Rare Genetic Diseases an Overview of Esmosterolosis

Desmosterolosis causes accumulation of the protein desmosterol in the blood, tissues and cultured cells. It is a disorder having to do with recessive chromosomes. A lack of the 3betahydroxysterol-delta24-reductase is the cause of this disease. Doctors find it in the cholesterol biosynthetic pathway. It is a rare genetic disease which causes inborn errors of metabolism. The adverse effects occur because the brain does not receive enough cholesterol to properly develop.

Confirmed phenotypes include mental retardation from microcephaly with agenesis of corpus callosum, and failure to survive, convulsions, involuntary eye movement and improper eye alignment, small jaw, and permanently bend fingers. A tightening of the hand tissue causes the mild to severe bend of the fingers making it very hard to use the hand.  

Previous studies revealed other symptoms such as: cleft palate, clubfoot, dysmorphism, mental and motor retardation, and speech development and death. An abnormally large or small head and deformed genitalia characterize the patient. In a case study, a three-year-old could not stand and only had a five-word vocabulary. Other medical problems did not present. As of June 2011, only two cases existed.

The disease has affected a family of Israeli Bedouins. Scientists studied four affected members in the family. Fourteen others in the family risk having the disease. Researchers used the four affected people, two fathers and two sons. Some in the family were carriers and some had the disease. The cholesterol levels of the two healthy males were normal. 300 other people of this ethnicity tested negative for the disease.

A similar disease that doctors have ruled out is homozygosity, where a patient has two identical forms of a particular gene. They tested the white matter with microsatellite markers derived from Marsheld maps. Desmosterolosis causes a reduction of white matter and partial of complete agenesis of corpus callosum. This occurs when the white matter connecting the two hemispheres in the brain does not develop.

In the mutation analysis, the amino acid FAD (flavin adenine dinucleotide) of the encoded protein substituted arginine for cysteine. Research associates missense mutations, where the single molecule in the structures of DNA and RNA is changed, with desmosterolosis.   

Through analysis of the sterols in dead babies after natural miscarriages, Clayton discovered desmosterolosis in 1996. In all studies the brain and genitals were deformed. The phenotypes compared positively with the SLOS syndrome known as the Smith – Lemli- Optiz syndrome. The difference between the two is the deficient enzyme in the cholesterol pathway.