Newborn Screening for Lysosomal Storage Disorders: Clinical Evaluation of a Two-Tier Strategy

Meikle, Peter J.; Ranieri, Enzo; Simonsen, Henrik Toft; Rozaklis, Tina; Ramsay, Steve L.; Whitfield, Phillip D.; Fuller, Maria; Christensen, Ernst; Skovby, Flemming; Hopwood, John J.

doi:10.1542/peds.2004-0583

Cited by 100 publications

(66 citation statements)

References 28 publications

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“…Methods for high throughput screening of GAA activity, using the newborn screening dried blood filter specimen (DBS), have been developed and are being validated in large population screening programs 29–31,107. If successful, newborn screening for Pompe disease can become a reality.…”

Section: Genetic Counseling Prenatal Diagnosis and Screeningmentioning

confidence: 99%

Pompe disease diagnosis and management guideline

Kishnani

Steiner

Bali

et al. 2006

Genetics in Medicine

503

583

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Section: Genetic Counseling Prenatal Diagnosis and Screeningmentioning

confidence: 99%

Pompe disease diagnosis and management guideline

Kishnani

Steiner

Bali

et al. 2006

Genetics in Medicine

503

583

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“…Early diagnosis will thus be essential and can only be achieved by increasing awareness for MPS III and, probably best, by NBS. Earlier studies showed that NBS for MPS IIIA is feasible, for example, by measuring HS concentrations or lysosomal protein concentrations in dried blood spots 22, 31, 32. Early diagnosis, especially through NBS, will make reliable assessment of the phenotype crucial, either by genotyping or, if that is inconclusive, by other methods such as the method reported here.…”

Section: Discussionmentioning

confidence: 87%

Prediction of phenotypic severity in mucopolysaccharidosis type IIIA

Knottnerus

Nijmeijer

IJlst

et al. 2017

Annals of Neurology

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ObjectiveMucopolysaccharidosis IIIA or Sanfilippo disease type A is a progressive neurodegenerative disorder presenting in early childhood, caused by an inherited deficiency of the lysosomal hydrolase sulfamidase. New missense mutations, for which genotype–phenotype correlations are currently unknown, are frequently reported, hampering early prediction of phenotypic severity and efficacy assessment of new disease‐modifying treatments. We aimed to design a method to determine phenotypic severity early in the disease course.MethodsFifty‐three patients were included for whom skin fibroblasts and data on disease course and mutation analysis were available. Patients were phenotypically characterized on clinical data as rapidly progressing or slowly progressing. Sulfamidase activity was measured in fibroblasts cultured at 37 °C and at 30 °C.ResultsSulfamidase activity in fibroblasts from patients homozygous or compound heterozygous for a combination of known severe mutations remained below the limit of quantification under both culture conditions. In contrast, sulfamidase activity in fibroblasts from patients homozygous or compound heterozygous for a known mild mutation increased above the limit of quantification when cultured at 30 °C. With division on the basis of the patients' phenotype, fibroblasts from slowly progressing patients could be separated from rapidly progressing patients by increase in sulfamidase activity when cultured at 30 °C (p < 0.001, sensitivity = 96%, specificity = 93%).InterpretationPhenotypic severity strongly correlates with the potential to increase sulfamidase activity in fibroblasts cultured at 30 °C, allowing reliable distinction between patients with rapidly progressing or slowly progressing phenotypes. This method may provide an essential tool for assessment of treatment effects and for health care and life planning decisions. Ann Neurol 2017;82:686–696

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“…The diagnosis may be confi rmed by assay of enzyme levels in tissue samples and gene sequencing. Prenatal diagnosis is possible 7 .…”

Section: The Casementioning

confidence: 99%

“…Treatment remains largely supportive 7 . The behavioral disturbances of MPS-III respond poorly to medication.…”

Section: The Casementioning

confidence: 99%