Rare Genetic Diseases an Overview of Desmosterolosis

As the name suggest, desmosterolosis is a rare genetic disorder which has been documented in only few instances as a medical disorder. This has lead to a vacuum of knowledge in relation to this disease although the several cases that have been presented can give us a clue as to what this disease is all about.

What is the underlying pathology behind desmosterolosis?

The underlying pathological phenomenon in desmosterolosis is the disruption to the normal process of cholesterol metabolism. Thus, in other words, desmosterolosis can also be classified as a ‘metabolic disease’. At the same time, the metabolic product that becomes highlighted in this disease is the cholesterol precursor, desmosterol. Therefore, detection of its significantly high levels in the blood, tissues as well as on cultured cells gives the best clue in diagnosing desmosterolosis.

What contributes towards raised desmosterol?

Researchers believe that the occurrence of desmosterolosis is the result of a genetic mutation taking place in the gene which codes for the production of DHCR24 enzyme. These mutations will be inherited as autosomal recessive. Being an oxydoreductase enzyme in the cholesterol metabolism pathway, its absence can cause a significant deviation on the final outcome of the pathway and therefore accumulate desmosterol.

What is the basis for clinical manifestations?

Before going into the clinical manifestations of this disease, it is important to understand the usefulness of having a proper metabolism of cholesterol in the body. According to scientists, cholesterol is essential for the development of the brain and it directly affects the synaptogenesis or the building of linkages between the neurons. Cholesterol also contributes to the formation of most of the steroids including certain hormones and enzymes in the body. As such, it has the ability to affect various signaling pathways of which some are responsible for brain development, and patterning.

What are the clinical manifestations of desmosterolosis?

Thus, the clinical manifestations of this disease would be apparent in the newborns and these manifestations can include, congenital hydrocephalus, mild arthrogryposis, and dysmorphic facial features. Further to this, high resolution imaging techniques of the brain should also reveal certain other changes such as thickening of the tectum and massa intermedia, dysplastic cerebrum…etc.

What are the biochemical markers to detect this disease?

However, with all the clinical findings and imaging features, it is the blood chemical studies that would ultimately pin point the diagnosis. An elevated level of desmosterol and enzyme activity studies related to deficient DHCR24 will strengthen the clinical diagnosis.


Although the diagnosis of desmosterolosis can be made on these grounds, lack of clinical material and knowledge hinders the development of diagnostic standards and any therapeutic procedures to support the affected babies. However, if such standards and procedures exist, the number of desmosterolosis cases detected in the world could be much higher than the figures that the clinical community has seen so far.