Beta-ureidopropionase deficiency (Beta-ureidopropionase deficiency) - Gen UPB1.
Beta-deficiency ureidopropionase is a disturbance that generates an excessive amount of molecules N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine which are released into the urine.
Signs and symptoms associated with this disorder may include neurological problems, hypotonia, seizures, speech difficulties, developmental delay, mental retardation and autistic behaviors that affect communication and social interaction. Also, some people with this disorder have microcephaly, brain abnormalities and deterioration of the optic nerve can cause visual loss. In some people with beta-ureidopropionase deficiency, the disease does not generate neurological problems and can only be diagnosed by laboratory tests.
This process is due to mutations in the gene UPB1, located on the long arm of chromosome 22 (22q11.2). This gene encoding the enzyme beta-ureidopropionase, involved in degradation of pyrimidines, basic components of DNA and RNA. Specifically, the enzyme beta-ureidopropionase is involved in the last step that decomposes pyrimidines. This step converts the N-carbamyl-acid beta-aminoisobutyric to beta-aminoisobutyric acid and N-carbamyl decomposes-beta-alanine to beta-alanine, ammonia and carbon dioxide. It is believed that both the beta-aminoisobutyric acid and beta-alanine play roles in the nervous system. Beta-aminoisobutyric acid increases the production of a protein called leptin, which helps protect brain cells from damage caused by toxins, inflammation and other factors. Meanwhile, it is believed the beta-alanine is involved in synaptic transmission and control of the neurotransmitter dopamine.
They have identified at least 16 mutations in the gene UPB1 in persons deficient beta-ureidopropionase. These genetic changes reduce or eliminate the activity of the enzyme beta-ureidopropionase. The loss of enzyme function reduces the production of beta-aminoisobutyric acid and beta-alanine, and generates an excess of their precursor molecules, N-carbamyl-beta-aminoisobutyric acid and N-carbamyl-beta-alanine, which is eliminated in the urine. The reduced production of beta-aminoisobutyric acid and beta-alanine can affect their functions in the nervous system, leading to neurological problems in some people deficient beta-ureidopropionase. The extent of the reduction of enzyme activity caused by a genetic mutation UPB1, along with other genetic and environmental factors, can determine whether people deficient beta-ureidopropionase develop neurological problems and severity of these problems.
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 performed in IVAMI: in IVAMI perform detection of mutations associated with beta-ureidopropionase deficiency, by complete PCR amplification of exons UPB1 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).