**5. Conclusion**

Inborn errors of cholesterol metabolism have provided many fundamental insights into normal cholesterol homeostasis and cell biology over several decades. These disorders have been viewed as discrete diseases with their own unique genetic, biochemical and cellular consequences that in turn cause the clinical spectrum of symptoms associated with each disease. There remain specific pre-squalene enzymatic defects to be characterised and many unanswered questions regarding the pathogenesis of the cholesterol biosynthesis defects. What has been surprising is that at least three cholesterol-related disorders (SLOS, NPC and TD) all share a common pathological inhibition of the NPC pathway. The precise mechanism that inhibits this pathway in SLOS and TD remains to be fully elucidated, but these findings are suggestive of novel therapeutic approaches to treating SLOS and TD using drugs that modify the cell biology of NPC such as miglustat. Whether other human diseases also involve NPC pathway dysfunction remains to be determined. Current investigation of this question may pave the way for novel approaches to therapy for diseases that currently lack effective treatments.

MA, mevalonic aciduria; HIDS, hyper IgD syndrome; SQSD, squalene synthase deficiency; LSS, lanosterol synthase deficiency; HEM, hydrops-ectopic calcification-moth-eaten; CHILD, congenital hemidysplasia with ichthyosiform erythroderma and limb defects; CDPX2, X-linked chondrodysplasia punctate 2; SLOS, Smith-Lemli-Opitz syndrome; DD, developmental delay; II, intellectual impairment; CHD, congenital heart defect; AR, autosomal recessive; XLD, X-linked dominant.

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*Human Cholesterol Biosynthesis Defects DOI: http://dx.doi.org/10.5772/intechopen.87150*

The authors have no COI to declare.

The authors thank Kevin Milo for proof reading and insightful comments in the

**Acknowledgements**

manuscript preparation.

**Conflict of interest**

**Author details**

Erin Anderson1

Brisbane, Australia

Australia

and David Coman1,2,3\*

2 Department of Metabolic Medicine Queensland Children's Hospital, Brisbane,

3 School of Medicine, Griffith University Gold Coast, University of Queensland

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: enquiries@drdavidcoman.com.au

1 Virtus Diagnostics, Brisbane, Australia

provided the original work is properly cited.

*Human Cholesterol Biosynthesis Defects DOI: http://dx.doi.org/10.5772/intechopen.87150*
