Abstract
Lathosterolosis is a rare defect of cholesterol synthesis. Only four previous cases have been reported, two of whom were siblings. We report a fifth patient, with a relatively mild phenotype. He presented at 5 years of age with bilateral posterior cataracts, which were managed with lensectomies and intraocular lens implants. He also had learning difficulties, with a full-scale IQ of 64 at 11 years of age. His head circumference is between the 0.4th and 2nd centiles, and he has mild hypotonia and subtle dysmorphism (a high-arched palate, anteverted nostrils, long philtrum and clinodactyly of toes). The diagnosis was established after sequencing a panel of genes associated with cataracts, which revealed compound heterozygous SC5D mutations: c.479C>G p.(Pro160Arg) and c.630C>A p.(Asp210Glu). The plasma lathosterol concentration was markedly raised at 219.8 μmol/L (control range 0.53–16.0), confirming the diagnosis. The c.630C>A p.(Asp210Glu) mutation has been reported in one previous patient, who also had a relatively mild phenotype (Ho et al., JIMD Rep 12:129–134, 2014). The mutation leads to a relatively conservative amino acid substitution, consistent with some residual enzyme activity. Our patient’s family did not notice any benefit from treatment with simvastatin. In summary, milder patients with lathosterolosis may present with learning difficulties, cataracts and very subtle dysmorphism. The diagnosis will be missed unless plasma sterols are analysed or relevant genes sequenced.
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Acknowledgements
Next-generation sequencing was supported by Fight for Sight UK (grant no. 1831). RLT is supported by a Medical Research Council/UK Research and Innovation Skills Development Fellowship (Ref: MR/R024952/1).
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Communicated by: Nancy Braverman, M.D., M.Sc.
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Contributions of Individual Authors
Drs. Anderson and Morris managed the patient and wrote the case report. Dr. Taylor undertook the next-generation sequencing, and Professors Clayton-Smith and Clayton confirmed the diagnosis clinically and by sterol analysis, respectively. Drs Rust and Ashworth undertook psychological assessment and ophthalmological management, respectively. All authors critically reviewed the manuscript.
Dr. Andrew Morris is the corresponding author and serves as guarantor.
Competing Interest Statement
Drs. Anderson, Rust, Ashworth, Taylor and Morris and Professors Clayton-Smith and Clayton declare that they have no conflict of interest.
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The patient’s parents have given written consent for publication. Ethical Committee approval is not needed for this case report.
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© 2018 Society for the Study of Inborn Errors of Metabolism (SSIEM)
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Anderson, R. et al. (2018). Lathosterolosis: A Relatively Mild Case with Cataracts and Learning Difficulties. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 44. JIMD Reports, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2018_127
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DOI: https://doi.org/10.1007/8904_2018_127
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