1 December 2011
We read with great interest the recent report by Ortez et al. , “Undetectable levels of CSF amyloid-β (Aβ) peptide in a patient with 17β-hydroxysteroid dehydrogenase deficiency”. The authors claim that Aβ peptide was not detectable in the cerebrospinal fluid (CSF) of a mentally retarded patient. The dramatically reduced levels of amyloid-β peptide in CSF might indicate an alteration of amyloid-β protein precursor metabolism or trafficking in the patient’s brain. To our knowledge, thirteen of fourteen different types of 17β-hydroxy-steroid dehydrogenase have been discovered in human tissues . For example, 17β-hydroxysteroid dehydrogenase III deficiency  is a completely different disease from 17β-hydroxysteroid dehydrogenase X deficiency . The disease suffered by this patient should be specifically described as “17β-hydroxysteroid dehydrogenase X deficiency” rather than 17β-hydroxysteroid dehydrogenase deficiency—an all-inclusive term.
A variety of amyloid-β peptides including Aβ1-37, Aβ1-38, Aβ1-39, Aβ1-40, and Aβ1-42 are present in human CSF . However, data presented in this article (see Fig. 1 of Ref. 1) showed only the absence of a 44 kDa protein band in the patient’s CSF. As the authors emphasize, their finding points to a new direction for the study of Aβ metabolism, and it suggests that 17β-hydroxysteroid dehydrogenase X inhibitors might be candidates for Alzheimer’s disease therapy. Therefore, it is important that the absence of Aβ be firmly established. The masses of Aβ peptides lie in the range of 4300-4500 amu, and in several Western blotting procedures they migrate as monomers of apparent masses of about 4 kDa. Santa Cruz Biotechnology, Inc., the source of the antibody, claims that the band around 40 kDa revealed by their antibody is an oligomeric form of the 4 kDa peptide ; however, in experimental samples other explanations may account for the presence or absence of the band. We think that before one can accept that 17β-hydroxysteroid dehydrogenase X deficiency alters amyloid-β protein precursor metabolism or trafficking, the experiment must be repeated with other better characterized antibodies in other separation systems. For instance, a more sophisticated experimental procedure, namely quantitative urea-based Aβ-SDS-PAGE/immunoblot, could be employed . We hope this patient will be demonstrated not to be an anecdotal case of the reduction of Aβ peptide levels in CSF. The finding could be confirmed in other HSD10 deficiency patients carrying the same mutation (c.628C>T)  or different mutations [8,9] in the HSD17B10 gene.
Xue-Ying He1, David Miller2, Song-Yu Yang1
Departments of 1Neurochemistry and 2Molecular Biology, NYS Institute for Basic research in Developmental Disabilities, Staten Island, NY, USA
Acknowledgments: This work was supported in part by the NYS Office for People With Developmental Disabilities.
 Ortez C, Villar C, Fons C, Duarte ST, Perez A, Garcia-Villopia J, Ribes A, Ormazabal A, Casado M, Campistol J, Vilaseca MA, Garcia-Cazorla A (2011) Undetectable levels of CSF amyloid-β peptide in a patient with 17β-hydroxysteroid dehydrogenase deficiency. J Alzheimers Dis 27, 253-257.
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 Yang SY, He XY, Miller D (2011) Hydroxysteroid (17beta) dehydrogenase X in human health and disease. Mol Cell Endocrinol 343, 1-6.
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 Liu RT, Zou LB, Fu JY, Lu QJ (2010) Effects of liquiritigenin treatment on the learning and memory deficits induced by amyloid β-peptide (25-35) in rats.Behav Brain Res 210, 24-31.
 García-Villoria J, Navarro-Sastre A, Fons C, Pérez-Cerdá C, Baldellou A, Fuentes-Castelló MA, González I, Hernández-Gonzalez A, Fernández C, Campistol J, Delpiccolo C, Cortés N, Messeguer A, Briones P, Ribes A (2009) Study of patients and carriers with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency: difficulties in the diagnosis. Clin Biochem 1-2, 27-33.
 Seaver LH, He XY, Abe K, Cowan T, Enns GM. Sweetman L, Lee S, Malik M, Yang SY (2011) A novel mutation in the HSD17B10 gene of a 10-year-old boy with refractory epilepsy, chreoathetosis and learning disability. PLoS ONE 6, 11. e27348.
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We thank Dr. Xue-Ying He and
We thank Dr. Xue-Ying He and collaborators for their interesting observations, which add important information to our work.
Regarding the nomenclature of the disease, we agree that “17β-hydroxysteroid dehydrogenase X deficiency”, or “HSD10 deficiency” as an alternative name, is the specific disorder of this patient. Although the type of 17β-hydroxysteroid dehydrogenase is not detailed in the title, “HSD10 deficiency” as the specific disease of the patient is largely stated all over the text. In any case, we agree that it should have been useful to clarify it in the title.
On the other hand, we fully agree with Dr. He and collaborators about the necessity of analyzing other varieties of amyloid-β peptides in the cerebrospinal fluid (CSF) and to confirm the results by other more complex procedures. We are grateful indeed for these suggestions. Unfortunately the CSF volume from this patient that still remains in our laboratory is probably not enough to carry out these complementary experiments. Nevertheless, it would be extremely useful to collect more CSF in future patients in order to validate, and make more complete, the reported results.
Carlos Ortez1,2, Cristina Villar1,2, Carmen Fons1,2, Sofía T. Duarte1,3, Ana Pérez1,2, Judith García-Villoria2,4, Antonia Ribes2,4, Aida Ormazábal2,5, Mercedes Casado2,5, Jaume Campistol2,5, Maria Antonia Vilaseca2,5, Angels García-Cazorla1,2
Department of 1Neurology and 5Biochemistry, Hospital Sant Joan de Déu, Barcelona, Spain
2CIBER-ER (Biomedical Network Research Centre on Rare Diseases), Instituto de Salud Carlos III, Madrid, Spain
3Neuropaediatric Department, Hospital D. Estefânia, CHLC, EPE and CEDOC, Faculdade de Ciências Médicas da Universidade Nova de Lisboa, Portugal
4Sección de Errores Congénitos del Metabolismo (IBC), Servicio de Bioquímica y Genética Molecular, Hospital Clínic, Barcelona, Spain.