Myoclonus and renal failure syndrome ..., (Action myoclonus-renal failure syndrome) - Gen SCARB2  

Myoclonus syndrome and renal failure (AMRF) is a process which, as its name suggests, is characterized by episodes of myoclonus and often kidney disease. Although the name of the disease refers to kidney disease, not all those affected have problems with kidney function.

Movement problems associated with AMRF syndrome usually begin with trembling fingers and hands that occur at rest and are most noticeable when the person tries to make small movements, such as writing. Over time, the tremors may affect other parts of the body such as the head, torso, legs and tongue. These tremors progress to myoclonic jerks, which can be triggered by voluntary movements or the intention to move. These myoclonic jerks usually occur in the torso, the upper and lower limbs and the face, particularly the muscles around the mouth and the eyelids. Certain factors such as anxiety, excitement, stress or exhaustion can worsen myoclonus. Some affected individuals develop seizures, peripheral neuropathy and loss of hearing due to abnormalities in the inner ear. Seizures or severe myoclonus can be potentially fatal. Some individuals with myoclonus and renal failure (AMRF) syndrome also suffer from kidney problems. When problems occur in the kidneys, one of the first manifestations is proteinuria. Kidney function worsens over time, until the kidneys are no longer able to filter fluids and waste products from the body effectively, leading to end stage renal disease.

AMRF syndrome symptoms usually begin between 15 and 25 years, but may appear in younger or older ages. The age of onset and disease progression can vary, even among members of the same family. Any movement problems or kidney disease may occur first, or you can start at the same time. Most people survive 7 to 15 years after symptoms appear.

The AMRF syndrome is due to mutations in the SCARB2 (scavenger receptor class B member 2) gene, located on the long arm of chromosome 4 (4q21.1). This gene encodes the LIMP-2 protein, carrying a beta-glucocerebrosidase enzyme called lysosomes. In the lysosomes, beta-glucocerebrosidase degrades a fat substance known as glucocerebrosidase. LIMP-2 protein remains in the lysosome after transporting beta-glucocerebrosidase and is important for the stability of these structures. LIMP-2 protein has additional functions outside the lysosome. In the heart, the protein is at intercalated disks, which connect individual heart muscle cells to form strong fibers. LIMP-2 protein appears to play a role when the heart muscle is abnormally enlarged and has to work harder than normal, although its exact function is unclear. LIMP-2 protein is sometimes in the outer membrane surrounding the cell. Certain viruses can join LIMP-2, allowing them to enter and infect the cell. In particular enterovirus 71 and certain strains of coxsackievirus (A7, A14 and A16), using LIMP2 protein, causing a viral infection known as syndrome glosopeda or hands, feet and mouth.

At least 20 mutations in the gene have been associated SCARB2 with myoclonus syndrome and renal failure (AMRF). These genetic changes lead to the synthesis of an altered protein LIMP-2 which is caught in the endoplasmic reticulum and can not reach the lysosome. As a result, the movement of beta-glucocerebrosidase to lysosomes deteriorates. It is believed that beta-glucocerebrosidase deficiency in these structures contribute to the signs and symptoms of AMRF syndrome, although the mechanism is unclear. It is working to understand why some people with gene mutations SCARB2 have kidney problems and others do not.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations that 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 performed in IVAMI: in IVAMI perform detection of mutations associated with myoclonus syndrome and renal failure (AMRF), by complete PCR amplification of exons SCARB2 gene, 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).