TY - JOUR
T1 - Late onset Pompe Disease in India – Beyond the Caucasian phenotype
AU - Puri, Ratna Dua
AU - Setia, Nitika
AU - N, Vinu
AU - Jagadeesh, Sujatha
AU - Nampoothiri, Sheela
AU - Gupta, Neerja
AU - Muranjan, Mamta
AU - Bhat, Meenakshi
AU - Girisha, Katta M.
AU - Kabra, Madhulika
AU - Verma, Jyotsna
AU - Thomas, Divya C.
AU - Biji, Ishpreet
AU - Raja, Jayarekha
AU - Makkar, Ravinder
AU - Verma, Ishwar C.
AU - Kishnani, Priya S.
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.nmd.2021.02.013
DO - 10.1016/j.nmd.2021.02.013
M3 - Article
AN - SCOPUS:85102646254
SN - 0960-8966
VL - 31
SP - 431
EP - 441
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
IS - 5
ER -