Barbara K Burton

Northwestern University | NU

A systematic literature review was conducted to determine the global status of newborn screening (NBS) for mucopolysaccharidosis (MPS) II (Hunter syndrome; OMIM 309900). Electronic databases were searched in July 2023 for articles referencing NBS for lysosomal storage diseases: 53 featured MPS II. Until recently, only Taiwan and two US states (Illi...

Mucopolysaccharidosis II (MPS II; Hunter syndrome; OMIM 309900) is a rare, X‐linked, heterogeneous lysosomal storage disease. Approximately two‐thirds of patients develop cognitive impairment, which is difficult to assess in clinical trials, partly owing to the variable nature of cognitive impairment. Analyzing data from siblings can help to minimi...

Background Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII. Methods This disea...

Phenylketonuria (PKU) is a genetic disorder caused by deficiency of the enzyme phenylalanine hydroxylase (PAH), which results in phenylalanine (Phe) accumulation in the blood and brain, and requires lifelong treatment to keep blood Phe in a safe range. Pegvaliase is an enzyme-substitution therapy approved for individuals with PKU and uncontrolled b...

Background Mucopolysaccharidosis (MPS) II is a rare, X-linked lysosomal storage disease. Approximately two-thirds of patients have central nervous system involvement with some demonstrating progressive cognitive impairment (neuronopathic disease). The natural history of cognitive and adaptive function in patients with MPS II is not well-defined. Th...

A late-onset Pompe disease patient developed high sustained antibody titers (HSAT) of ≥51,200 after 11+ years on alglucosidase alfa and previous tolerance. There was a corresponding worsening of motor function and rise in urinary glucose tetrasaccharide (Glc4). Following immunomodulation therapy, HSAT were eliminated with improved clinical outcomes...

Long-chain fatty acid oxidation disorders (LC-FAODs) result in life-threatening energy metabolism deficiencies/energy source depletion. Triheptanoin is an odd-carbon, medium chain triglyceride (that is an anaplerotic substrate of calories and fatty acids) for treating pediatric and adult patients with LC-FAODs. Study CL202 (NCT02214160), an open-la...

Clinical trial development in rare diseases poses significant study design and methodology challenges, such as disease heterogeneity and appropriate patient selection, identification and selection of key endpoints, decisions on study duration, choice of control groups, selection of appropriate statistical analyses, and patient recruitment. Therapeu...

We describe our experience with population-based newborn screening for mucopolysaccharidosis type II (MPS II) in 586,323 infants by measurement of iduronate-2-sulfatase activity in dried blood spots between December 12, 2017 and April 30, 2022. A total of 76 infants were referred for diagnostic testing, 0.01% of the screened population. Of these, e...

Background Phenylketonuria (PKU) is an inborn metabolic error characterized by a deficiency of the enzyme required for the metabolism of phenylalanine, an essential amino acid found in most protein-containing foods. Pegvaliase (Palynziq®) is an enzyme substitution therapy approved for adults with PKU who have inadequate blood phenylalanine control...

Objective: KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants. Methods: We screened 893 individuals with developmental and epileptic encephalopathies (DEEs) for KCNH5 variants using targeted or exome sequencing. Additi...

Zinc finger nuclease (ZFN)-based in vivo genome editing is a novel treatment that can potentially provide lifelong protein replacement with single intravenous administration. Three first-in-human open-label ascending single-dose phase 1/2 studies were performed in parallel (starting November 2017) primarily to assess safety and tolerability of ZFN...

Two-thirds of patients with mucopolysaccharidosis II (MPS II; Hunter syndrome) have cognitive impairment. This phase 2/3, randomized, controlled, open-label, multicenter study (NCT02055118) investigated the effects of intrathecally administered idursulfase-IT on cognitive function in patients with MPS II. Children older than 3 years with MPS II and...

Enzyme replacement therapy with weekly infused intravenous (IV) idursulfase is effective in treating somatic symptoms of mucopolysaccharidosis II (MPS II; Hunter syndrome). A formulation of idursulfase for intrathecal administration (idursulfase-IT) is under investigation for the treatment of neuronopathic MPS II. Here, we report 36-month data from...

