Abstract
A boy presented at the age of 3.5 months with a developmental delay. He developed infantile spasms with hypsarrhytmia on EEG 1 month later. Additional symptoms were delayed visual development, asymmetrical hearing loss, hypotonia, and choreoathetoid movements. He also had some dysmorphic features and was vulnerable for infections. He was treated successively with vigabatrin, prednisolone, valproic acid, nitrazepam, and lamotrigine without a lasting clinical effect, but showed a treatment response to levetiracetam. Cerebral MRI showed hypoplasia of the corpus callosum and a mild delay in myelination. Further investigations including metabolic screening and glycosylation studies by transferrin isoelectric focusing were all considered to be normal. Whole-exome sequencing identified a de novo mutation in the ALG13 gene (c.320A>G, p.(Asn107Ser)). Mutations in this gene, which is located on the X-chromosome, are associated with congenital disorders of glycosylation type I (CDG-I). Mass spectrometric analysis of transferrin showed minor glycosylation abnormalities. The c.320A>G mutation in ALG13 has until now only been described in girls and was thought to be lethal for boys. All girls with this specific mutation presented with a similar phenotype of developmental delay and severe early onset epilepsy. In two girls glycosylation studies were performed which showed a normal glycosylation pattern. This is the first boy presenting with an epileptic encephalopathy caused by the c.320A>G mutation in the ALG13 gene. Since glycosylation studies are near-normal in patients with this mutation, the diagnosis of ALG13-CDG can be missed if genetic studies are not performed.
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Communicated by: Eva Morava, MD PhD
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Synopsis
The c.320A>G mutation in ALG13, which until now has only been described in girls, can also be a cause of ALG13-CDG with near-normal glycosylation studies in boys.
Author Contributions
Wienke H. Galama: Conception and design, literature review, drafted article, coordination of revisions, guarantor.
Sandra L. J. Verhaagen – van den Akker: Provided clinical data and drafted case report.
Dirk J. Lefeber: Provided glycosylation data, contribution of intellectual content and critical revision.
Ilse Feenstra: Provided genetic data, contribution of intellectual content and critical revision.
Aad Verrips: Conception and design, provided clinical data, contribution of intellectual content and critical revision.
Corresponding author: Wienke H. Galama.
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Wienke Galama declares that she has no conflict of interest.
Sandra Verhaagen – van den Akker declares that she has no conflict of interest.
Dirk Lefeber declares that he has no conflict of interest.
Ilse Feenstra declares that she has no conflict of interest.
Aad Verrips declares that he has no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study. Additional informed consent was obtained from all patients for which identifying information is included in this article.
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© 2017 Society for the Study of Inborn Errors of Metabolism (SSIEM)
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Galama, W.H., Verhaagen – van den Akker, S.L.J., Lefeber, D.J., Feenstra, I., Verrips, A. (2017). ALG13-CDG with Infantile Spasms in a Male Patient Due to a De Novo ALG13 Gene Mutation. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 40. JIMD Reports, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_53
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DOI: https://doi.org/10.1007/8904_2017_53
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