三頭酵素欠損症

BACKGROUND AND OBJECTIVE: Congenital and developmental disorders should be detected early to avoid complications such as disability and death. The Philippine clinical practice guidelines (CPG) were developed to guide healthcare professionals on screening for congenital and developmental disorders among apparently healthy neonates and children. METHODS: Following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to CPG development recommended by the Department of Health (DOH), the steering committee, composed of clinical geneticists, developmental pediatricians, family and community medicine physicians, and ambulatory and community pediatricians, set the objectives of the CPG and formulated clinical questions in consultation with stakeholders. There were 15 priority guideline questions that covered various disorders including inborn errors of metabolism, critical congenital heart disease, developmental delay, learning disabilities, and autism. Evidence review experts systematically reviewed existing clinical practice guidelines, appraised, and summarized the evidence. A multisectoral panel formulated recommendations through a formal consensus based on the evidence summaries. The CPG was externally reviewed prior to publication. RESULTS: The CPG provides twenty (20) recommendations on fifteen (15) prioritized questions in the screening for certain congenital and developmental disorders. This CPG contains recommendations for the screening for critical congenital heart disease, thalassemia, Glucose-6-phosphate dehydrogenase (G6PD) deficiency, developmental delay, and autism spectrum disorder. Recommendations against routine screening of cystic fibrosis, sickle cell disease, methionine adenosyltransferase deficiency, tyrosinemia, long chain 3-hydroxy acyl CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MTPD), carnitine palmitoyl transferase types 1 and 2 (CPT1, CPT2) and glutaric aciduria type 2 (GA2), biotidinase deficiency, beta-ketothiolase deficiency, holocarboxylase synthetase deficiency, and isovaleric acidemia were made. CONCLUSION: The consensus panel recommended the screening of certain conditions, based on the available evidence, the burden of disease, the cost of the confirmatory testing, and its applicability to the population. Although this CPG intends to influence the direction of health policies for the general population, it should not be the sole basis for recreating or abolishing practices that aim to improve the health conditions of many Filipinos, particularly those part of the workforce.

BACKGROUND: Patients with LCHADD/TFPD are counseled to follow a diet low in long-chain fats (LCT) and supplement with medium-chain fats (MCT) with adequate micronutrients, but there is limited data on patient implementation of recommendations. We analyzed diet intake of LCHADD/TFPD participants twice, 2 years apart. METHODS: Participants enrolled in the longitudinal Natural History of LCHAD Retinopathy study completed a 3-day food record and supplement logs at baseline and 2 years later. Differences in %LCT and MCT intake over time, and intra-individual and population variation, were analyzed. Percentage of participants meeting estimated average requirements (EAR) for fat-soluble (A, D, E, K) and water-soluble vitamins (B1, B2, B3, C) were calculated. RESULTS: Forty participants were enrolled, 2-36 years (48% female), 25% G1528C homozygous, 68% G1528C heterozygous, and 7% TFPD. Thirty-five baseline and 38 follow-up diet records were included. Fat intake was consistent over time; baseline 13.7% LCT, 18.8% MCT, follow-up 14.7% LCT, 20.6% MCT. Intra-individual variation ranged from 22% to 32% for MCT and LCT, respectively, but both were less than the overall population variation 49% MCT and 36% LCT. An average of 38.8% of participants took a multivitamin; however, only 51% met the EAR for fat-soluble vitamins compared to 81% for water-soluble vitamins. CONCLUSIONS: LCHADD/TFPD patients are consistently consuming a low-fat diet with appropriate supplementation of MCT. Day-to-day variation in %LCT was comparable to the general population, but absolute amount of fat was lower. A greater proportion of patients are still not meeting EAR for fat-soluble vitamins compared to water-soluble vitamins.