Purpose Nonmuscle myosin II complexes are master regulators of actin dynamics that play essential roles during embryogenesis with vertebrates possessing 3 nonmuscle myosin II heavy chain genes, MYH9, MYH10, and MYH14. As opposed to MYH9 and MYH14, no recognizable disorder has been associated with MYH10. We sought to define the clinical characterist...

Background The Morquio A Registry Study (MARS) is an ongoing, multinational, observational study of patients with MPS IVA. Key objectives of MARS are to characterize the heterogeneity and natural history of disease and to evaluate long-term effectiveness and safety of elosulfase alfa enzyme replacement therapy (ERT). Enrollment began in September 2...

The mucopolysaccharidoses (MPSs) are a group of lysosomal diseases, each characterized by a specific enzyme deficiency related to a specific gene defect that affects one of the steps of the stepwise degradation pathway of glycosaminoglycans, leading to progressive storage of these compounds in tissues and organs. These diseases are genetically very...

Background Early treated patients with phenylketonuria (PKU) often become lost to follow-up from adolescence onwards due to the historical focus of PKU care on the pediatric population and lack of programs facilitating the transition to adulthood. As a result, evidence on the management of adolescents and young adults with PKU is limited. Methods...

Objective KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants. Methods We screened 893 individuals with developmental and epileptic encephalopathies (DEEs) for KCNH5 variants using targeted or exome sequencing. Additional...

Objectives: Sebelipase alfa is approved for treatment of lysosomal acid lipase deficiency (LAL-D). This single-arm, open-label study (NCT02112994) evaluated sebelipase alfa efficacy and safety in patients with LAL-D. Methods: Patients >8 months of age diagnosed with LAL-D received sebelipase alfa 1.0 mg/kg by intravenous infusion every other wee...

All newborn screening (NBS) for mucopolysaccharidosis-I and -II (MPS-I and MPS-II) is carried out via the measurement of α-iduronidase (IDUA) and iduronate-2-sulfatase (IDS) enzymatic activity, respectively, in dried blood spots (DBS). The majority of low enzyme results are due to pseudodeficiencies, and data from recent MPS-II population screening...

X-linked adrenoleukodystrophy (X-ALD) is a genetic neurodegenerative disorder with an approximate incidence of 1 in 14,700 births. Both males and females are affected. Approximately one-third of affected males develop childhood cerebral adrenoleukodystrophy, which progresses rapidly to severe disability and death. In these cases, early surveillance...

Abstract Background Mucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare, life-limiting lysosomal storage disease caused by deficient iduronate-2-sulfatase activity. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase can stabilize or improve many somatic manifestations, but there remains a need for further analysis of long-t...

Background & Aims Children and adults with lysosomal acid lipase deficiency (LAL-D) experience cirrhosis and dyslipidemia from lysosomal accumulation of cholesteryl esters and triglycerides. Sebelipase alfa enzyme replacement therapy is indicated for individuals with LAL-D. We report final results of the phase 3 randomized ARISE study of sebelipase...

Phenylketonuria (PKU), a deficiency in the activity of the enzyme phenylalanine hydroxylase, leads to toxic levels of phenylalanine (Phe) in the blood and brain. Pegvaliase (recombinant Anabaena variabilis phenylalanine ammonia lyase conjugated with polyethylene glycol) is approved to manage PKU in patients aged greater than or equal to 18 years in...

Objective To provide updated evidence and consensus-based recommendations for the classification of individuals who screen positive for Krabbe Disease (KD) and recommendations for long-term follow-up for those who are at risk for late onset Krabbe Disease (LOKD). Methods KD experts (KD NBS Council) met between July 2017 and June 2020 to develop co...

