MtDNA depletion related rrm2b, encefalomiopática form with renal tubulopathy (rrm2b-related mitochondrial DNA depletion syndrome, renal tubulopathy With encephalomyopathic form) - Gen rrm2b

Syndrome mtDNA depletion related rrm2b, encefalomiopática form with renal tubulopathy (rrm2b-MDS), is a serious process beginning in childhood that affects multiple body systems. This process is associated with brain dysfunction, encephalomyopathy and, in most cases with renal tubulopathy.

Signs and symptoms associated with this process may include microcephaly; hypotonia can result in difficulty controlling the head movement, delayed development of motor skills, breathing difficulties (which can cause potentially fatal respiratory failure); Stunting and difficulty gaining weight. Additional clinical manifestations often include lactic acidosis; gastrointestinal dysmotility, which may result in problems with swallowing, vomiting and diarrhea, besides stunting; seizures; and sensorineural hearing loss. Because of the severity of signs and symptoms, people with rrm2b-MDS usually live only during early childhood.

As the name suggests, this process is due to mutations in the gene rrm2b (ribonucleotide reductase TP53 inducible regulatory subunit M2B) situated on the long arm of chromosome 8 (8q22.3), encoding the synthesis of a subunit termed p53R2, the ribonucleotide reductase protein (RNR). Two copies of the p53R2 subunit are attached to two copies of another protein called R1 to form RNR (R1 also can bind other small subunit, designated R2 to represent another form of RNR). The RNR performs a reaction leading to the synthesis of nucleotides. RNR containing p53R2 generates nucleotides used for the formation of mtDNA. MtDNA contains genes essential for oxidative phosphorylation process. Production nucleotides p53R2 also helps to maintain a normal amount of mtDNA in cells.

They have identified more than a dozen mutations in the gene responsible rrm2b development of mtDNA depletion rrm2b related syndrome, encefalomiopática form with renal tubulopathy (rrm2b-MDS). These mutations occur in both copies of the gene rrm2b, and result in a reduction of the activity or amount of RNR, probably alters the production of mtDNA nucleotides. A deficiency of nucleotides available for the production of mtDNA molecules causes mtDNA depletion and damage mitochondrial function in many different cell types. It is believed that impairment of oxidative phosphorylation underlies the signs and symptoms of the process.

This disease is inherited in an autosomal recessive pattern, which means that 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 syndrome mtDNA depletion related rrm2b, encefalomiopática form with renal tubulopathy, by complete PCR amplification of exons rrm2b 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).