Neerja Gupta1, Zoheb B Kazi2, Sheela Nampoothiri3, Sujatha Jagdeesh4, Madhulika Kabra5, Ratna Dua Puri6, Mamta Muranjan7, Mani Kalaivani8, Catherine Rehder2, Deeksha Bali2, Ishwar C Verma6, Priya S Kishnani2. 1. Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. Electronic address: neerja17@gmail.com. 2. Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC. 3. Department of Pediatric Genetics, Amrita Institute of Medical Sciences, Kerala, India. 4. Department of Clinical Genetics & Genetic Counselling, Mediscan Systems, Chennai, India. 5. Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. 6. Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India. 7. Department of Pediatrics, King Edward Memorial Hospital, Mumbai, India. 8. Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
Abstract
OBJECTIVES: To evaluate the clinical and molecular spectrum, and factors affecting clinical outcome of patients in India diagnosed with infantile-onset Pompe disease (IOPD). STUDY DESIGN: In this multicenter, cross-sectional study, we evaluated the records of 77 patients with IOPD to analyze their clinical course, outcomes, and factors influencing the outcomes. RESULTS: Of the 77 patients with IOPD, phenotype data were available in 59; 46 (78%) had the classic phenotype. Overall, 58 of 77 (75%) and 19 of 77 (25%) patients were symptomatic before and after age 6 months, respectively. Alpha-glucosidase gene variant analysis available for 48 patients (96 alleles) showed missense variants in 49 alleles. Cross-reactive immunologic material (CRIM) status could be determined or predicted in 44 of 48 patients. In total, 32 of 44 patients (72%) were CRIM-positive, and 12 of 44 patients (27%) were CRIM-negative. Thirty-nine cases received enzyme-replacement therapy (ERT), alglucosidase alfa, and 38 patients never received ERT. Median age at initiation of ERT was 6.5 months. Response to ERT was better in babies who had CRIM-positive, non-classic IOPD. CONCLUSIONS: This study highlights the clinical spectrum of IOPD in India and provides an insight on various factors, such as undernutrition, feeding difficulties, and recurrent respiratory infection, as possible factors influencing clinical outcomes in these patients. The study also reiterates the importance of raising awareness among clinicians about the need for early diagnosis and timely treatment of IOPD.
OBJECTIVES: To evaluate the clinical and molecular spectrum, and factors affecting clinical outcome of patients in India diagnosed with infantile-onset Pompe disease (IOPD). STUDY DESIGN: In this multicenter, cross-sectional study, we evaluated the records of 77 patients with IOPD to analyze their clinical course, outcomes, and factors influencing the outcomes. RESULTS: Of the 77 patients with IOPD, phenotype data were available in 59; 46 (78%) had the classic phenotype. Overall, 58 of 77 (75%) and 19 of 77 (25%) patients were symptomatic before and after age 6 months, respectively. Alpha-glucosidase gene variant analysis available for 48 patients (96 alleles) showed missense variants in 49 alleles. Cross-reactive immunologic material (CRIM) status could be determined or predicted in 44 of 48 patients. In total, 32 of 44 patients (72%) were CRIM-positive, and 12 of 44 patients (27%) were CRIM-negative. Thirty-nine cases received enzyme-replacement therapy (ERT), alglucosidase alfa, and 38 patients never received ERT. Median age at initiation of ERT was 6.5 months. Response to ERT was better in babies who had CRIM-positive, non-classic IOPD. CONCLUSIONS: This study highlights the clinical spectrum of IOPD in India and provides an insight on various factors, such as undernutrition, feeding difficulties, and recurrent respiratory infection, as possible factors influencing clinical outcomes in these patients. The study also reiterates the importance of raising awareness among clinicians about the need for early diagnosis and timely treatment of IOPD.
Authors: Manuel A Viamonte; Stephanie L Filipp; Zara Zaidi; Matthew J Gurka; Barry J Byrne; Peter B Kang Journal: J Hum Genet Date: 2021-05-11 Impact factor: 3.172