Dilated cardiomyopathy with ataxia syndrome ... (ataxia syndrome Dilated cardiomyopathy With) - Gen DNAJC19.

Syndrome Dilated cardiomyopathy with ataxia (DCMA) is an inherited disorder characterized by cardiac problems, movement difficulties and other features that affect multiple organ systems.

From childhood, most people with DCMA syndrome develop dilated cardiomyopathy, making it difficult for the heart to pump blood efficiently. Some affected individuals also have long QT syndrome, which causes the heart muscle requires more time than usual to recharge between beats. Arrhythmia can cause syncope or cardiac arrest and sudden death. Rarely, heart problems improve with time. However, in most cases of DCMA syndrome, affected individuals do not survive beyond infancy due to heart failure. A small percentage of people with DCMA syndrome have no heart problems. Around 2 years of age, affected children have ataxia. These movement problems can lead to delayed motor skills such as getting up and walking, but most older children with DCMA syndrome can walk without support. In addition to heart problems and difficulties of movement, most people grow slowly before and after birth, leading to short stature. In addition, many affected individuals have mild intellectual disabilities.

Other signs and symptoms may include additional cryptorchidism or hypospadias in males, microcytic anemia, hepatic steatosis and optic nerve atrophy. Furthermore, DCMA syndrome is one of a group of metabolic disorders which can be diagnosed by the presence of higher concentrations of 3-methylglutaconic aciduria and 3-methylglutaric in urine.

This process is due to mutations in the gene DNAJC19, located on the long arm of chromosome 3 (3q26.33). This gene encodes a protein found in the mitochondria. Although the exact function of the protein is not clear, it is believed to help the transport of other proteins inside and outside of mitochondria. Furthermore, DNAJC19 protein can also aid in the assembly and disassembly of certain proteins correct.

They have been described at least two mutations in the gene DNAJC19 leading to dilated cardiomyopathy with ataxia (DCMA) syndrome. These mutations lead to an abnormally short coding protein with altered function. Dariusleut Hutterite population in Canada, where DCMA syndrome is seen most often, the disease is due to IVS3-1G> C mutation leading to a disruption in protein coding DNAJC19, resulting in the elimination of a portion of the protein. It is likely to DNAJC19 functional protein deficiency alters protein transport inside and outside the mitochondria. When too many or too few proteins move inside and outside the mitochondria it can be reduced energy production and mitochondrial survival. Tissues that have high energy demands, such as heart and brain, are particularly susceptible to decreased cellular energy production. This loss of cellular energy probably damages these and other tissues, leading to heart problems, movement difficulties, and other features of the DCMA syndrome.

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 dilated cardiomyopathy with ataxia (DCMA) syndrome by complete PCR amplification of the exons of the gene DNAJC19, 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).