Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy

Burlina, Alberto; Polo, Giulia; Salviati, Leonardo; Duro, Giovanni; Zizzo, Carmela; Dardis, Andrea; Bembi, Bruno; Cazzorla, Chiara; Rubert, Laura; Zordan, Roberta; Desnick, Robert J.; Burlina, Alessandro P.

doi:10.1007/s10545-017-0098-3

Cited by 144 publications

(117 citation statements)

References 44 publications

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“…However, the choice of low (and therefore sensitive) enzyme thresholds is partially responsible for the lack of an acceptable balance between false positive and negative screens in NBS, as reported for the two disorders to which BVNL diagnostic tools have now been applied: KD 13,33 and MPSI. [14][15][16][17][18][19] There is also ethically motivated urgency to reduce high false positive rates. 32 Using more aggressive thresholds to reduce false positive screens in a univariate test may, however, increase false negative screens.…”

Section: Discussionmentioning

confidence: 99%

“…This would represent a remarkable improvement in NBS for MPSI. [14][15][16][17][18][19] No new case was identified among the 5000 prospective screens from the Gifu prefecture. New York State recently reported the results of 65 000 LSDs newborn screens.…”

Section: Discussionmentioning

confidence: 99%

“…12,13 Pilot studies were, for example, performed with dried blood spots (DBS) in Taiwan 14 and in Italy. 15 The PPV values for MPSI were 26.7% and 7.7%, respectively. In the United States, pilot studies conducted, for example, in Kentucky, 16 Illinois, 17 Missouri 18 and New York, 19 respectively, yielded PPVs of 50%, 0.46%, 3.0%, and 0% for MPSI NBS.…”

Section: Introductionmentioning

confidence: 93%

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Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

et al. 2020

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Purpose Current newborn screening (NBS) for mucopolysaccharidosis type I (MPSI) has very high false positive rates and low positive predictive values (PPVs). To improve the accuracy of presymptomatic prediction for MPSI, we propose an NBS tool based on known biomarkers, alpha‐L‐iduronidase enzyme activity (IDUA) and level of the glycosaminoglycan (GAG) heparan sulfate (HS). Methods We developed the NBS tool using measures from dried blood spots (DBS) of 5000 normal newborns from Gifu Prefecture, Japan. The tool's predictive accuracy was tested on the newborn DBS from these infants and from seven patients who were known to have early‐onset MPSI (Hurler's syndrome). Bivariate analyses of the standardized natural logarithms of IDUA and HS levels were employed to develop the tool. Results Every case of early‐onset MPSI was predicted correctly by the tool. No normal newborn was incorrectly identified as having early‐onset MPSI, whereas 12 normal newborns were so incorrectly identified by the Gifu NBS protocol. The PPV was estimated to be 99.9%. Conclusions Bivariate analysis of IDUA with HS in newborn DBS can accurately predict early MPSI symptoms, control false positive rates, and enhance presymptomatic treatment. This bivariate analysis‐based approach, which was developed for Krabbe disease, can be extended to additional screened disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

et al. 2020

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“…Recent studies suggest that the disease might be less rare than estimated in previous surveys because the atypic variant of the disease is underdiagnosed and the actual incidence of the disease may be approximately 1:8.800 individuals [3].…”

Section: Introductionmentioning

confidence: 92%

Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients from a Southern Italy Area

Zizzo¹,

Testa²,

Colomba³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Fabry disease (FD) is a lysosomal storage disorder characterized by pervasive renal involvement. However, this disease is underdiagnosed in patient with chronic kidney disease (CKD), including those with end stage renal disease (ESRD), so their investigation represents an unexploited opportunity for early diagnosis of the disease and for its identification in relatives of affected patients. Methods: We investigated Fabry disease in a clinical and biological database including ESRD patients of unknown cause in a geographical area with 2 million residents. The study was based on state of art GLA gene sequencing and was extended to relatives of affected ESRD patients. Results: Among ESRD patients qualified for enrollment into this study, a previously undiagnosed young man harboring the mutation p.I91T was identified. The study of the proband's family led to the identification of 8 additional cases. In another ESRD male patient, we identified the functional polymorphism p.D313Y. Furthermore, in 55 ESRD patients (24.2%) we found intronic polymorphisms of uncertain functional relevance in the non-coding regions of the GLA gene. Conclusion: A comprehensive survey of ESRD patients in a geographical area of 2 million residents identified one undiagnosed case of Fabry disease and led to the identification of 8 additional cases among his relatives. Screening protocols starting from the dialysis population and upstream extended to families of affected individuals may be an effective strategy to maximize the early identification of subjects with Fabry disease.

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“…This consideration is supported by the fact that incidence of FD late-onset phenotype in Europe is 8 to 20-fold as frequent as incidence of classic phenotype, as shown in the newborn screening studies. 14,15 Only 12% of Fabry patients with amenable mutations are actually treated with migalastat. These patients had classic or late-onset phenotype.…”

Section: Discussionmentioning

confidence: 99%

Fabry disease genotype, phenotype, and migalastat amenability: Insights from a national cohort

Nowak

Huynh‐Do

Krayenbuehl

et al. 2019

J of Inher Metab Disea

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Fabry disease (FD) is a rare X‐linked lysosomal storage disorder caused by α‐galactosidase A (α‐Gal A) deficiency. The progressive accumulation of globotriaosylceramide results in life‐threatening complications, including renal, cardiac, and cerebrovascular diseases. The pharmacological chaperone migalastat was recently approved as an alternative to enzyme replacement therapy in patients with amenable mutations. In this article, we investigate the proportion of amenable mutations, related to phenotype, in a population of adult patients with FD in Switzerland. This study included 170 adult patients (n = 64 males) from 46 independent pedigrees with 39 different identified mutations over the last 59 years. Overall, 68% had the classic phenotype and 48% fulfilled the current amenability criteria. Migalastat was stopped in 2/11 (18%) patients: the only male classic patient, because of lack of efficacy based on lyso‐Gb3 levels, and one patient with a benign variant. In males, the achieved enzyme activities in peripheral leucocytes under migalastat treatment differed from the activities in HEK‐cells after incubation with migalastat (eg, 33% in PL vs 41% HEK‐cells for p.F113L; 43% in leucocytes vs 36% in HEK‐cells for p.N215S, 24‐30% in leucocytes vs 96% in HEK‐cells for S238N). In this national cohort, we found a relatively high proportion of patients with amenable GLA mutations, which, however, had heterogeneous extent of amenability: the higher the residual α‐Gal A activity, the higher the chaperone effect. Further studies are required to investigate the long‐term benefits of migalastat therapy depending on the achieved enzyme activities in different amenable mutations.

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Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy

Abstract: Simultaneously determining multiple enzyme activities by MS/MS, with a focus on specific biochemical markers, successfully detected newborns with LSDs. The high incidence of these disorders supports this screening program.

Cited by 144 publications

References 44 publications

Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha‐L‐iduronidase determinations on dried blood spots to predict symptoms

Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients from a Southern Italy Area

Fabry disease genotype, phenotype, and migalastat amenability: Insights from a national cohort

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