC) analysis evaluated each marker’s ability to distinguish moderate from severe CKD. Creatinine showed high diagnostic accuracy (AUC up to 0.98). Cystatin C achieved 100% specificity at the optimal cut-off for severe CKD and showed comparable diagnostic accuracy to creatinine under the eGFRcr–cys framework (AUC 0.978 vs. 0.957). β2M demonstrated AUCs up to 0.97, with sensitivity and specificity above 90%. These findings support a multi-marker evaluation within the 2021 CKD-EPI-based staging, rather than validation against measured GFR. Larger studies incorporating measured GFR and relevant clinical confounders are warranted.

Background. Newborn screening in Malaysia includes congenital hypothyroidism and glucose-6-phosphate dehydrogenase deficiency. Screening for inborn errors of metabolism (IEM) is typically offered only for symptomatic patients. Objective. This study aimed to review the clinical and biochemical characteristics of children who experienced early mortality because of IEM. Methods. Malaysian children who were diagnosed with IEM and died before 5 years of age, were identified through selective screening of 36 467 at-risk patients between January 2015 and December 2021. Results. Thirty-six cases were detected. The mortality rate of children under 5 years diagnosed with IEM was 1.4 per 10 000 population. Clinical symptoms overlapped across the different IEM groups, and notably, similar organic compounds were found in different types of IEM. Conclusions. The mortality rate due to IEM is significant in Malaysia and most mortalities occurring during the neonatal period.

Background: Congenital disorders of glycosylation (CDG) are rare inborn errors of metabolism with multisystemic manifestations. SSR4-CDG is an ultra-rare X-linked subtype caused by pathogenic variants in SSR4, a component of the translocon-associated protein (TRAP) complex essential for protein translocation and N-glycosylation. Case presentation: We report a two-year-old Malaysian male presenting with global developmental delay, central hypotonia, microcephaly with complete agenesis of the corpus callosum, recurrent infections, bilateral vesicoureteral reflux, and failure to thrive. Growth parameters (weight, length, and head circumference) were persistently below the expected percentiles, indicating postnatal growth restriction. Initial metabolic and biochemical investigations for global developmental delay were unremarkable, apart from mild hyperammonemia. Transferrin isoform analysis demonstrated a type I CDG pattern, raising suspicion of a glycosylation defect. Results: Transferrin glycopeptide LC–MS/MS showed impaired N-glycan occupancy at both glycosylation sites (Asn432 and Asn630), with reduced fully sialylated glycoforms and increased non-glycosylated peptides. Targeted metabolomics using triple quadrupole LC–MS/MS revealed systemic abnormalities, including elevated arginine and phenylalanine, reduced glutamate, increased lysophosphatidylcholine (C24:0-LPC), and generalized depletion of free and acylcarnitines. Whole-exome sequencing identified a novel hemizygous SSR4 variant (c.98del; p.Pro33LeufsTer23) on the X chromosome, predicted to produce a truncated, nonfunctional protein. Conclusions: This is the first Malaysian patient with SSR4-CDG, comprehensively characterized using a multi-omics diagnostic workflow. The integration of glycoproteomics, metabolomics, and exome sequencing provided a detailed biochemical fingerprint that expands the clinical, genetic, and metabolic spectrum of SSR4-CDG and demonstrates the diagnostic and translational value of multi-omics approaches in inborn errors of metabolism.