Marialuisa Quadri1, Mahesh Kamate2, Suvasini Sharma3, Simone Olgiati1, Josja Graafland1, Guido J Breedveld1, Indu Kori2, Virupaxi Hattiholi4, Puneet Jain3, Satinder Aneja3, Atin Kumar5, Parveen Gulati6, Medha Goel7, Bibek Talukdar7, Vincenzo Bonifati1. 1. Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. 2. Department of Paediatrics, KLE University's Jawaharlal Nehru J N Medical College, Belgaum, India. 3. Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India. 4. Department of Radiology, KLE University's Jawaharlal Nehru Medical College, Belgaum, India. 5. Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India. 6. Dr. Gulati Imaging Institute, New Delhi, India. 7. Department of Pediatrics, Chacha Nehru Bal Chikitsalaya, New Delhi, India.
Abstract
BACKGROUND: SLC30A10 mutations cause an autosomal recessive disorder, characterized by hypermanganesaemia, polycythemia, early-onset dystonia, paraparesis, or late-onset parkinsonism, and chronic liver disease. This is the first identified inborn error of Mn metabolism in humans, reported in 10 families thus far. METHODS: Methods for this study consisted of clinical examination, neuroimaging studies (MRI), serum dosages, and SLC30A10 genetic analysis. RESULTS: We describe early disease manifestations (including videos) in 5 previously unreported Indian children, carrying novel homozygous SLC30A10 mutations. Gait and speech disturbances, falls, dystonias, and central hypotonia were the presenting neurological features, starting within the first 5 years of life. All children also had severe hypermanganesemia, polycythemia, variable degree of liver disease, and marked brain MRI T1 hyperintensities. CONCLUSIONS: Our findings expand the mutational and clinical spectra of this recently recognized disorder. An early diagnosis is warranted, because treatment with manganese-chelating agents, iron supplementation, or their combination might improve symptoms and prevent progression of this otherwise potentially fatal disease.
BACKGROUND:SLC30A10 mutations cause an autosomal recessive disorder, characterized by hypermanganesaemia, polycythemia, early-onset dystonia, paraparesis, or late-onset parkinsonism, and chronic liver disease. This is the first identified inborn error of Mn metabolism in humans, reported in 10 families thus far. METHODS: Methods for this study consisted of clinical examination, neuroimaging studies (MRI), serum dosages, and SLC30A10 genetic analysis. RESULTS: We describe early disease manifestations (including videos) in 5 previously unreported Indian children, carrying novel homozygous SLC30A10 mutations. Gait and speech disturbances, falls, dystonias, and central hypotonia were the presenting neurological features, starting within the first 5 years of life. All children also had severe hypermanganesemia, polycythemia, variable degree of liver disease, and marked brain MRI T1 hyperintensities. CONCLUSIONS: Our findings expand the mutational and clinical spectra of this recently recognized disorder. An early diagnosis is warranted, because treatment with manganese-chelating agents, iron supplementation, or their combination might improve symptoms and prevent progression of this otherwise potentially fatal disease.
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