ArticleJournal of inherited metabolic disease2017
A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders.
Article in Journal of inherited metabolic disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Targeted Therapies for Leigh Syndrome: Systematic Review and Steps Towards a 'Treatabolome'.Journal of neuromuscular diseases · 2021Pooled it
- Functional characterization of a novel ZIP8 variant causing impaired manganese homeostasis and congenital disorders of glycosylation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Functional screening of ZIP8 naturally occurring variants identifies pathogenic mutations and trafficking defects.The Journal of biological chemistry · 2026Article
- Repurposing the HMG-CoA reductase inhibitor atorvastatin for SRD5A3-congenital disorder of glycosylation.Communications medicine · 2026Article
- Manganese: biology, physiology and role in disease.Cell discovery · 2026Review
- Functional screening of ZIP8 naturally occurring variants identifies pathogenic mutations and trafficking defects.bioRxiv : the preprint server for biology · 2026Article
- Disorders Mimicking Wilson's Disease: Clinical, Biochemical, and Molecular Perspectives for Accurate Differential Diagnosis.Diagnostics (Basel, Switzerland) · 2026Review
- Cardiac oxidative damage and mitochondrial dysfunction induced by manganese deficiency are probably associated with the inhibition of the Nrf2 signaling pathway.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
- Early Diagnosis and Targeted Therapy in SLC39A8-Congenital Disorder of Glycosylation: A Case Report From Bulgaria.Cureus · 2026Article
- Allosteric modulation of the solute carrier transporter SLC39A8 potentiates manganese and cadmium uptake.The Journal of clinical investigation · 2025Article
- An iPSC-derived neuronal model reveals manganese's role in neuronal endocytosis, calcium flux and mitochondrial bioenergetics.iScience · 2025Article
- Systematic analysis of naturally occurring missense mutations in human manganese transporters: prediction and structural insights.bioRxiv : the preprint server for biology · 2025Article
- Manganese Neurotoxicity and Familial Disorders of Manganese Transport.Annals of the Child Neurology Society · 2025Review
- Consensus of Expert Opinion for the Diagnosis and Management of Hypermanganesaemia With Dystonia 1 and 2.Journal of inherited metabolic disease · 2025Article
- Improvement of Motor Function in SLC39A8-Related Ataxia Through Manganese Supplementation: A Therapeutic Insight.Movement disorders clinical practice · 2025Article
- Manganese Neurotoxicity: A Comprehensive Review of Pathophysiology and Inherited and Acquired Disorders.Journal of xenobiotics · 2025Review
- Human genetic variants in SLC39A8 impact uptake and steady-state metal levels within the cell.Life science alliance · 2025Article
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- Neuronal SLC39A8 deficiency impairs cerebellar development by altering manganese homeostasis.JCI insight · 2024Article
- The Manganese-Bone Connection: Investigating the Role of Manganese in Bone Health.Journal of clinical medicine · 2024Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SLC39A8 variants have recently been reported to cause a type II congenital disorder of glycosylation (CDG) in patients with intellectual disability and cerebellar atrophy. Here we report a novel SLC39A8 variant in siblings with features of Leigh-like mitochondrial disease. Two sisters born to consanguineous Lebanese parents had profound developmental delay, dystonia, seizures and failure to thrive. Brain MRI of both siblings identified bilateral basal ganglia hyperintensities on T2-weighted imaging and cerebral atrophy. CSF lactate was elevated in patient 1 and normal in patient 2. Respiratory chain enzymology was only performed on patient 1 and revealed complex IV and II + III activity was low in liver, with elevated complex I activity. Complex IV activity was borderline low in patient 1 muscle and pyruvate dehydrogenase activity was reduced. Whole genome sequencing identified a homozygous Chr4(GRCh37):g.103236869C>G; c.338G>C; p.(Cys113Ser) variant in SLC39A8, located in one of eight regions identified by homozygosity mapping. SLC39A8 encodes a manganese and zinc transporter which localises to the cell and mitochondrial membranes. Patient 2 blood and urine manganese levels were undetectably low. Transferrin electrophoresis of patient 2 serum revealed a type II CDG defect. Oral supplementation with galactose and uridine led to improvement of the transferrin isoform pattern within 14 days of treatment initiation. Oral manganese has only recently been added to the treatment. These results suggest SLC39A8 deficiency can cause both a type II CDG and Leigh-like syndrome, possibly via reduced activity of the manganese-dependent enzymes β-galactosyltransferase and mitochondrial manganese superoxide dismutase.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.