Background Glycosaminoglycans in urine (U-GAG) are diagnostic biomarkers of mucopolysaccharidoses (MPS). How renal dysfunction influences U-GAG/creatinine (crn) ratio in children with chronic kidney disease (CKD) has been scarcely studied. We investigated the influence of glomerular filtration rate (GFR) on U-GAG/crn ratio, and assessed the effect of age, sex, and urine dipstick markers indicating kidney disease (protein, blood, glucose and leukocytes). Methods We examined 96 children (age range 0.25–17.5 years) with CKD. GFR was measured by iohexol clearance using seven time-point blood samples (range GFR 6.3–153 mL/min/1.73m2). U-GAG was measured by a dimethyl-methylene blue (DMB) assay. The reference cohort was samples from the laboratory production from 2017 to 2022 (n = 10,165). Age-adjustment of U-GAG/crn ratio was done after appropriate transformation and regression analysis. The influence of GFR, total urine protein-to-crn ratio (U-PCR), age, sex, and urine dipstick markers on U-GAG/crn ratio were examined through z-scores. Results With correction for U-PCR, GFR correlated positively with U-GAG/crn ratio (p < 0.001), with an effect size of relevance for diagnostic interpretation. Urine blood and glucose was associated with elevated U-GAG/crn ratios, and the U-GAG/crn ratio showed a statistically significant age–sex interaction at the onset of puberty (p < 0.001). Conclusion GFR, U-PCR, age and sex are significant covariates of U-GAG/crn ratio and should be assessed if U-GAG/crn ratio does not fit the clinical picture. Reduced GFR may be associated with an increased risk of false negative MPS screening, while increased U-PCR may be associated with false positive MPS screenings. Synopsis GFR influences glycosaminoglycans in urine.
CPT1A encodes carnitine palmitoyltransferase 1A (CPT1A), a crucial rate-limiting enzyme in fatty acid metabolism. Facilitating the mitochondrial transport of long-chain fatty acids for β-oxidation, acetyl-CoA and ketone bodies are produced for subsequent ATP production. This process is vital during periods of low glucose availability, such as overnight fasting or strenuous exercise, when the body experiences high energy demands.Because CPT1A is widely expressed in various tissues, CPT1A variants that affect CPT1A enzymatic activity can lead to a wide spectrum of metabolic dysfunction and clinical manifestations. Among the CPT1A variants that alter CPT1A functional dynamics, CPT1A p.P479L is one of the most notable variants.The CPT1A c.1436C>T p.P479L (rs80356779) is a unique variant that is highly prevalent in Indigenous populations of northern Canada, coastal British Columbia, Alaska and Greenland. Its high frequency in these populations may be attributed to positive selection, conferring an adaptive advantage in Arctic regions and coastal British Columbia. However, under certain conditions and in combination with other genetic factors, CPT1A p.P479L may also contribute to health risks, highlighting its dual nature as both an adaptive survival trait and a potential health concern. This paradox has garnered increasing attention in both scientific and medical fields. While research on CPT1A p.P479L has gradually been increasing over the past two decades, a comprehensive review of current research findings is still lacking. This review article aims to summarize the state of research on the CPT1A p.P479L variant, explore its health implications, and discuss future research directions.