OBJECTIVES: MR neurography (MRN) is a modern technique for visualizing peripheral nerves and quantifying microstructural pathology, yet its use in pediatric populations remains largely unexplored. This study evaluates the applicability and diagnostic performance of MRN in children and adolescents with genetically confirmed long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MTPD), in which peripheral neuropathy is a known long-term complication. MATERIALS AND METHODS: In a prospective cross-sectional study, 15 patients (LCHADD n = 6; MTPD n = 9) and 14 age-matched controls underwent high-resolution mid-thigh MRN of the sciatic nerve to assess (1) T2-based lesion burden for tibial (SNTib) and peroneal (SNPer) fascicles, (2) functional nerve integrity of the tibial fascicles using diffusion tensor metrics, including fractional anisotropy (FA) and radial diffusivity (RD), and (3) tibial fascicle-based T2 relaxometry parameters. In addition, clinical and electrophysiological data were obtained. Age-adjusted linear regression, ROC analyses, and linear discriminant analyses (LDA) quantified group effects and classification performance. RESULTS: Overall, patients showed higher T2 lesion burden compared with controls (SNTib: +2.75%, P = 0.001; SNPer: +1.94%, P = 0.001), reduced tibial fascicle FA (Δ: -0.098, P = 0.001), and increased tibial fascicle RD (Δ: +147.4×10-6 mm2/s, P = 0.011). Subgroup comparisons between LCHADD and MTPD revealed no significant differences. Of the 15 patients, 7 exhibited signs of clinical neuropathy. Neuropathic individuals showed pronounced abnormalities (SNTib: +4.22%, P < 0.001; SNPer: +2.29%, P = 0.002; ΔFA: -0.138, P < 0.001), while even those without clinical neuropathy exhibited elevated SNPer lesion burden (+1.64%; P = 0.018) and reduced tibial fascicle FA (Δ: -0.062, P = 0.03), compared with controls, indicating subclinical involvement. SNTib lesion burden showed excellent discrimination (AUC: 95.2%), and FA performed well (AUC: 81.2%). Multiparametric LDA achieved 93% apparent in-sample accuracy for patients versus controls, 86% for LCHADD versus MTPD, and 90% for classifying neuropathic, non-neuropathic, and control groups. CONCLUSIONS: MRN can be readily applied in children and adolescents and sensitively detects both clinically manifest and subclinical peripheral nerve involvement in long-chain fatty acid oxidation disorders. Extending this capability, exploratory LDA suggests that combining multiple MRN metrics may provide complementary diagnostic and phenotypic information beyond individual parameters.

Long-chain fatty acid oxidation disorders (lcFAODs) are genetic disorders of energy metabolism that are associated with a risk of metabolic decompensation, especially during catabolic episodes. With improvement in diagnostics and treatment, more women with lcFAODs now reach child-bearing age. So far, little is known about the risk and outcome of pregnancies, particularly in women with more severe forms of lcFAODs. We performed an international web-based survey among health care professionals involved in the care of individuals with lcFAODs and collected data on 89 pregnancies in 39 women (mild VLCAD deficiency n = 8, severe VLCAD deficiency n = 10, LCHAD deficiency n = 4, CPT2 deficiency n = 14, CPT1 deficiency n = 3). There were 72 live births, 12 spontaneous miscarriages, and one stillbirth at 41 weeks of gestation. Four women were still pregnant at the time of the survey. In 25 women, the diagnosis was known before the first pregnancy, whereas 14 had at least one pregnancy before diagnosis. Most women remained metabolically stable during pregnancy, although 19% of women had at least one metabolic decompensation during pregnancy. Forty-one percent of babies were delivered by spontaneous vaginal delivery, 33% after induced labor, and 19% by an elective Caesarean section. Most deliveries were uncomplicated, with preventive i.v. glucose infusions given in 50%. However, 21% of mothers developed a metabolic decompensation in the postpartum period. No maternal deaths were reported. In conclusion, our data show that the outcome of pregnancies in lcFAOD patients is generally favorable, despite a significant risk of metabolic decompensation during the postpartum period.