4.2 Article

Late onset Pompe Disease in India-Beyond the Caucasian phenotype

Journal

NEUROMUSCULAR DISORDERS
Volume 31, Issue 5, Pages 431-441

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nmd.2021.02.013

Keywords

Late onset Pompe disease; GAA variants; Cardiac; Severe phenotype; Splice site LOPD variant; India

Funding

  1. Indian Council of Medical Research - Department of Health Research grant [GIA/31 (vi) /2014DHR]
  2. MazumdarShaw research chair

Ask authors/readers for more resources

This study evaluated a cohort of Indian LOPD patients and found a more severe disease phenotype with higher prevalence of cardiac involvement compared to previous reports. The need to improve awareness and diagnosis of LOPD in India is emphasized.
We evaluated the clinical histories, motor and pulmonary functions, cardiac phenotypes and GAA genotypes of an Indian cohort of twenty patients with late onset Pompe disease (LOPD) in this multi-centre study. A mean age at onset of symptoms and diagnosis of 9.9 +/- 9.7 years and 15.8 +/- 12.1 years respectively was identified. All patients had lower extremity limb-girdle muscle weakness. Seven required ventilatory support and seven used mobility assists. Of the four who used both assists, two received ventilatory support prior to wheelchair use. Cardiac involvement was seen in eight patients with various combinations of left ventricular hypertrophy, tricuspid regurgitation, cardiomyopathy, dilated ventricles with biventricular dysfunction and aortic regurgitation. Amongst 20 biochemically diagnosed patients (low residual GAA enzyme activity) GAA genotypes of 19 patients identified homozygous variants in eight and compound heterozygous in 11: 27 missense, 3 nonsense, 2 initiator codon, 3 splice site and one deletion. Nine variants in 7 patients were novel. The leaky Caucasian, splice site LOPD variant, c.-32 -13T > G mutation was absent. This first study from India provides an insight into a more severe LOPD phenotype with earlier disease onset at 9.9 years compared to 33.3 years in Caucasian patients, and cardiac involvement more than previously reported. The need for improvement in awareness and diagnosis of LOPD in India is highlighted. (C) 2021 Elsevier B.V. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.2
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available