Skip to main content

Table 1 Characteristics of patients with SLC30A10, SLC39A14, and SLC39A8 mutations

From: Hypermanganesemia due to mutations in SLC39A14: further insights into Mn deposition in the central nervous system

Phenotypes SLC30A10 SLC39A14 SLC39A8
Early-onset dystonia, polycythemia and hepatopathy, adult-onset parkinsonism and spastic paraparesis Rapidly progressive childhood-onset parkinsonism-dystonia Type II congenital disorder of glycosylation with Leigh syndrome and autosomal recessive intellectual disability with cerebellar atrophy
Number of patients reported 39 10 12
References [16,17,18,19,20,21,22,23,24] [15] current paper [11, 12, 25]
First described in 2000 2016 2015
Age at onset, median (IQR) 7.1 (1–57 years) 15.8 (7–36 months) Birth to 1 year of age
Sex 20F/19M 6F/4M 8F/4M
Death and cause 4 death (3 cirrhosis-related complications and 1 pneumonia) 4 death (2 respiratory infections and 2 unknown cause) 1 death (infection)
Parental Consanguinity (N) 34 10 10
Main neurological signs and symptoms Focal and generalized dystonia, gait disturbances “cock-walk gait” and Parkinsonism Generalized dystonia and Parkinsonism Profound hypotonia
Other neurological signs and symptoms Central hypotonia, behavioral changes, developmental delay, dysphagia, ataxia, spastic paraparesis and sensory motor axonal polyneuropathy Spasticity, developmental delay, bulbar dysfunction Dystonia, opisthotonus, severe intellectual disability, strabismus, nystagmus, hearing impairment, apnea/hypopnea episodes, axonal neuropathy, generalized and myoclonic seizures and infantile spasm
Abnormal head growth / skull deformity Normal head circumference Microcephaly (N = 4), macrocephaly (N = 1),
Craniosynostosis (N = 1)
Normal head circumference, craniosynostosis in 1 patient
Blood Mn levels (nmol/L) Increased
3345.7 ± 2575.3 (RV: <320)
Increased
2898 ± 2532(RV: <320)
Decreased
16.4 ± 5.8 (RV: 5.3–40.8)
Urinary Mn levels Increased
11.3 ± 4.8 mcg/L (RV: 0.5–4)
Not reported (increased in our patient: 8.2 mcg/L; RV:0.4–0.9) Increased
56.5 ± 73.2 nmol/L (RV: 1.3–9.1)
Systemic involvement and others biochemical abnormalities Hepatopathy: Hepatomegaly in 14 patients, liver cirrhosis in 8 patients and increased transaminases in 41%: ALT: 107.1 ± 50.7 (RV <55)
Polycythemia in 21% of patients: haematocrit 52.8 ± 6.4% (RV: 34–40)
Not reported Dysmorphic featuresa, dwarfism with short limbs and scoliosis
Increased transaminases in 2 patient (AST: 441 UI/L (RV < 80), ALT: 102 and 113 UI/L (RV < 55)) and impaired blood coagulation 1 patient
High blood lactate (8.7 mmol/L) and CSF lactate (4.2 mmol/L) in 1 patient (RV: <1.9)
Abnormal glycosylation pattern in 7 patients
Brain MRI T1 W hyperintensity
Basal ganglia 38
Thalamus 20
Brainstem 13
Cerebellum 21
Pituitary gland 6
T1 W hyperintensity
Basal ganglia 10
Pituitary gland 8
Cerebral white matter 10
T2 W hyperintensity
Basal ganglia 2
Brainstem atrophy 1 Diffuse cerebral and cerebellar atrophy 4 Diffuse cerebellar atrophy 10
Frontal lobes atrophy 1
Genetics findings Missense 5
Stop gained 3
Deletion 11
Splicing 1
Missense 8
Stop gain 1
Deletion 1
Missense 14
Homozygous 37
Heterozygous 0
Homozygous 10
Heterozygous 0
Homozygous 10
Heterozygous 2
Chelation therapy Disodium calcium edetate, calcium ethylenediaminetetra-acetic acid, D-penicilamina and 2,3 mercaptosuccinic acid Disodium calcium edetate  
Other Treatments Iron oral supplementation 19
Zinc, vitamins C and D supplementation, manganese free-diet, L-dopa, pramiprexole and intratechal baclofen
  Galactose, manganese, CoQ10, thiamine, pyridoxine and glucocorticoid
  1. F Female, M Male, Mn Manganese, IQR Interquartile range, RV Reference values
  2. aDysmorphic features include a broad forehead, mid-face hypoplasia, small jaw, hirsutism, anteverted nostrils, thin lips and a smooth philtrum