Divyani Garg1, Sangeetha Yoganathan2, Uzma Shamim3, Kshitij Mankad4, Parveen Gulati5, Vincenzo Bonifati6, Abhijeet Botre7, Umesh Kalane8, Arushi Gahlot Saini9, Naveen Sankhyan9, Kavita Srivastava10, Vykuntaraju K Gowda11, Monica Juneja12, Mahesh Kamate13, Hansashree Padmanabha14, Debasis Panigrahi15, Shaila Pachapure16, Vrajesh Udani17, Atin Kumar18, Sanjay Pandey19, Maya Thomas2, Sumita Danda20, Shaikh Atif Iqbalahmed2, Annadurai Subramanian21, Harish Pemde22, Varinder Singh22, Mohammed Faruq3, Suvasini Sharma22. 1. Department of Neurology Lady Hardinge Medical College and Associated Hospitals New Delhi India. 2. Department of Neurological Sciences Christian Medical College Vellore India. 3. Genomics and Molecular Medicine CSIR-Institute of Genomics and Integrative Biology New Delhi India. 4. Department of Radiology Great Ormond Street Hospital NHS Foundation Trust London United Kingdom. 5. Department of Radiodiagnosis Doctor Gulati Imaging Institute New Delhi India. 6. Department of Clinical Genetics, Erasmus MC University Medical Center Rotterdam The Netherlands. 7. Department of Pediatrics, KEM Hospital Pune India. 8. Department of Pediatrics Deenanath Mangeshkar Hospital Pune India. 9. Department of Pediatrics, Advanced Pediatric Center Postgraduate Institute of Medical Education and Research Chandigarh India. 10. Department of Pediatrics Bharati Vidyapeeth Deemed University Medical College Pune India. 11. Division of Pediatric Neurology Indira Gandhi Institute of Child Health Bangalore India. 12. Department of Pediatrics, Lok Nayak Hospital, Maulana Azad Medical College University of Delhi New Delhi India. 13. Child Development and Pediatric Neurology Division, Department of Pediatrics KAHER's J N Medical College Belgaum India. 14. Department of Neurology National Institute of Mental Health and Neurosciences Bangalore India. 15. Department of Pediatrics Jagannath Hospital Bhubaneshwar India. 16. Department of Pediatrics, KAHER's J N Medical College Belgaum India. 17. Department of Child Neurology PD Hinduja Hospital and Medical Research Centre Mumbai India. 18. Department of Radiodiagnosis All India Institute of Medical Sciences New Delhi India. 19. Department of Neurology Govind Ballabh Pant Institute of Postgraduate medical education and research New Delhi India. 20. Department of Clinical Genetics Christian Medical College Vellore India. 21. Department of Pharmacy Services Christian Medical College Vellore India. 22. Department of Pediatrics (Neurology division) Lady Hardinge Medical College and Associated Hospitals New Delhi India.
Abstract
Background: Hypermanganesemia with dystonia 1 and 2 (HMNDYT1 and 2) are rare, inherited disorders of manganese transport. Objectives: We aimed to describe clinical, laboratory features, and outcomes among children with HMNDYT. Methods: We conducted a retrospective multicenter study involving tertiary centers across India. We enrolled children between 1 month to 18 years of age with genetically confirmed/clinically probable HMNDYT. Clinical, laboratory profile, genetic testing, treatment details, and outcomes scored by treating physicians on a Likert scale were recorded. Results: We enrolled 27 children (19 girls). Fourteen harbored SLC30A10 mutations; nine had SLC39A14 mutations. The SLC39A14 cohort had lower median age at onset (1.3 [interquartile range (IQR), 0.7-5.5] years) versus SLC30A10 cohort (2.0 [IQR, 1.5-5.1] years). The most frequent neurological features were dystonia (100%; n = 27), gait abnormality (77.7%; n = 21), falls (66.7%; n = 18), and parkinsonism (59.3%; n = 16). Median serum manganese (Mn) levels among SLC39A14 (44.9 [IQR, 27.3-147.7] mcg/L) cohort were higher than SLC30A10 (29.4 [17.1-42.0] mcg/L); median hemoglobin was higher in SLC30A10 (16.3 [IQR, 15.2-17.5] g/dL) versus SLC39A14 cohort (12.5 [8.8-13.2] g/dL). Hepatic involvement and polycythaemia were observed exclusively in SLC30A10 variants. A total of 26/27 children underwent chelation with disodium calcium edetate. Nine demonstrated some improvement, three stabilized, two had marked improvement, and one had normalization. Children with SLC39A14 mutations had poorer response. Two children died and nine were lost to follow-up. Conclusions: We found female predominance. Children with SLC39A14 mutations presented at younger age and responded less favorably to chelation compared to SLC30A10 mutations. There is emerging need to better define management strategies, especially in low resource settings.
Background: Hypermanganesemia with dystonia 1 and 2 (HMNDYT1 and 2) are rare, inherited disorders of manganese transport. Objectives: We aimed to describe clinical, laboratory features, and outcomes among children with HMNDYT. Methods: We conducted a retrospective multicenter study involving tertiary centers across India. We enrolled children between 1 month to 18 years of age with genetically confirmed/clinically probable HMNDYT. Clinical, laboratory profile, genetic testing, treatment details, and outcomes scored by treating physicians on a Likert scale were recorded. Results: We enrolled 27 children (19 girls). Fourteen harbored SLC30A10 mutations; nine had SLC39A14 mutations. The SLC39A14 cohort had lower median age at onset (1.3 [interquartile range (IQR), 0.7-5.5] years) versus SLC30A10 cohort (2.0 [IQR, 1.5-5.1] years). The most frequent neurological features were dystonia (100%; n = 27), gait abnormality (77.7%; n = 21), falls (66.7%; n = 18), and parkinsonism (59.3%; n = 16). Median serum manganese (Mn) levels among SLC39A14 (44.9 [IQR, 27.3-147.7] mcg/L) cohort were higher than SLC30A10 (29.4 [17.1-42.0] mcg/L); median hemoglobin was higher in SLC30A10 (16.3 [IQR, 15.2-17.5] g/dL) versus SLC39A14 cohort (12.5 [8.8-13.2] g/dL). Hepatic involvement and polycythaemia were observed exclusively in SLC30A10 variants. A total of 26/27 children underwent chelation with disodium calcium edetate. Nine demonstrated some improvement, three stabilized, two had marked improvement, and one had normalization. Children with SLC39A14 mutations had poorer response. Two children died and nine were lost to follow-up. Conclusions: We found female predominance. Children with SLC39A14 mutations presented at younger age and responded less favorably to chelation compared to SLC30A10 mutations. There is emerging need to better define management strategies, especially in low resource settings.
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