Scholars@Duke
Sarah Phyllis Young

Sarah Phyllis Young

Professor of Pediatrics
Pediatrics, Medical Genetics
sarah.young@duke.edu
Box 103856, Durham, NC 27710
801 Capitola Drive, Suite 6, Durham, NC 27713

Selected Publications

Persistent elevations of alkaline phosphatase as an early indicator of GM1 gangliosidosis.

Journal Article Mol Genet Metab Rep · March 2025 GLB1-related disorders are autosomal recessive lysosomal diseases caused by enzymatic deficiency of β-galactosidase. Enzymatic deficiency of β-galactosidase may lead to one of two phenotypes, GM1 gangliosidosis or mucopolysaccharidosis IVB (MPS IVB). GM1 g ... Full text Open Access Link to item Cite

Quantification of Glycosaminoglycans in Urine by Isotope Dilution Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry.

Journal Article Curr Protoc · February 2025 Mucopolysaccharidoses (MPSs) are complex lysosomal diseases that result in the accumulation of glycosaminoglycans (GAGs) in urine, blood, and tissues. Lysosomal enzymes responsible for GAG degradation are defective in MPSs. GAGs including chondroitin sulfa ... Full text Link to item Cite

Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.

Journal Article Mol Psychiatry · January 7, 2025 A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher inc ... Full text Link to item Cite

College of American Pathologists (CAP)/American College of Medical Genetics and Genomics (ACMG) proficiency testing for urinary glycosaminoglycan analysis: A summary of performance.

Journal Article Genet Med Open · 2025 PURPOSE: Glycosaminoglycans (GAGs) accumulate in patients with mucopolysaccharidoses (MPS), multiple sulfatase deficiency, and mucolipidoses; measurement of total GAGs and the specific excretion pattern by fractionation can aid in their diagnosis. Since 19 ... Full text Link to item Cite

The attenuated hepatic clearance of propionate increases cardiac oxidative stress in propionic acidemia.

Journal Article Basic Res Cardiol · December 2024 Propionic acidemia (PA), arising from PCCA or PCCB variants, manifests as life-threatening cardiomyopathy and arrhythmias, with unclear pathophysiology. In this work, propionyl-CoA metabolism in rodent hearts and human pluripotent stem cell-derived cardiom ... Full text Link to item Cite

Progressive liver disease and dysregulated glycogen metabolism in murine GSD IX γ2 models human disease.

Journal Article Mol Genet Metab · December 2024 Hepatic glycogen storage disease type IX γ2 (GSD IX γ2) is a severe, liver-specific subtype of GSD IX. While all patients with hepatic GSD IX present with similar symptoms, over 95 % of patients with GSD IX γ2 progress to liver fibrosis and cirrhosis. Desp ... Full text Link to item Cite

Establishing a Core Outcome Set for Creatine Transporter Deficiency and Guanidinoacetate Methyltransferase Deficiency.

Journal Article medRxiv · September 10, 2024 Creatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies are rare inborn errors of creatine metabolism, resulting in cerebral creatine deficiency. Patients commonly exhibit intellectual and developmental disabilities, often acc ... Full text Link to item Cite

Whole exome sequencing reveals a dual diagnosis of BCAP31-related syndrome and glutaric aciduria III.

Journal Article Mol Genet Metab Rep · September 2024 BACKGROUND: Biochemical testing is a common first-tier approach in the setting of genetic evaluation of patients with unexplained developmental delay. However, results can be unclear, and a plan for second-tier analysis must be determined based on the pati ... Full text Link to item Cite

ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes.

Journal Article Mol Genet Metab · May 2024 Cerebral creatine deficiency syndromes (CCDS) are inherited metabolic phenotypes of creatine synthesis and transport. There are two enzyme deficiencies, guanidinoacetate methyltransferase (GAMT), encoded by GAMT and arginine-glycine amidinotransferase (AGA ... Full text Link to item Cite

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

Reduction of lysosome abundance and GAG accumulation after odiparcil treatment in MPS I and MPS VI models.

Journal Article Mol Genet Metab Rep · December 2023 Deficiencies of lysosomal enzymes responsible for the degradation of glycosaminoglycans (GAG) cause pathologies commonly known as the mucopolysaccharidoses (MPS). Each type of MPS is caused by a deficiency in a specific GAG-degrading enzyme and is characte ... Full text Link to item Cite

Intrauterine enzyme replacement therapies for lysosomal storage disorders: Current developments and promising future prospects.

Journal Article Prenat Diagn · December 2023 Lysosomal storage disorders (LSDs) are a group of monogenic condition, with many characterized by an enzyme deficiency leading to the accumulation of an undegraded substrate within the lysosomes. For those LSDs, postnatal enzyme replacement therapy (ERT) r ... Full text Link to item Cite

An exploratory study of plasma ceramides in comorbidities in Down syndrome.

