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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