Autosomal-recessive iron deficiency anemia, dystonia and hypermanganesemia caused by new variant mutation of the manganese transporter gene SLC39A14

This inborn error of manganese metabolism has only recently been identified. A total of 28 affected individuals from ten families are known worldwide. Mutations in SLC39A14, encoding a Mn uptake transporter, have recently been recognized to cause excessive Mn concentrations in the blood which is believed to be neurotoxic and lead to a parkinsonian-like movement disorder caused by accumulation of Mn in the basal ganglia. We are reporting a new variant of SLC39A14 gene mutation (OMIM 608736 8p21.3) that has never been described in the literature so far. The index case is a 3-year-old female who was born at 30 weeks' gestation by emergency lower segment caesarean section, the second of twins, weighing 1.4 kg. Parents have a consanguineous marriage (first cousins) and have four healthy male children. She presented at 30 months of age with history of unsteady gait of 4 months duration and is progressively worsening. She became stiff and has lost all of her locomotor skills. Apart from low serum iron and iron deficiency anemia, her initial work up was unremarkable. T1-weighted MRI brain showed bilateral hyperintense signal in basal ganglia, mid-brain and pontine tegmentum giving rise to the characteristic eye-of-the-tiger sign. Genetic DNA evaluation (Whole Exome Sequencing WES) identified the homozygous missense variant c.1136.T in exon 7 of SLC39A14 gene which is associated with hypermanganesemia. Whole blood Mn was markedly raised at 150 nmol/L (8 mg/L) (normal 10 nmol/L, 0.7 mg/Bioscientia). This young girl has just started treatment with intravenous disodium calcium edetate and oral iron.