Journal Article Am J Med Genet A · September 2023 Plasma ceramide levels (henceforth, "ceramides") are biomarkers of some diseases that are comorbidities of Down syndrome (DS). We sought to determine if comorbidities in DS were associated with ceramides, studying a convenience cohort of 35 study participa ... Full text Link to item Cite

In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe's Disease

Journal Article Obstetrical and Gynecological Survey · June 1, 2023 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

Quantification of Glycosaminoglycans in Urine by Isotope-Dilution Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry.

Journal Article Curr Protoc · March 2023 Mucopolysaccharidoses (MPSs) are complex lysosomal storage disorders that result in the accumulation of glycosaminoglycans (GAGs) in urine, blood, and tissues. Lysosomal enzymes responsible for GAG degradation are defective in MPSs. GAGs including chondroi ... Full text Link to item Cite

In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe's Disease.

Journal Article The New England journal of medicine · December 2022 Patients with early-onset lysosomal storage diseases are ideal candidates for prenatal therapy because organ damage starts in utero. We report the safety and efficacy results of in utero enzyme-replacement therapy (ERT) in a fetus with CRIM (cross-reactive ... Full text Cite

Cerebrospinal fluid amino acids glycine, serine, and threonine in nonketotic hyperglycinemia.

Journal Article Journal of inherited metabolic disease · July 2022 Nonketotic hyperglycinemia (NKH) is caused by deficient glycine cleavage enzyme activity and characterized by elevated brain glycine. Metabolism of glycine is connected enzymatically to serine through serine hydroxymethyltransferase and shares transporters ... Full text Cite

MPS VI associated ocular phenotypes in an MPS VI murine model and the therapeutic effects of odiparcil treatment.

Journal Article Mol Genet Metab · February 2022 Maroteaux - Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is a lysosomal storage disease resulting from insufficient enzymatic activity for degradation of the specific glycosaminoglycans (GAG) chondroitin sulphate (CS) and dermatan sulphate (DS). A ... Full text Link to item Cite

A retrospective longitudinal study and comprehensive review of adult patients with glycogen storage disease type III.

Journal Article Molecular genetics and metabolism reports · December 2021 IntroductionA deficiency of glycogen debrancher enzyme in patients with glycogen storage disease type III (GSD III) manifests with hepatic, cardiac, and muscle involvement in the most common subtype (type a), or with only hepatic involvement in pa ... Full text Open Access Cite

Multidimensional predictors of antidepressant responses: Integrating mitochondrial, genetic, metabolic and environmental factors with clinical outcomes.

Journal Article Neurobiology of stress · November 2021 Major depressive disorder (MDD) is a primary psychiatric illness worldwide; there is a dearth of new mechanistic models for the development of better therapeutic strategies. Although we continue to discover individual biological factors, a major challenge ... Full text Cite

Characterization of liver GSD IX γ2 pathophysiology in a novel Phkg2-/- mouse model.

Journal Article Molecular genetics and metabolism · July 2021 IntroductionLiver Glycogen Storage Disease IX is a rare metabolic disorder of glycogen metabolism caused by deficiency of the phosphorylase kinase enzyme (PhK). Variants in the PHKG2 gene, encoding the liver-specific catalytic γ2 subunit of PhK, a ... Full text Open Access Cite

A glutaminase isoform switch drives therapeutic resistance and disease progression of prostate cancer.

Journal Article Proc Natl Acad Sci U S A · March 30, 2021 Cellular metabolism in cancer is significantly altered to support the uncontrolled tumor growth. How metabolic alterations contribute to hormonal therapy resistance and disease progression in prostate cancer (PCa) remains poorly understood. Here we report ... Full text Link to item Cite

Diurnal variability of glucose tetrasaccharide (Glc4) excretion in patients with glycogen storage disease type III.

Journal Article JIMD Rep · March 2021 AIM: The urinary glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc (Glc4), is a glycogen limit dextrin that is elevated in patients with glycogen storage disease (GSD) type III. We evaluated the potential of uncooked cornstarch therapy to interfere with Gl ... Full text Link to item Cite

Laboratory analysis of acylcarnitines, 2020 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG).

Journal Article Genet Med · February 2021 Acylcarnitine analysis is a useful test for identifying patients with inborn errors of mitochondrial fatty acid β-oxidation and certain organic acidemias. Plasma is routinely used in the diagnostic workup of symptomatic patients. Urine analysis of targeted ... Full text 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

Response to Heiner-Fokkema et al.

Journal Article Genet Med · November 2020 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 Clinica chimica acta; international journal of clinical chemistry · September 2020 AimsTo 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 GAG ... Full text 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

Comparisons of Infant and Adult Mice Reveal Age Effects for Liver Depot Gene Therapy in Pompe Disease.

Journal Article Mol Ther Methods Clin Dev · June 12, 2020 Pompe disease is caused by the deficiency of lysosomal acid α-glucosidase (GAA). It is expected that gene therapy to replace GAA with adeno-associated virus (AAV) vectors will be less effective early in life because of the rapid loss of vector genomes. AAV ... Full text Open Access Link to item Cite

Higher dosing of alglucosidase alfa improves outcomes in children with Pompe disease: a clinical study and review of the literature.

