Scholars@Duke
Ashlee R. Stiles

Ashlee R. Stiles

Associate Professor of Pediatrics
Pediatrics, Medical Genetics
ashlee.stiles@duke.edu
801-6 Capitola Dr, Durham, NC 27713
801-6 Capitola Drive, Durham, NC 27713

Selected Publications

Critical sample collection delayed? Urine organic acid analysis can still save the day! A new case of HMG-CoA synthase deficiency.

Journal Article Mol Genet Metab Rep · March 2024 Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (mHS) deficiency is an autosomal recessive disorder of ketone body synthesis caused by biallelic pathogenic variants in HMGCS2. Clinical symptoms are precipitated by prolonged fasting and/or i ... Full text Link to item Cite

Biomarker testing for lysosomal diseases: A technical standard of the American College of Medical Genetics and Genomics (ACMG)

Journal Article Genetics in Medicine · January 1, 2024 Measurement of lysosomal disease (LD) biomarkers can reveal valuable information about disease status. Lyso-globotriaosylceramide (lyso-Gb3), glucosylsphingosine (lyso-Gb1), galactosylsphingosine (psychosine), and glucose tetrasaccharide (Glca1-6Glca1-4Glc ... Full text Cite

Rescue of glutaric aciduria type I in mice by liver-directed therapies.

Journal Article Sci Transl Med · April 19, 2023 Glutaric aciduria type I (GA-1) is an inborn error of metabolism with a severe neurological phenotype caused by the deficiency of glutaryl-coenzyme A dehydrogenase (GCDH), the last enzyme of lysine catabolism. Current literature suggests that toxic catabol ... Full text Link to item Cite

RESCUE OF GLUTARIC ACIDURIA TYPE I MICE BY LIVER DIRECTED THERAPIES

Conference Molecular Genetics and Metabolism · March 2023 Full text Cite

Glucosylsphingosine (Lyso-Gb1): An Informative Biomarker in the Clinical Monitoring of Patients with Gaucher Disease.

Journal Article Int J Mol Sci · November 29, 2022 Historically, disease burden and treatment responses in patients with Gaucher disease (GD) was assessed by monitoring clinical data, laboratory, imaging, chitotriosidase (CHITO), and other biomarkers; however, these biomarkers lack specificity and CHITO is ... Full text Open Access Link to item Cite

The role of glucosylsphingosine as an early indicator of disease progression in early symptomatic type 1 Gaucher disease.

Journal Article Mol Genet Metab Rep · June 2021 Gaucher disease (GD), a lysosomal storage disorder caused by β-glucocerebrosidase deficiency, results in the accumulation of glucosylceramide and glucosylsphingosine. Glucosylsphingosine has emerged as a sensitive and specific biomarker for GD and treatmen ... Full text Open Access Link to item Cite

Combined analysis of plasma or serum glucosylsphingosine and globotriaosylsphingosine by UPLC-MS/MS.

Journal Article Clin Chim Acta · December 2020 PURPOSE: To develop a method for the combined analysis of plasma and serum glucosylsphingosine (lyso-Gb1) and globotriaosylsphingosine (lyso-Gb3), biomarkers of Gaucher disease (GD) and Fabry disease (FD), respectively. METHODS: Internal standards were add ... Full text Link to item Cite

Comparison of dermatan sulfate and heparan sulfate concentrations in serum, cerebrospinal fluid and urine in patients with mucopolysaccharidosis type I receiving intravenous and intrathecal enzyme replacement therapy.

Journal Article Clin Chim Acta · September 2020 AIMS: To validate a liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the measurement of glycosaminoglycans (GAGs) in plasma and serum. To establish plasma, cerebrospinal fluid (CSF) and urine reference intervals. To compare GAGs in se ... Full text Link to item Cite

A comprehensive testing algorithm for the diagnosis of Fabry disease in males and females.

Journal Article Mol Genet Metab · July 2020 PURPOSE: Successful diagnosis of Fabry disease is often delayed or missed in patients, especially females, due to clinical heterogeneity and a lack of disease awareness. We present our experience testing for Fabry disease in high risk populations and discu ... Full text Link to item Cite

Quantification of glucosylsphingosine in plasma/serum by UPLC-MS/MS

Conference Molecular Genetics and Metabolism · February 2019 Full text Cite

Plasma lyso-Gb3 as a diagnostic marker for Fabry disease

Conference Molecular Genetics and Metabolism · February 2018 Full text Cite

Mutations in TFAM, encoding mitochondrial transcription factor A, cause neonatal liver failure associated with mtDNA depletion.

Journal Article Mol Genet Metab · September 2016 In humans, mitochondrial DNA (mtDNA) depletion syndromes are a group of genetically and clinically heterogeneous autosomal recessive disorders that arise as a consequence of defects in mtDNA replication or nucleotide synthesis. Clinical manifestations are ... Full text Link to item Cite

New cases of DHTKD1 mutations in patients with 2-ketoadipic aciduria

Journal Article · January 1, 2016 2-Ketoadipic aciduria (OMIM 204750), a defect in the catabolic pathway of tryptophan, lysine, and hydroxylysine, is characterized by elevations in 2-ketoadipic, 2-aminoadipic, and 2-hydroxyadipic acids. Patients with the aforementioned biochemical profile ... Full text Cite

Successful diagnosis of HIBCH deficiency from exome sequencing and positive retrospective analysis of newborn screening cards in two siblings presenting with Leigh's disease.

Journal Article Mol Genet Metab · August 2015 PURPOSE: 3-Hydroxyisobutryl-CoA hydrolase (HIBCH) deficiency is a rare disorder of valine metabolism. We present a family with the oldest reported subjects with HIBCH deficiency and provide support that HIBCH deficiency should be included in the differenti ... Full text Link to item Cite

Genetic, anatomic, and clinical determinants of human serum sterol and vitamin D levels.

Journal Article Proc Natl Acad Sci U S A · September 23, 2014 An unknown fraction of the genome participates in the metabolism of sterols and vitamin D, two classes of lipids with diverse physiological and pathophysiological roles. Here, we used mass spectrometry to measure the abundance of >60 sterol and vitamin D d ... Full text Link to item Cite

A comprehensive method for extraction and quantitative analysis of sterols and secosteroids from human plasma.

Journal Article J Lipid Res · July 2012 We describe the development of a method for the extraction and analysis of 62 sterols, oxysterols, and secosteroids from human plasma using a combination of HPLC-MS and GC-MS. Deuterated standards are added to 200 μl of human plasma. Bulk lipids are extrac ... Full text Link to item Cite

SRD5A3: A Surprising Role in Glycosylation

Journal Article Cell · January 1, 2010 The steroid 5α-reductase (SRD5A) family of enzymes produces steroid hormones that regulate male sexual development. Now, Cantagrel et al. (2010) identify a member of this family, SRD5A3, as a polyprenol reductase with a crucial role in N-linked protein gly ... Full text Cite

CYP7B1: one cytochrome P450, two human genetic diseases, and multiple physiological functions.

Journal Article J Biol Chem · October 16, 2009 The CYP7B1 cytochrome P450 enzyme hydroxylates carbons 6 and 7 of the B ring of oxysterols and steroids. Hydroxylation reduces the biological activity of these substrates and facilitates their conversion to end products that are readily excreted from the b ... Full text Link to item Cite