Clinical characteristics: SLC39A14 deficiency is characterized by evidence between ages six months and three years of delay or loss of motor developmental milestones (e.g., delayed walking, gait disturbance). Early in the disease course, children show axial hypotonia followed by dystonia, spasticity, dysarthria, bulbar dysfunction, and signs of parkinsonism including bradykinesia, hypomimia, and tremor. By the end of the first decade they develop severe, generalized, pharmaco-resistant dystonia, limb contractures, and scoliosis, and lose independent ambulation. Cognitive impairment appears to be less prominent than motor disability. Some affected children have succumbed in their first decade due to secondary complications such as respiratory infections.
Diagnosis/testing: The diagnosis of SLC39A14 deficiency is established in a proband with progressive dystonia-parkinsonism (often combined with other signs such as spasticity and parkinsonian features), characteristic neuroimaging findings, hypermanganesemia, and biallelic pathogenic variants in SLC39A14 on molecular genetic testing.
Management: Treatment of manifestations: Symptomatic treatment includes physiotherapy and orthopedic management to prevent contractures and maintain ambulation; use of adaptive aids (walker or wheelchair) for gait abnormalities; and use of assistive communication devices. Support by a speech and language/feeding specialist and nutritionist to assure adequate nutrition and to reduce the risk of aspiration. When an adequate oral diet can no longer be maintained, gastrostomy tube placement should be considered. Antispasticity medications (baclofen and botulinum toxin) and L-dopa have had limited success. While chelation therapy with intravenous administration of disodium calcium edetate early in the disease course shows promise, additional studies are warranted. Prevention of primary manifestations: Unknown, but disodium calcium edetate chelation therapy shows promise; additional studies are warranted. Surveillance: Routine monitoring of: Agents/circumstances to avoid: Evaluation of relatives at risk: Molecular genetic testing for the familial SLC39A14 pathogenic variants of apparently asymptomatic younger sibs of an affected individual allows early identification of sibs who would benefit from prompt initiation of treatment and preventive measures.
Genetic counseling: SLC39A14 deficiency is inherited in an autosomal recessive manner. Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the SLC39A14 pathogenic variants have been identified in an affected family member, carrier testing of at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.
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