Pyridoxal 5'-phosphate-dependent epilepsy - Gen PNPO.

The pyridoxal 5'-phosphate epilepsy is dependent alteration involving seizures that begin shortly after birth or, in some cases, before birth. Often associated signs and symptoms involve myoclonus, abnormal eye movements and seizures. Most newborns are born prematurely and may have lactic acidosis can be potentially lethal. In addition, some children have a slow heart rate and lack of oxygen during birth.

Anticonvulsant drugs, which are generally administered to control seizures, are not effective in persons with epilepsy pyridoxal 5'-phosphate-dependent. Instead, people with this type of epilepsy are treated medically with large daily doses of pyridoxal 5'-phosphate (a form of vitamin B6). If left untreated, people with this disorder may develop encephalopathy, which can lead to death. Although seizures can be controlled with pyridoxal 5'-phosphate can be present neurological problems such as developmental delay and learning disorders.

This process is due to mutations in the gene PNPO, located on the long arm of chromosome 17 (17q21.32). This gene encodes an enzyme called pyridoxine 5'-phosphate oxidase. This enzyme is involved in the metabolism of vitamin B6. Specifically, chemically it modified two forms of vitamin B6 derivative food (pyridoxine and pyridoxamine) to form pyridoxal 5'-phosphate (PLP). PLP is the active form of vitamin B6 and is necessary for many processes in the body, including the metabolism of proteins and neurotransmitters coding. Oxidase pyridoxine 5'-phosphate is expressed in cells throughout the body, with highest concentrations in liver.

They have identified at least seven mutations in the gene PNPO in people with epilepsy pyridoxal 5'-phosphate-dependent. Most of these mutations change the amino acid pyridoxine 5'-phosphate oxidase, impairing their function. The resulting enzyme can not effectively metabolize pyridoxine and pyridoxamine to produce PLP. A shortage of PLP can disrupt the function of many other proteins and enzymes they need PLP. It is unclear how the lack of PLP affects the brain and leads to seizures that are characteristic of this disease.

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 epilepsy pyridoxal 5'-phosphate-dependent, by complete PCR amplification of exons PNPO 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).