Journal Article Genet Med · May 2020 PURPOSE: Enzyme replacement therapy (ERT) with recombinant human acid-α glucosidase (rhGAA) at standard dose of 20 mg/kg every other week is insufficient to halt the long-term progression of myopathy in Pompe disease. METHODS: We conducted a retrospective ... Full text Open Access Link to item Cite

Urine gastrin-releasing peptide in the first week correlates with bronchopulmonary dysplasia and post-prematurity respiratory disease.

Journal Article Pediatr Pulmonol · April 2020 RATIONALE: Bronchopulmonary dysplasia (BPD) is associated with post-prematurity respiratory disease (PRD) in survivors of extreme preterm birth. Identifying early biomarkers that correlate with later development of BPD and PRD may provide insights for inte ... Full text Link to item Cite

Improved muscle function in a phase I/II clinical trial of albuterol in Pompe disease.

Journal Article Mol Genet Metab · February 2020 This 24-week, Phase I/II, double-blind, randomized, placebo-controlled study investigated the safety and efficacy of extended-release albuterol in late-onset Pompe disease stably treated with enzyme replacement therapy at the standard dose for 4.9 (1.0-9.4 ... Full text Open Access Link to item Cite

Intrathecal enzyme replacement for cognitive decline in mucopolysaccharidosis type I, a randomized, open-label, controlled pilot study.

Journal Article Mol Genet Metab · February 2020 Central nervous system manifestations of mucopolysaccharidosis type I (MPS I) such as cognitive impairment, hydrocephalus, and spinal cord compression are inadequately treated by intravenously-administered enzyme replacement therapy with laronidase (recomb ... Full text Link to item Cite

Fenofibrate rapidly decreases hepatic lipid and glycogen storage in neonatal mice with glycogen storage disease type Ia.

Journal Article Hum Mol Genet · January 15, 2020 Glycogen storage disease type Ia (GSD Ia) is caused by autosomal mutations in glucose-6-phosphatase α catalytic subunit (G6PC) and can present with severe hypoglycemia, lactic acidosis and hypertriglyceridemia. In both children and adults with GSD Ia, ther ... Full text Link to item Cite

Evaluation of X-Linked Adrenoleukodystrophy Newborn Screening in North Carolina.

Journal Article JAMA Netw Open · January 3, 2020 IMPORTANCE: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal genetic disorder in which an accumulation of very long-chain fatty acids leads to inflammatory demyelination in the central nervous system and to adrenal cortex atrophy. In 2016, X-ALD was ... Full text Link to item Cite

Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring.

Journal Article Genet Med · December 2019 PURPOSE: In glycogen storage disease type III (GSD III), liver aminotransferases tend to normalize with age giving an impression that hepatic manifestations improve with age. However, despite dietary treatment, long-term liver complications emerge. We pres ... Full text Link to item Cite

Glycocalyx breakdown is increased in African children with cerebral and uncomplicated falciparum malaria.

Journal Article FASEB J · December 2019 Cerebral malaria (CM) from Plasmodium falciparum infection is associated with endothelial dysfunction and parasite sequestration. The glycocalyx (GCX), a carbohydrate-rich layer lining the endothelium, is crucial in vascular homeostasis. To evaluate the ro ... Full text Link to item Cite

Glycocalyx Breakdown Is Associated With Severe Disease and Fatal Outcome in Plasmodium falciparum Malaria.

Journal Article Clin Infect Dis · October 30, 2019 BACKGROUND: Interactions between the endothelium and infected erythrocytes play a major role in the pathogenesis of falciparum malaria, with microvascular dysfunction and parasite sequestration associated with worsening outcomes. The glycocalyx is a carboh ... Full text Link to item Cite

The North Carolina Experience with Mucopolysaccharidosis Type I Newborn Screening.

Journal Article J Pediatr · August 2019 OBJECTIVE: To evaluate the performance of a 2-tiered newborn screening method for mucopolysaccharidosis type I (MPS I) in North Carolina. STUDY DESIGN: The screening algorithm included a flow injection analysis-tandem mass spectrometry assay as a first-tie ... Full text Link to item Cite

Bezafibrate Enhances AAV Vector-Mediated Genome Editing in Glycogen Storage Disease Type Ia.

Journal Article Mol Ther Methods Clin Dev · June 14, 2019 Glycogen storage disease type Ia (GSD Ia) is a rare inherited disease caused by mutations in the glucose-6-phosphatase (G6Pase) catalytic subunit gene (G6PC). Absence of G6Pase causes life-threatening hypoglycemia and long-term complications because of the ... Full text Open Access Link to item Cite

Biomarkers of oxidative stress, inflammation, and vascular dysfunction in inherited cystathionine β-synthase deficient homocystinuria and the impact of taurine treatment in a phase 1/2 human clinical trial.

Journal Article J Inherit Metab Dis · May 2019 STUDY OBJECTIVE: A phase 1/2 clinical trial was performed in individuals with cystathionine β synthase (CBS) deficient homocystinuria with aims to: (a) assess pharmacokinetics and safety of taurine therapy, (b) evaluate oxidative stress, inflammation, and ... Full text Link to item Cite

Kinetic and Cross-Sectional Studies on the Genesis of Hypoargininemia in Severe Pediatric Plasmodium falciparum Malaria.

