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. 2022 Aug 12;9(7):886-899.
doi: 10.1002/mdc3.13516. eCollection 2022 Oct.

Clinical Profile and Treatment Outcomes of Hypermanganesemia with Dystonia 1 and 2 among 27 Indian Children

Divyani Garg  1 , Sangeetha Yoganathan  2 , Uzma Shamim  3 , Kshitij Mankad  4 , Parveen Gulati  5 , Vincenzo Bonifati  6 , Abhijeet Botre  7 , Umesh Kalane  8 , Arushi Gahlot Saini  9 , Naveen Sankhyan  9 , Kavita Srivastava  10 , Vykuntaraju K Gowda  11 , Monica Juneja  12 , Mahesh Kamate  13 , Hansashree Padmanabha  14 , Debasis Panigrahi  15 , Shaila Pachapure  16 , Vrajesh Udani  17 , Atin Kumar  18 , Sanjay Pandey  19 , Maya Thomas  2 , Sumita Danda  20 , Shaikh Atif Iqbalahmed  2 , Annadurai Subramanian  21 , Harish Pemde  22 , Varinder Singh  22 , Mohammed Faruq  3 , Suvasini Sharma  22
Affiliations

Clinical Profile and Treatment Outcomes of Hypermanganesemia with Dystonia 1 and 2 among 27 Indian Children

Divyani Garg et al. Mov Disord Clin Pract. .

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.

Keywords: cirrhosis; dystonia; manganese; parkinsonism.

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Figures

FIG. 1
FIG. 1
Pedigree chart of the largest family affected in our cohort.
FIG. 2
FIG. 2
Case F20. Top panel (a = axial T1, B = sagittal T1, C = FLAIR) shows presentation scans. Bottom panel shows corresponding post treatment images. Note the reduction in swelling and T1 shortening globally within the white matter, particularly within the globus pallidi (arrows) and the tegmentum and superior cerebellar peduncles. The axial FLAIR images show concomitant reduction in the hypointensity within the globus pallidi, but with some increased central focal hyperintensity (C‐arrow), which would be consistent with mild central pallidal gliosis.
See this image and copyright information in PMC

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