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Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant.

Publication ,  Journal Article
Rairikar, MV; Case, LE; Bailey, LA; Kazi, ZB; Desai, AK; Berrier, KL; Coats, J; Gandy, R; Quinones, R; Kishnani, PS
Published in: Mol Genet Metab
November 2017

OBJECTIVE: Newborn screening (NBS) has led to early diagnosis and early initiation of treatment for infantile onset Pompe Disease (IOPD). However, guidelines for management of late onset Pompe disease (LOPD) via NBS, especially with the IVS c.-32-13T>G are not clear. This IVS variant is noted in 68-90% cases with LOPD and has been presumed to result in "adult" disease in compound heterozygosity, with a few cases with earlier onset and a mild to no phenotype in homozygosity. Our study evaluates newborns with LOPD having IVS variant with a diligent multidisciplinary approach to determine if they have an early presentation. METHODS: Seven children with LOPD identified by NBS with IVS variant (3 compound heterozygous, and 4 homozygous) were evaluated with clinical, biochemical (CK, AST, ALT, and urinary Glc4), cardiac evaluation, physical therapy (PT), occupational, and speech/language therapy. RESULTS: All seven patients demonstrated motor involvement by age 6months; the three patients with c.-32-13 T>G variant in compound heterozygosity had symptoms as neonates. Patients with c.-32-13 T>G variant in compound heterozygosity had more involvement with persistent hyperCKemia, elevated AST and ALT, swallowing difficulties, limb-girdle weakness, delayed motor milestones, and were initiated on ERT. The patients with c.-32-13T>G variant in homozygosity had normal laboratory parameters, and presented with very subtle yet LOPD specific signs, identified only by meticulous assessments. CONCLUSION: This patient cohort represents the first carefully phenotyped cohort of infants with LOPD with the "late-onset" GAA variant c.-32-13T>G detected by NBS in the USA. It emphasizes not only the opportunity for early detection of skeletal and other muscle involvement in infants with c.-32-13T>G variant but also a high probability of overlooking or underestimating the significance of clinically present and detectable features. It can thus serve as a valuable contribution in the development of evaluation and treatment algorithms for infants with LOPD.

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Published In

Mol Genet Metab

DOI

EISSN

1096-7206

Publication Date

November 2017

Volume

122

Issue

3

Start / End Page

99 / 107

Location

United States

Related Subject Headings

  • Phenotype
  • Neonatal Screening
  • Mutation
  • Male
  • Infant, Newborn
  • Infant
  • Humans
  • Homozygote
  • Heterozygote
  • Glycogen Storage Disease Type II
 

Citation

APA
Chicago
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Rairikar, M. V., Case, L. E., Bailey, L. A., Kazi, Z. B., Desai, A. K., Berrier, K. L., … Kishnani, P. S. (2017). Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant. Mol Genet Metab, 122(3), 99–107. https://doi.org/10.1016/j.ymgme.2017.09.008
Rairikar, Mugdha V., Laura E. Case, Lauren A. Bailey, Zoheb B. Kazi, Ankit K. Desai, Kathryn L. Berrier, Julie Coats, Rachel Gandy, Rebecca Quinones, and Priya S. Kishnani. “Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant.Mol Genet Metab 122, no. 3 (November 2017): 99–107. https://doi.org/10.1016/j.ymgme.2017.09.008.
Rairikar MV, Case LE, Bailey LA, Kazi ZB, Desai AK, Berrier KL, et al. Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant. Mol Genet Metab. 2017 Nov;122(3):99–107.
Rairikar, Mugdha V., et al. “Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant.Mol Genet Metab, vol. 122, no. 3, Nov. 2017, pp. 99–107. Pubmed, doi:10.1016/j.ymgme.2017.09.008.
Rairikar MV, Case LE, Bailey LA, Kazi ZB, Desai AK, Berrier KL, Coats J, Gandy R, Quinones R, Kishnani PS. Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant. Mol Genet Metab. 2017 Nov;122(3):99–107.
Journal cover image

Published In

Mol Genet Metab

DOI

EISSN

1096-7206

Publication Date

November 2017

Volume

122

Issue

3

Start / End Page

99 / 107

Location

United States

Related Subject Headings

  • Phenotype
  • Neonatal Screening
  • Mutation
  • Male
  • Infant, Newborn
  • Infant
  • Humans
  • Homozygote
  • Heterozygote
  • Glycogen Storage Disease Type II