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 | [15] current paper | ||
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 |