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Genet Med. 2018 Feb;20(2):259-268. doi: 10.1038/gim.2017.106. Epub 2017 Jul 27.

SLC39A8 deficiency: biochemical correction and major clinical improvement by manganese therapy.

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Klinik und Poliklinik für Kinder- und Jugendmedizin-Allgemeine Pädiatrie, Universitätsklinikum Münster, Münster, Germany.
Centrum für Laboratoriumsmedizin, Universitätsklinikum Münster, Münster, Germany.
Sozialpädiatrisches Zentrum, Johannes-Wessling-Klinikum, Minden, Germany.
Klinik für Kinder- und Jugendmedizin, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.


PurposeSLC39A8 deficiency is a severe inborn error of metabolism that is caused by impaired function of manganese metabolism in humans. Mutations in SLC39A8 lead to impaired function of the manganese transporter ZIP8 and thus manganese deficiency. Due to the important role of Mn2+ as a cofactor for a variety of enzymes, the resulting phenotype is complex and severe. The manganese-dependence of β-1,4-galactosyltransferases leads to secondary hypoglycosylation, making SLC39A8 deficiency both a disorder of trace element metabolism and a congenital disorder of glycosylation. Some hypoglycosylation disorders have previously been treated with galactose administration. The development of an effective treatment of the disorder by high-dose manganese substitution aims at correcting biochemical, and hopefully, clinical abnormalities.MethodsTwo SCL39A8 deficient patients were treated with 15 and 20 mg MnSO4/kg bodyweight per day. Glycosylation and blood manganese were monitored closely. In addition, magnetic resonance imaging was performed to detect potential toxic effects of manganese.ResultsAll measured enzyme dysfunctions resolved completely and considerable clinical improvement regarding motor abilities, hearing, and other neurological manifestations was observed.ConclusionHigh-dose manganese substitution was effective in two patients with SLC39A8 deficiency. Close therapy monitoring by glycosylation assays and blood manganese measurements is necessary to prevent manganese toxicity.

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