Objective: To describe clinical, laboratory features and treatment outcomes among children with IH-Mn

Background: Inherited hypermanganesemia (IH-Mn) is a recently described neurogenetic condition caused by mutations in SLC30A10 and SLC39A14 genes. There is paucity of data on clinical spectrum and treatment outcomes in children with IH-Mn.

Method: We conducted a retrospective study from tertiary hospitals across India. We enrolled children between 1 month to 18 years of age with genetically confirmed/ clinically probable IH-Mn. Children with concurrent neurometabolic disorder and acquired brain injury were excluded. Clinical, laboratory findings, results of genetic testing and treatment details and outcomes scored on a Likert scale (no change, somewhat improved, marked improvement, normalization, mild/ moderate/ severe worsening) were analysed.

Results: We enrolled 27 children from 20 families (19 girls). 14 harboured SLC30A10 mutations; nine had SLC39A14 mutations. The SLC39A14 cohort had lower median age at onset [1.6 (IQR 0.7-5.8) years] compared to SLC30A10 cohort [2.9 (IQR 1.6-4.5) years]. The most frequent neurological features were dystonia (100%), gait abnormality (80.8%; n=21), falls (69.2%; n=18) and parkinsonism (61.5%; n=16). Eight demonstrated typical ‘cock-walk’ gait. Median blood Mn levels among SLC39A14 [60.5 (IQR 28.5-200.0) mcg/L] were higher than SLC30A10 [34.0 (23.9-100.0) mcg/L]. Median haemoglobin was higher in SLC30A10 [16.1 (IQR 15.2-17.5) g/dL] versus SLC39A14 cohort [11.7 (8.8-13.2) g/dL]. Hepatic involvement and polycythaemia were observed in SLC30A10 only. The SLC39A14 cohort had more severe disease evidenced by higher proportions of generalized dystonia and blood Mn levels. 26/27 children underwent chelation with disodium calcium edetate. Nine children demonstrated some improvement, two had marked improvement, three stabilized and one had normalization. One child had moderate worsening after some initial improvement. Children with SLC39A14 mutations had poorer response. Two children died and nine were lost to follow-up.

Conclusion: We found female predominance in children with IH-Mn. Children with SLC39A14 mutations were younger, had more severe disease and responded less favourably to chelation compared to SLC30A10. There is emerging need to better define management strategies for these children, especially in low resource settings.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-profile-and-treatment-outcomes-of-inherited-hypermanganesemia-among-27-indian-children-a-retrospective-multi-centric-study/