Journal Article Infect Immun · April 2019 The low bioavailability of nitric oxide (NO) and its precursor, arginine, contributes to the microvascular pathophysiology of severe falciparum malaria. To better characterize the mechanisms underlying hypoargininemia in severe malaria, we measured the pla ... Full text Link to item Cite

Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia.

Journal Article Hum Mol Genet · January 1, 2019 Glucose-6-phosphatase α (G6Pase) deficiency, also known as von Gierke's Disease or Glycogen storage disease type Ia (GSD Ia), is characterized by decreased ability of the liver to convert glucose-6-phosphate to glucose leading to glycogen accumulation and ... Full text Link to item Cite

Laboratory analysis of amino acids, 2018 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG).

Journal Article Genet Med · December 2018 Amino acid abnormalities are observed in a broad spectrum of inherited metabolic diseases, such as disorders of amino acid metabolism and transport, organic acidemias, and ureagenesis defects. Comprehensive analysis of physiologic amino acids in blood, uri ... Full text Link to item Cite

Acetyl-l-carnitine deficiency in patients with major depressive disorder.

Journal Article Proc Natl Acad Sci U S A · August 21, 2018 The lack of biomarkers to identify target populations greatly limits the promise of precision medicine for major depressive disorder (MDD), a primary cause of ill health and disability. The endogenously produced molecule acetyl-l-carnitine (LAC) is critica ... Full text Link to item Cite

Laboratory diagnosis of creatine deficiency syndromes: a technical standard and guideline of the American College of Medical Genetics and Genomics.

Journal Article Genet Med · February 2017 Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these standards and guidelines is voluntary and does ... Full text Link to item Cite

Potential mechanisms for low uric acid in Parkinson disease.

Journal Article J Neural Transm (Vienna) · April 2016 Several epidemiologic studies have described an association between low serum uric acid (UA) and Parkinson disease (PD). Uric acid is a known antioxidant, and one proposed mechanism of neurodegeneration in PD is oxidative damage of dopamine neurons. Howeve ... Full text Link to item Cite

Natural Progression of Canine Glycogen Storage Disease Type IIIa.

Journal Article Comp Med · February 2016 Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of glycogen debranching enzyme activity. Hepatomegaly, muscle degeneration, and hypoglycemia occur in human patients at an early age. Long-term complications include liver cirrhosis, h ... Open Access Link to item Cite

Combined aerobic exercise and enzyme replacement therapy rejuvenates the mitochondrial-lysosomal axis and alleviates autophagic blockage in Pompe disease.

Journal Article Free Radic Biol Med · October 2015 A unifying feature in the pathogenesis of aging, neurodegenerative disease, and lysosomal storage disorders is the progressive deposition of macromolecular debris impervious to enzyme catalysis by cellular waste disposal mechanisms (e.g., lipofuscin). Aero ... Full text Link to item Cite

Complex III deficiency due to an in-frame MT-CYB deletion presenting as ketotic hypoglycemia and lactic acidosis.

Journal Article Mol Genet Metab Rep · September 2015 Complex III deficiency due to a MT-CYB mutation has been reported in patients with myopathy. Here, we describe a 15-year-old boy who presented with metabolic acidosis, ketotic hypoglycemia and carnitine deficiency. Electron transport chain analysis and mit ... Full text Link to item Cite

A straightforward, quantitative ultra-performance liquid chromatography-tandem mass spectrometric method for heparan sulfate, dermatan sulfate and chondroitin sulfate in urine: an improved clinical screening test for the mucopolysaccharidoses.

Journal Article Mol Genet Metab · February 2015 Mucopolysaccharidoses (MPS) are complex storage disorders that result in the accumulation of glycosaminoglycans (GAGs) in urine, blood, brain and other tissues. Symptomatic patients are typically screened for MPS by analysis of GAG in urine. Current screen ... Full text Link to item Cite

Baseline Urinary Glucose Tetrasaccharide Concentrations in Patients with Infantile- and Late-Onset Pompe Disease Identified by Newborn Screening.

Chapter · 2015 PURPOSE: The urinary glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc (Glc4), is a biomarker of glycogen accumulation and tissue damage and is elevated in patients with Pompe disease. We report baseline urinary Glc4 concentrations for patients with classi ... Full text Link to item Cite

Expanding the Clinical Spectrum of Mitochondrial Citrate Carrier (SLC25A1) Deficiency: Facial Dysmorphism in Siblings with Epileptic Encephalopathy and Combined D,L-2-Hydroxyglutaric Aciduria.

Chapter · 2015 Recessive mutations in SLC25A1 encoding mitochondrial citrate carrier cause a rare inherited metabolic disorder, combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA), characterized by epileptic encephalopathy, respiratory insufficiency, developmental arrest ... Full text Link to item Cite

Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia.

