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Normal reference ranges for urinary ?-aminolevulinic acid and porphobilinogen levels.

ABSTRACT: Acute hepatic porphyria (AHP) is a family of rare, serious, and potentially life-threatening metabolic disorders caused by mutations in genes encoding enzymes involved in hepatic heme biosynthesis. AHP is characterized by accumulation of neurotoxic heme intermediates, ?-aminolevulinic acid (ALA), and porphobilinogen (PBG), which are thought to be causal for the disease manifestations. Novel therapeutic treatments such as givosiran, an RNA interference therapeutic that was recently approved for treatment of adults with AHP, are focused on reducing the levels of ALA and PBG in patients toward levels observed in a healthy population. While there are two published reports on the distribution of urinary ALA and PBG levels in healthy subjects, these lacked the required details to enable the calculation of reference limits for ALA and PBG. Therefore, urinary ALA and PBG levels were quantified in 150 healthy subjects using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method that is highly sensitive, specific, accurate, and reproducible. These data were used to establish the upper limit of normal (ULN) values for ALA and PBG as 1.47 and 0.137?mmol/mol Cr, respectively. Relative to these ULN values, baseline urinary ALA and PBG levels in AHP patients were found to be 9.3- to 12-fold, and 238- to 336-fold higher, respectively. Results from this study can serve as a guide to assess the effectiveness of therapeutic interventions in lowering ALA and PBG.

SUBMITTER: Agarwal S

PROVIDER: S-EPMC7802627 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Normal reference ranges for urinary δ-aminolevulinic acid and porphobilinogen levels.

Agarwal Sagar S Habtemarium Bahru B Xu Yuanxin Y Simon Amy R AR Kim Jae B JB Robbie Gabriel J GJ

JIMD reports 20201001 1

Acute hepatic porphyria (AHP) is a family of rare, serious, and potentially life-threatening metabolic disorders caused by mutations in genes encoding enzymes involved in hepatic heme biosynthesis. AHP is characterized by accumulation of neurotoxic heme intermediates, δ-aminolevulinic acid (ALA), and porphobilinogen (PBG), which are thought to be causal for the disease manifestations. Novel therapeutic treatments such as givosiran, an RNA interference therapeutic that was recently approved for t ...[more]

PMID: 33473344

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Project description:BackgroundExposure to lead (Pb) affects multiple health outcomes and physiological systems. In adults, even small increases in blood Pb levels have been associated with decreased glomerular filtration rate, increased risk of hypertension and increased incidence of essential tremor. To date, there have been few Pb-exposure assessments using the United States Occupational Health and Safety Administration (OSHA) regulations.ObjectiveThe aim of the present study was to assess Pb-exposure in terms of elevated blood lead levels (BLL) and urinary-?-aminolevulinic acid (U-?-ALA) levels of workers exposed to Pb in the lead acid battery industry in Tamil Nadu, India based on Pb exposure regulations set by the American Conference of Governmental Industrial Hygienists (ACGIH) and OSHA.Materials and methodsBLLs and U-?-ALA were estimated in 449 male workers exposed to Pb across ten different job categories in a lead acid battery factory. Worker BLLs were estimated using atomic absorption spectrophotometry and U-?-ALA was estimated using spectrophotometry.ResultsThe Biological Exposure Index of the American Conference of Governmental Industrial Hygienists (BEI-ACGIH) were used to assess Pb exposure. BLLs <30 ?g/dL were found in 63.5% of workers, and 36.5% of workers had BLLs>30 ?g/dL. The present study also assessed Pb exposure using OSHA regulations and found that 83.3% of workers had BLLs <40 ?g/dL and 16.7% of workers had BLLs>40 ?g/dL. Among these workers, 0.7% of workers had BLLs >60 ?g/dL. An excessive excretion of U-?-ALA (20-40 mg/L) was noted in pasting area workers (2.6%) followed by executives (2.2%) and assembly workers (0.9%).ConclusionsWorkers in the job categories of pasting and assembly, as well as executives, are at high risk of Pb exposure compared to other job categories. We recommend placing humidifiers on the roof and keeping a water bath closer the to plate cutting area to reduce fugitive Pb dust emissions. We recommended workers with BLLs >60 ?g/dL be removed from jobs involving Pb exposure and return to work only when their BLLs are <40 ?g/dL.Participant consentObtained.Ethics approvalThe study was approved by the ethics committee of the Regional Occupational Health Centre (Southern) Bengaluru, part of the National Institute of Occupational Health of India.Competing interestsThe authors declare no competing financial interests.

Project description:AimsTo determine population-related and technical sources of variation in cardiac magnetic resonance (CMR) reference ranges for left ventricular (LV) quantification through a formal systematic review and meta-analysis.Methods and resultsThis study is registered with the International Prospective Register of Systematic Reviews (CRD42019147161). Relevant studies were identified through electronic searches and assessed by two independent reviewers based on predefined criteria. Fifteen studies comprising 2132 women and 1890 men aged 20-91 years are included in the analysis. Pooled LV reference ranges calculated using random effects meta-analysis with inverse variance weighting revealed significant differences by age, sex, and ethnicity. Men had larger LV volumes and higher LV mass than women [LV end-diastolic volume (mean difference = 6.1 mL/m2, P-value = 0.014), LV end-systolic volume (MD = 4 mL/m2, P-value = 0.033), LV mass (mean difference = 12 g/m2, P-value = 7.8 × 10-9)]. Younger individuals had larger LV end-diastolic volumes than older ages (20-40 years vs. ≥65 years: women MD = 14.0 mL/m2, men MD = 14.7 mL/m2). East Asians (Chinese, Korean, Singaporean-Chinese, n = 514) had lower LV mass than Caucasians (women: MD = 6.4 g/m2, P-value = 0.016; men: MD = 9.8 g/m2, P-value = 6.7 × 10-5). Between-study heterogeneity was high for all LV parameters despite stratification by population-related factors. Sensitivity analyses identified differences in contouring methodology, magnet strength, and post-processing software as potential sources of heterogeneity.ConclusionThere is significant variation between CMR normal reference ranges due to multiple population-related and technical factors. Whilst there is need for population-stratified reference ranges, limited sample sizes and technical heterogeneity precludes derivation of meaningful unified ranges from existing reports. Wider representation of different populations and standardization of image analysis is urgently needed to establish such reference distributions.

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Normal reference ranges for urinary ?-aminolevulinic acid and porphobilinogen levels.

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Normal reference ranges for urinary δ-aminolevulinic acid and porphobilinogen levels.

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