Abstract
Hydroxysteroid 17-beta dehydrogenase type 10 (HSD10) deficiency (HSD10 disease) is a rare X-linked neurodegenerative condition caused by abnormalities in the HSD17B10 gene. A total of 10 mutations have been reported in the literature since 2000. Described phenotypes include a severe neonatal or progressive infantile form with hypotonia, choreoathetosis, seizures, cardiomyopathy, neurodegeneration, and death, as well as an attenuated form with variable regression. Here we present the second report of a c.194T>C (p.V65A) mutation in two half-brothers with a clinical phenotype characterized by neurodevelopmental delay, choreoathetosis, visual loss, cardiac findings, and behavioral abnormalities, with regressions now noted in the older sibling. Neither has experienced a metabolic crisis. Both of the siblings had normal tandem mass spectroscopy analysis of their newborn screening samples. The older brother’s phenotype may be complicated by the presence of a 3q29 microduplication. Diagnosis requires a high index of suspicion, as the characteristic urine organic acid pattern may escape detection. The exact pathogenic mechanism of disease remains to be elucidated, but may involve the non-dehydrogenase functionalities of the HSD10 protein. Our report highlights clinical features of two patients with the less fulminant phenotype associated with a V65A mutation, compares the reported phenotypes to date, and reviews recent findings regarding the potential pathophysiology of this condition.
Summary Sentence Hydroxysteroid 17-beta dehydrogenase type 10 (HSD10) disease (HSD10 disease) is a rare X-linked neurodegenerative condition with a variable clinical phenotype; diagnosis requires a high index of suspicion.
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Acknowledgements
We would like to thank Dr. Inderneel Sahai for her assistance with newborn blood spot (re)analysis.
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Communicated by: Johannes Häberle
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Neither this work nor any similar work has been submitted for previous or simultaneous publication. The above authors have substantially contributed to the analysis of these cases and the writing or revision of the included manuscript and agree to its submission for publication.
Annely Richardson – primary author, consolidated the case material for presentation, performed thorough literature review, wrote and edited the final manuscript for publication
Gerard T. Berry – provided metabolic genetics clinical consultation for these patients as well as expert analysis and critique of manuscript
Cheryl Garganta – provided expert analysis of clinical and laboratory data, and critique of the manuscript
Mary-Alice Abbott – primary geneticist of the patients described, initiated and supervised all aspects of the cases, data analysis, literature review, manuscript preparation, and final editing
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The patients and their guardians discussed provided their informed consent and permission to have their medical information discussed in this manuscript. Written documentation of verbal consent is available on request.
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Annely Richardson, Gerard T. Berry, Cheryl Garganta, and Mary-Alice Abbott declare that they have no conflict of interest.
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Richardson, A., Berry, G.T., Garganta, C., Abbott, MA. (2016). Hydroxysteroid 17-Beta Dehydrogenase Type 10 Disease in Siblings. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 32. JIMD Reports, vol 32. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_547
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DOI: https://doi.org/10.1007/8904_2016_547
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