Journal Article Hum Mol Genet · September 15, 2014 Dienoyl-CoA reductase (DECR) deficiency with hyperlysinemia is a rare disorder affecting the metabolism of polyunsaturated fatty acids and lysine. The molecular basis of this condition is currently unknown. We describe a new case with failure to thrive, de ... Full text Link to item Cite

Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.

Journal Article FASEB journal : official publication of the Federation of American Societies for Experimental Biology · May 2014 Effective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previo ... Full text Open Access Cite

Adjunctive β2-agonist treatment reduces glycogen independently of receptor-mediated acid α-glucosidase uptake in the limb muscles of mice with Pompe disease.

Journal Article FASEB J · May 2014 Enzyme or gene replacement therapy with acid α-glucosidase (GAA) has achieved only partial efficacy in Pompe disease. We evaluated the effect of adjunctive clenbuterol treatment on cation-independent mannose-6-phosphate receptor (CI-MPR)-mediated uptake an ... Full text Open Access Link to item Cite

Assessment of toxicity and biodistribution of recombinant AAV8 vector-mediated immunomodulatory gene therapy in mice with Pompe disease.

Journal Article Mol Ther Methods Clin Dev · 2014 A preclinical safety study was conducted to evaluate the short- and long-term toxicity of a recombinant adeno-associated virus serotype 8 (AAV2/8) vector that has been developed as an immune-modulatory adjunctive therapy to recombinant human acid α-glucosi ... Full text Open Access Link to item Cite

Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia.

Journal Article Proc Natl Acad Sci U S A · August 13, 2013 Isolated methylmalonic acidemia (MMA), caused by deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT), is often complicated by end stage renal disease that is resistant to conventional therapies, including liver transplantation. To establi ... Full text Link to item Cite

Elevation of guanidinoacetate in newborn dried blood spots and impact of early treatment in GAMT deficiency.

Journal Article Mol Genet Metab · June 2013 Guanidinoacetate methyltransferase (GAMT) deficiency is a good candidate disorder for newborn screening because early treatment appears to improve outcomes. We report elevation of guanidinoacetate in archived newborn dried blood spots for 3 cases (2 famili ... Full text Link to item Cite

Quantification of glycosaminoglycans in urine by isotope-dilution liquid chromatography-electrospray ionization tandem mass spectrometry.

Journal Article Curr Protoc Hum Genet · 2013 Mucopolysaccharidoses (MPSs) are complex lysosomal storage disorders that result in the accumulation of glycosaminoglycans (GAGs) in urine, blood, and tissues. Lysosomal enzymes responsible for GAG degradation are defective in MPSs. GAGs including chondroi ... Full text Link to item Cite

Systemic oxidative stress, as measured by urinary allantoin and F(2)-isoprostanes, is not increased in Down syndrome.

Journal Article Ann Epidemiol · December 2012 PURPOSE: Oxidative stress has been implicated in Down syndrome (DS) pathology. This study compares DS individuals and controls on their urinary levels of allantoin and 2,3-dinor-iPF2α-III; these biomarkers have been previously validated in a clinical model ... Full text Link to item Cite

Quantitative computed tomography for enzyme replacement therapy in Pompe disease.

Journal Article Brain Dev · November 2012 OBJECTIVE: Pompe disease is an autosomal recessive disorder caused by deficiency of the lysosomal enzyme, acid alpha-glucosidase (GAA). To the best of our knowledge, no studies have reported the results of systematic and sequential CT analyses before and d ... Full text Link to item Cite

The emerging phenotype of long-term survivors with infantile Pompe disease.

Journal Article Genet Med · September 2012 PURPOSE: Enzyme replacement therapy with alglucosidase alfa for infantile Pompe disease has improved survival creating new management challenges. We describe an emerging phenotype in a retrospective review of long-term survivors. METHODS: Inclusion criteri ... Full text Open Access Link to item Cite

QUANTIFICATION OF GLYCOSAMINOGLYCANS IN HUMAN URINE AND MOUSE TISSUE BY UPLC-MS/MS

Journal Article JOURNAL OF INHERITED METABOLIC DISEASE · September 1, 2012 Link to item Cite

An improved method for glycosaminoglycan analysis by LC-MS/MS of urine samples collected on filter paper.

Journal Article Clin Chim Acta · April 11, 2012 BACKGROUND: Mucopolysaccharidoses are complex lysosomal storage disorders caused by any of eleven different enzyme deficiencies resulting in the accumulation of substrates, mainly glycosaminoglycans (GAGs), in various tissues and biological fluids. METHOD: ... Full text Link to item Cite

Assessing disease severity in Pompe disease: the roles of a urinary glucose tetrasaccharide biomarker and imaging techniques.

Journal Article Am J Med Genet C Semin Med Genet · February 15, 2012 Defining disease severity in patients with Pompe disease is important for prognosis and monitoring the response to therapies. Current approaches include qualitative and quantitative assessments of the disease burden, and clinical measures of the impact of ... Full text Link to item Cite

Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease.

