Desmosterolosis (desmosterolosis) - Gen DHCR24.  

The desmosterolosis is a disease characterized mainly by neurological problems such as brain abnormalities and developmental delay. This disease could also cause other signs and symptoms such as delayed speech and motor skills, malformation of the corpus callosum and white matter loss, spasticity and arthrogryposis affecting hands and feet. Other features seen in some affected individuals include short stature, abnormal head size, either larger or smaller than normal, micrognathia, cleft palate, nystagmus, strabismus, heart defects and seizures.

The desmosterolosis is due to mutations in the gene DHCR24, located on the short arm of chromosome 1 (1p32.3). This gene encodes the reductase enzyme 24-dehydrocholesterol. This enzyme is involved in multiple pathways that produce cholesterol. Firstly, the 24-dehydrocholesterol reductase is involved in cholesterol synthesis by conversion of desmosterol lipid cholesterol. Moreover, 24 dehydrocholesterol reductase converts lanosterol lipid called lipid in another 24.25-dihydrolanosterol. The final product of both is cholesterol. Cholesterol is required for normal embryonic development and has important roles both before and after birth. It is an important component of cell membranes and myelin. In addition, cholesterol binds to certain proteins to activate the signaling pathway "hedgehog", which is critical for normal development of many parts of the body before birth. Additionally, cholesterol plays a role in the production of certain hormones and digestive acids.

They have been described at least seven mutations in the gene responsible for desmosterolosis DHCR24. These mutations change the amino acids 24-dehydrocholesterol reductase enzyme. As a result, the enzyme activity is reduced and the production of cholesterol as well. Without proper cholesterol, cell membranes are not formed properly and nerve cells are not protected by myelin, leading to the death of these cells. In addition, a decrease in cholesterol production has more serious before birth than during other periods of development due to the rapid increase occurring in the number of cells effects. Disruption in the normal formation of cells before birth abnormalities probably explains further development of desmosterolosis.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with desmosterolosis, by complete PCR amplification of the exons of the gene DHCR24, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).