Hypermanganesemia with dystonia, polycythemia and cirrhosis in 10 patients: Six novel SLC30A10 mutations and further phenotype delineation.
Clin Genet
; 93(4): 905-912, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-29193034
ABSTRACT
Biallelic mutations in the SLC30A10 gene cause an inborn error of Mn metabolism characterized by hypermanganesemia, polycythemia, early-onset dystonia, and liver cirrhosis (HMDPC). To date, only 14 families from various ethnic groups have been reported. Here, we describe 10 patients from 7 unrelated Egyptian families with HMDPC. Markedly elevated blood Mn levels, the characteristic basal ganglia hyperintensity on T1-weighted images, and variable degrees of extrapyramidal manifestations with or without liver disease were cardinal features in all patients. Eight patients presented with striking early diseased onset (≤2 years). Unexpectedly, early hepatic involvement before the neurological regression was noted in 3 patients. Mutational analysis of SLC30A10 gene revealed 6 novel homozygous mutations (c.77T > C (p.Leu26Pro), c.90C > G (p.Tyr30*), c.119A > C (p.Asp40Ala), c.122_124delCCT (p.Ser41del), c.780_782delCAT (p.Iso260del) and c.957 + 1G > C). Treatment using 2,3 dimercaptosuccinic acid as a manganese chelating agent showed satisfactory results with improvement of biochemical markers, hepatic manifestations and relative amelioration of the neurological symptoms. Our findings present a large cohort of patients with HMDPC from same ethnic group. The majority of our patients showed severe and early presentation with clear phenotypic variability among sibship. Moreover, we extend the phenotypic and mutational spectrum and emphasize the importance of early diagnosis and treatment of this potentially fatal disorder.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte de Catión
/
Hígado
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Enfermedades Metabólicas
Tipo de estudio:
Screening_studies
Límite:
Adolescent
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
País/Región como asunto:
Africa
Idioma:
En
Revista:
Clin Genet
Año:
2018
Tipo del documento:
Article
País de afiliación:
Egipto