Journal Article Genet Med · January 2012 PURPOSE: Infantile Pompe disease resulting from a deficiency of lysosomal acid α-glucosidase (GAA) requires enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA). Cross-reactive immunologic material negative (CRIM-negative) Pompe patients dev ... Full text Link to item Cite

Urinary F2-isoprostanes as a biomarker of reduced risk of type 2 diabetes.

Journal Article Diabetes Care · January 2012 OBJECTIVE: We have previously reported evidence of an inverse association between a urinary F(2)-isoprostane and type 2 diabetes risk in a pilot case-control study nested within the Insulin Resistance Atherosclerosis Study (IRAS). Here, we report the resul ... Full text Link to item Cite

Atypical immunologic response in a patient with CRIM-negative Pompe disease.

Journal Article Mol Genet Metab · December 2011 We report the clinical course of a patient with severe infantile onset Pompe disease [cross-reactive immunologic material (CRIM) negative, R854X/R854X] who was diagnosed prenatally and received standard dosing of alglucosidase alfa (Myozyme®) enzyme replac ... Full text Link to item Cite

Analysis of glycosaminoglycans in cerebrospinal fluid from patients with mucopolysaccharidoses by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry.

Journal Article Clin Chem · July 2011 Featured Publication BACKGROUND: New therapies for the treatment of mucopolysaccharidoses that target the brain, including intrathecal enzyme replacement, are being explored. Quantitative analysis of the glycosaminoglycans (GAGs) that accumulate in these disorders is required ... Full text Link to item Cite

Follow-up of a child with pyruvate dehydrogenase deficiency on a less restrictive ketogenic diet.

Journal Article Mol Genet Metab · February 2011 A male child with X-linked pyruvate dehydrogenase deficiency presented with severe neonatal lactic acidosis. Poor compliance following initiation of the ketogenic diet justified modification to a less restrictive form which improved compliance. One year af ... Full text Link to item Cite

Efficient analysis of urinary glycosaminoglycans by LC-MS/MS in mucopolysaccharidoses type I, II and VI.

Journal Article Mol Genet Metab · January 2011 Mucopolysaccharidoses (MPSs) are complex storage disorders caused by specific lysosomal enzyme deficiencies, resulting in the accumulation of glycosaminoglycans (GAGs) in urine, plasma, as well as in various tissues. We devised and validated a straightforw ... Full text Link to item Cite

Individual responses to chemotherapy-induced oxidative stress.

Journal Article Breast Cancer Res Treat · January 2011 Differences in redox homeostatic control between cancer patients may underlie predisposition to drug resistance and toxicities. To evaluate interindividual differences in redox response among newly diagnosed breast cancer patients undergoing standard chemo ... Full text Link to item Cite

GLYCOSAMINOGLYCAN QUANTIFICATION BY LC/MS-MS FOR MUCOPOLYSACCHARIDOSES

Conference JOURNAL OF INHERITED METABOLIC DISEASE · January 1, 2011 Link to item Cite

How well does urinary lyso-Gb3 function as a biomarker in Fabry disease?

Journal Article Clin Chim Acta · December 14, 2010 BACKGROUND: Fabry disease is characterized by accumulation of glycosphingolipids, such as globotriaosylceramide (Gb(3)), in many tissues and body fluids. A novel plasma biomarker, globotriaosylsphingosine (lyso-Gb(3)), is increased in patients with the dis ... Full text Link to item Cite

Allantoin in human urine quantified by ultra-performance liquid chromatography-tandem mass spectrometry.

Journal Article Anal Biochem · July 15, 2010 Featured Publication Uric acid is a potent antioxidant and scavenger of singlet oxygen and other radicals in humans. Allantoin, the predominant product of free radical-induced oxidation of uric acid, is efficiently excreted in the urine and has potential as a biomarker of oxid ... Full text Link to item Cite

Urinary biomarkers of oxidative status in a clinical model of oxidative assault.

Journal Article Cancer Epidemiol Biomarkers Prev · June 2010 BACKGROUND: We used doxorubicin-based chemotherapy as a clinical model of oxidative assault in humans. METHODS: The study recruited newly diagnosed breast cancer patients (n = 23). Urine samples were collected immediately before (T0) and at 1 hour (T1) and ... Full text Link to item Cite

Quantification of the oxidative damage biomarker 2,3-dinor-8-isoprostaglandin-F(2alpha) in human urine using liquid chromatography-tandem mass spectrometry.

Journal Article Anal Biochem · April 15, 2010 Featured Publication F(2)-isoprostanes are useful biomarkers of oxidative status in humans. We developed an ultraperformance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify 2,3-dinor-8-iso prostaglandin F(2alpha), a urinary metabolite of 8-iso-p ... Full text Link to item Cite

Immunomodulatory gene therapy prevents antibody formation and lethal hypersensitivity reactions in murine pompe disease.