Sapropterin dihydrochloride has been approved for the treatment of hyperphenylalaninemia in infants and young children with phenylketonuria (PKU). Sapropterin can reduce phenylalanine (Phe) levels in tetrahydrobiopterin (BH4)-responsive patients, potentially preventing the intellectual impairment caused by elevated Phe levels. The long-term effect...

Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare, progressive multisystemic lysosomal storage disorder with significant morbidity and premature mortality. Infants with MPS II develop signs and symptoms of the disorder in the early years of life, yet diagnostic delays are very common. Enzyme replacement therapy is an effective treat...

Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]–1:125,000 [Japan]). Comparing genotypes and metab...

Background Phenylketonuria (PKU) is characterized by a deficiency in phenylalanine hydroxylase (PAH) that may lead to elevated blood phenylalanine (Phe) and significant neurocognitive and neuropsychological comorbidities. Pegvaliase (PALYNZIQ®, BioMarin Pharmaceutical Inc.) is a PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase...

Objective: Previous research has documented executive function (EF) impairments in individuals with early treated phenylketonuria (ETPKU). It remains unclear, however, whether some aspects of EF may be more affected than others. A number of factors, including small sample sizes and variability in EF tasks, have likely contributed to past mixed fin...

Morquio syndrome type A, also known as MPS IVA, is a rare autosomal recessive disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase, a lysosomal hydrolase critical in the degradation of keratan sulfate and chondroitin sulfate. The chondroitin sulfate that accumulates in MPS IVA patients has a disease-specific non-reducing end terminati...

Objectives: To assess the outcome of population-based newborn screening for mucopolysaccharidosis type II (MPS II) during the first year of screening in Illinois. Study design: Tandem mass spectrometry was used to measure iduronate-2-sulfatase (I2S) activity in dried blood spot specimens obtained from 162 000 infant samples sent to the Newborn S...

Treatment for mucopolysaccharidosis type II (MPS II Hunter syndrome) is available in the form of intravenous enzyme replacement therapy (ERT) with idursulfase (Shire, Lexington, MA, USA). This analysis used statistical modelling to evaluate the long-term treatment effects of idursulfase on selected clinical parameters based on data from HOS, a glob...

Mucopolysaccharidosis type II (MPS II Hunter syndrome) is a rare, life-limiting, X-linked lysosomal storage disease. The Hunter Outcome Survey (HOS) is a Shire-sponsored, global, observational registry initiated in 2005 that collects real-world data on the natural history of MPS II and long-term treatment with enzyme replacement therapy (ERT) with...

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare, progressive, X-linked genetic disorder that is caused by mutations in the human IDS gene and is characterized by deficient activity of the lysosomal enzyme iduronate-2-sulfatase (IDS). Without functional IDS activity, the glycosaminoglycans (GAG), dermatan sulfate and heparan sulf...

Two-thirds of patients with mucopolysaccharidosis type II (MPS II Hunter syndrome), a rare lysosomal disease characterized by iduronate-2-sulfatase deficiency, have cognitive impairment. This observational, prospective, longitudinal study (NCT01822184) assessed cognitive status and adaptive behavior in patients aged 2−<18 years with MPS II patients...

Background: Krabbe disease is a rare neurodegenerative genetic disorder caused by deficiency of galactocerebrosidase. Patients with the infantile form of Krabbe disease can be treated at a presymptomatic stage with human stem cell transplantation which improves survival and clinical outcomes. However, without a family history, most cases of infant...

Background Deficiency of phenylalanine hydroxylase causes phenylketonuria (PKU) with elevated phenylalanine (Phe) levels and associated neuropsychiatric and neurocognitive symptoms. Pegvaliase (PEGylated phenylalanine ammonia lyase) is an investigational agent to lower plasma Phe in adults with PKU. This study aimed to characterize the long-term ef...

Background: Phenylalanine hydroxylase (PAH) deficiency, otherwise known as phenylketonuria (PKU), is an inborn error of metabolism that requires treatment to be initiated in the newborn period and continued throughout life. Due to the challenges of treatment adherence and the resulting cumulative effects of high and labile blood phenylalanine, PKU...