Hypomagnesemia with secondary hypocalcemia (Hypomagnesemia With hypocalcemia secondary) - Gen TRPM6
Hypomagnesemia with secondary hypocalcaemia is a hereditary disease caused by the body's inability to absorb and retain magnesium that is acquired through diet, leading to hypomagnesemia.
Hypomagnesemia impairs the function of the parathyroid glands. Normally, the parathyroid glands release the hormone that increases calcium concentration in blood when they are low. Magnesium is required for the production and release of parathyroid hormone, so that when magnesium levels are too low, not enough parathyroid hormone and calcium concentrations in the blood are reduced it occurs. Hypocalcemia is described as "secondary" because it occurs as a result of hypomagnesemia. Magnesium deficiency and calcium can lead to neurological problems that begin in childhood, including tetany and convulsions. If left untreated, hypomagnesemia with secondary hypocalcaemia can cause developmental delay, mental retardation, growth retardation and heart failure.
This process is due to mutations in the gene TRPM6, located on the long arm of chromosome 9 (9q21.13). This gene is predominantly expressed in kidney and colon, and encodes a protein that acts as a channel (TRPM6), allowing magnesium ions flow into cells. The channel may also allow small amounts of calcium ions to pass through the cells. Magnesium is involved in many cellular processes, including the production of cellular energy, maintaining nucleotides, encoding proteins, as well as growth and cell death. Furthermore, Mg2 + ions are needed for the production of parathyroid hormone that regulates calcium levels in the blood. Magnesium and calcium are also required for normal operation of motor neurons. The TRPM6 channel is in the membrane of epithelial cells lining the intestine, in the distal convoluted tubules, lung and testes in males. When the body needs Mg 2+ further, the TRPM6 channel allows it to be absorbed in the intestine and is filtered from fluids passing through the kidneys by the distal convoluted tubules. When the body has enough or too much Mg 2+, does not filter the channel TRPM6 Mg2 + ions from fluids but allows the ion release from the kidney cells to urine. The channel also helps regulate Ca 2+, but to a lesser degree.
There have been at least 38 mutations in the gene TRPM6 in people with hypomagnesemia with secondary hypocalcemia. These mutations result in a deficiency of functional protein. The channels TRPM6 nonfunctional prevent the absorption of Mg 2+ in the intestine and cause the elimination of excess Mg 2+ through urine. 2+ Mg deficiency in the blood affects the production of parathyroid hormone, and Ca 2+ concentrations in the blood are reduced. In addition, hypomagnesemia and hypocalcemia can disrupt many cellular processes and affect the function of motor neurons, leading to neurological problems and movement disorders characteristic of the disease. If the disease is not treated effectively and low Mg 2+ concentrations persist, signs and symptoms may worsen over time and can lead to premature death.
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 hypomagnesemia with secondary hypocalcemia, by complete PCR amplification of exons TRPM6 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).