Tags

Type your tag names separated by a space and hit enter

Rapidly Progressive White Matter Involvement in Early Childhood: The Expanding Phenotype of Infantile Onset Pompe?
JIMD Rep. 2018; 39:55-62.JR

Abstract

Glycogen accumulation in the central nervous system of patients with classical infantile onset Pompe disease (IOPD) has been a consistent finding on the few post-mortems performed. While delays in myelination and a possible reduction in processing speed have previously been noted, it has only been recently that the potential for clinically significant progressive white matter disease has been noted. The limited reports thus far published infer that in some IOPD patients, this manifests as intellectual decline in the second decade of life. We present a CRIM negative patient, immunomodulated with rituximab and methotrexate at birth, who despite an initial good clinical response to ERT, at the age of just under 4 years, presented with evolving spasticity in the lower limbs. The investigation of which revealed progressive central nervous system involvement. Given both the earlier onset of the symptoms and consanguineous familial pedigree, extensive biochemical and genetic investigation was undertaken to ensure no alternative pathology was elucidated. In light of these findings, we review the radiology and post-mortems of previous cases and discuss the potential mechanisms that may underlie this presentation.

Authors+Show Affiliations

Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester Foundation Trust, Manchester, M13 9WL, UK. alexander.broomfield@cmft.nhs.uk.Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester Foundation Trust, Manchester, M13 9WL, UK.Department of Physiotherapy, Royal Manchester Children's Hospital, Central Manchester Foundation Trust, Manchester, M13 9WL, UK.Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester Foundation Trust, Manchester, M13 9WL, UK.Department of Biochemistry, Great Ormond Street Hospital, Great Ormond Street, London, WC1N 3JH, UK.Department of Paediatric Neuroradiology, Royal Manchester Children's Hospital, Central Manchester Foundation Trust, Manchester, M13 9WL, UK.Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, St Mary's Hospital, Central Manchester Foundation Trust, Manchester, M13 9WL, UK.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28726123

Citation

Broomfield, A, et al. "Rapidly Progressive White Matter Involvement in Early Childhood: the Expanding Phenotype of Infantile Onset Pompe?" JIMD Reports, vol. 39, 2018, pp. 55-62.
Broomfield A, Fletcher J, Hensman P, et al. Rapidly Progressive White Matter Involvement in Early Childhood: The Expanding Phenotype of Infantile Onset Pompe? JIMD Rep. 2018;39:55-62.
Broomfield, A., Fletcher, J., Hensman, P., Wright, R., Prunty, H., Pavaine, J., & Jones, S. A. (2018). Rapidly Progressive White Matter Involvement in Early Childhood: The Expanding Phenotype of Infantile Onset Pompe? JIMD Reports, 39, 55-62. https://doi.org/10.1007/8904_2017_46
Broomfield A, et al. Rapidly Progressive White Matter Involvement in Early Childhood: the Expanding Phenotype of Infantile Onset Pompe. JIMD Rep. 2018;39:55-62. PubMed PMID: 28726123.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapidly Progressive White Matter Involvement in Early Childhood: The Expanding Phenotype of Infantile Onset Pompe? AU - Broomfield,A, AU - Fletcher,J, AU - Hensman,P, AU - Wright,R, AU - Prunty,H, AU - Pavaine,J, AU - Jones,S A, Y1 - 2017/07/20/ PY - 2017/04/02/received PY - 2017/06/30/accepted PY - 2017/05/31/revised PY - 2017/7/21/pubmed PY - 2017/7/21/medline PY - 2017/7/21/entrez KW - CRIM negative KW - Enzyme replacement therapy KW - Glycogen KW - Infantile onset Pompe disease KW - Lysosomal storage KW - White matter disease SP - 55 EP - 62 JF - JIMD reports JO - JIMD Rep VL - 39 N2 - Glycogen accumulation in the central nervous system of patients with classical infantile onset Pompe disease (IOPD) has been a consistent finding on the few post-mortems performed. While delays in myelination and a possible reduction in processing speed have previously been noted, it has only been recently that the potential for clinically significant progressive white matter disease has been noted. The limited reports thus far published infer that in some IOPD patients, this manifests as intellectual decline in the second decade of life. We present a CRIM negative patient, immunomodulated with rituximab and methotrexate at birth, who despite an initial good clinical response to ERT, at the age of just under 4 years, presented with evolving spasticity in the lower limbs. The investigation of which revealed progressive central nervous system involvement. Given both the earlier onset of the symptoms and consanguineous familial pedigree, extensive biochemical and genetic investigation was undertaken to ensure no alternative pathology was elucidated. In light of these findings, we review the radiology and post-mortems of previous cases and discuss the potential mechanisms that may underlie this presentation. SN - 2192-8304 UR - https://www.unboundmedicine.com/medline/citation/28726123/Rapidly_Progressive_White_Matter_Involvement_in_Early_Childhood:_The_Expanding_Phenotype_of_Infantile_Onset_Pompe L2 - https://dx.doi.org/10.1007/8904_2017_46 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.