Journal Article Mol Ther · February 2010 Featured Publication Infantile Pompe disease progresses to a lethal cardiomyopathy in absence of effective treatment. Enzyme-replacement therapy (ERT) with recombinant human acid alpha-glucosidase (rhGAA) has been effective in most patients with Pompe disease, but efficacy was ... Full text Link to item Cite

7. A urinary glycosaminoglycan analysis by tandem mass spectrometry

Conference Molecular Genetics and Metabolism · February 2010 Full text Cite

8. How useful is urinary lyso-Gb3 as a biomarker for Fabry disease?

Conference Molecular Genetics and Metabolism · February 2010 Full text Cite

Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants.

Journal Article Mol Genet Metab · January 2010 Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy. Patients synthesize a non-functional form of GAA or are unable to form native enzyme. Enzyme replacement therapy with recombinant human GAA ... Full text Link to item Cite

Impaired clearance of accumulated lysosomal glycogen in advanced Pompe disease despite high-level vector-mediated transgene expression.

Journal Article J Gene Med · October 2009 Featured Publication BACKGROUND: Infantile-onset glycogen storage disease type II (GSD-II; Pompe disease; MIM 232300) causes death early in childhood from cardiorespiratory failure in the absence of effective treatment, whereas late-onset Pompe disease causes a progressive ske ... Full text Link to item Cite

Gb(3)/creatinine biomarkers for Fabry disease: issues to consider.

Journal Article Mol Genet Metab · July 2009 Featured Publication Full text Link to item Cite

Long-term monitoring of patients with infantile-onset Pompe disease on enzyme replacement therapy using a urinary glucose tetrasaccharide biomarker.

Journal Article Genet Med · July 2009 Featured Publication PURPOSE: To investigate the correlation of the urinary glucose tetrasaccharide, Glcalpha1-6Glcalpha1-4Glcalpha1-4Glc, (Glc4) with skeletal muscle glycogen content and the long-term clinical response to enzyme replacement therapy with recombinant human acid ... Full text Link to item Cite

Screening for Pompe disease using a rapid dried blood spot method: experience of a clinical diagnostic laboratory.

Journal Article Muscle Nerve · July 2009 Featured Publication Pompe disease (acid maltase deficiency; glycogen storage disease type II) is caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Our clinical laboratory began to offer a fluorometric dried blood spot (DBS)-based GAA activity assay fo ... Full text Link to item Cite

Proposed high-risk screening protocol for Fabry disease in patients with renal and vascular disease.

Journal Article J Inherit Metab Dis · April 2009 Featured Publication Fabry disease is a complex, multisystemic and clinically heterogeneous disease with prominent urinary excretion of globotriaosylceramide (Gb(3)), the principal substrate of the deficient enzyme, alpha-galactosidase A. Some measure of specific treatment is ... Full text Link to item Cite

Development of tandem mass spectrometry assays for biomarkers of oxidative stress in urine

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 22, 2009 Link to item Cite

A convenient LC-MS method for assessment of glucose kinetics in vivo with D-[13C6]glucose as a tracer.

Journal Article Clin Chem · March 2009 Featured Publication BACKGROUND: The isotope-labeled intravenous glucose tolerance test (IVGTT) combined with computer modeling is widely used to derive parameters related to glucose metabolism in vivo. Most of these methods involve use of either (2)H(2)-labeled or (13)C(1)-la ... Full text Link to item Cite

7. An efficient high-risk screening protocol for Fabry disease

Journal Article Molecular Genetics and Metabolism · February 2009 Full text Cite

Biomarkers in fabry disease

Conference Clinical Therapeutics · January 2009 Full text Cite

Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

Journal Article Mol Genet Metab · December 2008 Featured Publication Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those wi ... Full text Link to item Cite

Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy.

Journal Article Mol Ther · August 2008 Featured Publication Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the deficiency of acid alpha-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. An adeno-associated virus 2/8 (AAV2/8) vector containi ... Full text Link to item Cite

Enhanced response to enzyme replacement therapy in Pompe disease after the induction of immune tolerance.

Journal Article Am J Hum Genet · November 2007 Featured Publication Pompe disease, which results from mutations in the gene encoding the glycogen-degrading lysosomal enzyme acid alpha -glucosidase (GAA) (also called "acid maltase"), causes death in early childhood related to glycogen accumulation in striated muscle and an ... Full text Link to item Cite

Quantification of creatine and guanidinoacetate using GC-MS and LC-MS/MS for the detection of cerebral creatine deficiency syndromes.

Journal Article Current protocols in human genetics · July 2007 Inherited defects in creatine biosynthesis and cellular uptake are neurometabolic disorders characterized by seizures, developmental delay, mental retardation, autistic-like behavior, and creatine deficiency in the brain. Metabolic screening of these disor ... Full text Cite

Disorders of amino acid metabolism

Chapter · January 1, 2007 Of the many genetic disorders that express themselves as specific defects of amino acid metabolism, some, including two of Garrod’s four original “inborn errors of metabolism” (albinism, alkaptonuria), produce significant abnormalities in the ocular tissue ... Cite

Enhanced efficacy of an AAV vector encoding chimeric, highly secreted acid alpha-glucosidase in glycogen storage disease type II.

