Sterol metabolism disorders and neurodevelopment-an update.

Abstract

Cholesterol has numerous quintessential functions in normal cell physiology, as well as in embryonic and postnatal development. It is a major component of cell membranes and myelin, and is a precursor of steroid hormones and bile acids. The development of the blood brain barrier likely around 12-18 weeks of human gestation makes the developing embryonic/fetal brain dependent on endogenous cholesterol synthesis. Known enzyme defects along the cholesterol biosynthetic pathway result in a host of neurodevelopmental and behavioral findings along with CNS structural anomalies. In this article, we review sterol synthesis disorders in the pre- and post-squalene pathway highlighting neurodevelopmental aspects that underlie the clinical presentations and course of Smith-Lemli-Opitz Syndrome (SLOS), mevalonic aciduria (MVA) or the milder version hyper-immunoglobulinemia D and periodic fever syndrome (HIDS), Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis (ABS1), congenital hemidysplasia with icthyosiform nevus and limb defects (CHILD) syndrome, CK syndrome, sterol C4 methyl oxidase (SC4MOL) deficiency, X-linked dominant chondrodysplasia punctata 2(CDPX2)/ Conradi Hunermann syndrome, lathosterolosis and desmosterolosis, We also discuss current controversies and share thoughts on future directions in the field.

• Authors: Shibani Kanungo, Neelkamal Soares, Miao He, Robert D Steiner
• Journal: Developmental disabilities research reviews (Dev Disabil Res Rev) Vol. 17 Issue 3 Pg. 197-210 ( 2013) ISSN: 1940-5529 [Electronic] United States
• PMID: 23798009 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

Chemical References

• Sterols
• Cholesterol
• Oxidoreductases Acting on CH-CH Group Donors

Topics

• Abnormalities, Multiple (metabolism)
• Animals
• Cholesterol (deficiency)
• Chondrodysplasia Punctata (metabolism)
• Genetic Diseases, X-Linked (metabolism)
• Humans
• Ichthyosiform Erythroderma, Congenital (metabolism)
• Limb Deformities, Congenital (metabolism)
• Lipid Metabolism, Inborn Errors (metabolism)
• Mevalonate Kinase Deficiency (enzymology, metabolism)
• Oxidoreductases Acting on CH-CH Group Donors (deficiency, metabolism)
• Smith-Lemli-Opitz Syndrome (enzymology, metabolism)
• Steroid Metabolism, Inborn Errors (metabolism)
• Sterols (metabolism)