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

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 mutations; nine had mutations. The cohort had lower median age at onset (1.3 [interquartile range (IQR), 0.7-5.5] years) versus 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 (44.9 [IQR, 27.3-147.7] mcg/L) cohort were higher than (29.4 [17.1-42.0] mcg/L); median hemoglobin was higher in (16.3 [IQR, 15.2-17.5] g/dL) versus cohort (12.5 [8.8-13.2] g/dL). Hepatic involvement and polycythaemia were observed exclusively in 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 mutations had poorer response. Two children died and nine were lost to follow-up.

Conclusions: We found female predominance. Children with mutations presented at younger age and responded less favorably to chelation compared to mutations. There is emerging need to better define management strategies, especially in low resource settings.