Journal Article Mol Ther · December 2006 Featured Publication Glycogen storage disease type II (GSD-II; Pompe disease; MIM 232300) is an inherited muscular dystrophy caused by deficiency in the activity of the lysosomal enzyme acid alpha-glucosidase (GAA). We hypothesized that chimeric GAA containing an alternative s ... Full text Link to item Cite

Variations in IBD (ACAD8) in children with elevated C4-carnitine detected by tandem mass spectrometry newborn screening.

Journal Article Pediatr Res · September 2006 Featured Publication The isobutyryl-CoA dehydrogenase (IBD) enzyme is involved in the degradation of valine. IBD deficiency was first reported in 1998 and subsequent genetic investigations identified acyl-CoA dehydrogenase (ACAD) 8, now IBD, as the gene responsible for IBD def ... Full text Link to item Cite

Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease.

Journal Article Genet Med · May 2006 Featured Publication PURPOSE: The study's purpose was to compare acarbose and maltose as inhibitors of maltase-glucoamylase activity for determining acid alpha-glucosidase activity in dried blood spot specimens for early identification of patients with infantile Pompe disease, ... Full text Link to item Cite

Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II.

Journal Article Mol Ther · November 2005 Featured Publication Glycogen storage disease type II (GSD-II; Pompe disease) is caused by a deficiency of acid alpha-glucosidase (GAA; acid maltase) and manifests as muscle weakness, hypertrophic cardiomyopathy, and respiratory failure. Adeno-associated virus vectors containi ... Full text Link to item Cite

Glucose tetrasaccharide as a biomarker for monitoring the therapeutic response to enzyme replacement therapy for Pompe disease.

Journal Article Mol Genet Metab · August 2005 Featured Publication A tetraglucose oligomer, Glcalpha1-6Glcalpha1-4Glcalpha1-4Glc, designated Glc4, has been shown to be a putative biomarker for the diagnosis of Pompe disease. The purpose of this study was to assess whether Glc4 could be used to monitor the therapeutic resp ... Full text Link to item Cite

Efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type II.

Journal Article Mol Ther · January 2005 Featured Publication Glycogen storage disease type II (GSD-II; Pompe disease) causes death in infancy from cardiorespiratory failure. The underlying deficiency of acid alpha-glucosidase (GAA; acid maltase) can be corrected by liver-targeted gene therapy in GSD-II, if secretion ... Full text Link to item Cite

A comparison of in vitro acylcarnitine profiling methods for the diagnosis of classical and variant short chain acyl-CoA dehydrogenase deficiency.

Journal Article Clin Chim Acta · November 2003 Featured Publication BACKGROUND: Homozygosity and compound heterozygosity for the short chain acyl-CoA dehydrogenase (SCAD) gene sequence variants 625G-->A and 511C-->T are associated with ethylmalonic aciduria (EMA), a biochemical indicator of SCAD deficiency. The clinical an ... Full text Link to item Cite

Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening.

Journal Article Pediatr Res · August 2003 Featured Publication Tandem mass spectrometry was adopted for newborn screening by North Carolina in April 1999. Since then, three infants with short-chain acyl-CoA dehydrogenase (SCAD) and one with isobutyryl-CoA dehydrogenase deficiency were detected on the basis of elevated ... Full text Link to item Cite

Analysis of a glucose tetrasaccharide elevated in Pompe disease by stable isotope dilution-electrospray ionization tandem mass spectrometry.

Journal Article Anal Biochem · May 15, 2003 Featured Publication Patients with glycogen storage disease type II (GSD II) typically excrete increased amounts of a glycogen-derived glucose tetrasaccharide, Glcalpha1-6Glcalpha1-4Glcalpha1-4Glc (Glc(4)), in the urine. With the advent of a new enzyme replacement therapy for ... Full text Link to item Cite

Isomeric oligosaccharide analysis using hydrophilic interaction LC-ESI-MS/MS

Journal Article Proceedings 50th ASMS Conference on Mass Spectrometry and Allied Topics · December 1, 2002 A hydrophilic interaction liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS/MS) method was established for the separation and analysis of hexose tetrasaccharide linkage isomers in urine, plasma and blood spots. Using the LC-ESI-MS/ ... Cite

Effects of phytanic acid on the vitamin E status, lipid composition and physical properties of retinal cell membranes: implications for adult Refsum disease.

Journal Article Clin Sci (Lond) · December 2001 Featured Publication Adult Refsum disease is an inherited disorder in which phytanic acid accumulates in tissues and serum. Two hypotheses have been proposed to explain the pathogenesis of this condition. The molecular distortion hypothesis suggests that phytanic acid may alte ... Link to item Cite

Liquid chromatographic assay for a glucose tetrasaccharide, a putative biomarker for the diagnosis of Pompe disease.

Journal Article Anal Biochem · December 1, 2000 Featured Publication A HPLC method associated with butyl-p-aminobenzoate derivatization has been developed for the analysis of a tetraglucose oligomer, Glcalpha1-6Glcalpha1-4Glcalpha1-4Glc, designated Glc(4), in biological fluids. This tetraglucose, normally excreted in the ur ... Full text Link to item Cite