Asparagine synthetase deficiency – ASNS gene
Asparagine synthetase deficiency (also known as asparagine metabolism disorder or ASNS deficiency -ASNSD-) is a pathology that causes neurological problems shortly after birth. The signs and symptoms related to this process include microcephaly, atrophy of brain tissue, psychomotor delay and/or developmental regression, hyperreflexia and hypotonia. Muscle problems get worse during childhood and lead to muscle stiffness, uncontrolled movements and, ultimately, spastic quadriplegia. In addition, many individuals with asparagine synthetase deficiency suffer from recurrent convulsions of the tonic-clonic, myoclonic and / or tonic types; hyperekplexia (exaggerated startle response) to unexpected stimuli; and cortical blindness.
This process is due to mutations in the ASNS gene (asparagine synthetase-glutamine-hydrolyzing), located on the long arm of chromosome 7 (7q21.3), which encodes the enzyme asparagine synthetase. This enzyme is found in all cells of the body, producing the amino acid asparagine from aspartic acid. Glutamine is another amino acid that participates in the process, becoming glutamic acid. Asparagine synthetase is believed to help maintain homeostasis or balance of these four amino acids in the body. Asparagine is necessary to produce many proteins, but it also performs other functions, including the decomposition of toxic ammonia inside cells, the modification of proteins and the production of a neurotransmitter.
At least 15 mutations in the ASNS gene have been identified in individuals with asparagine synthetase deficiency. In most cases, these mutations replace the individual amino acids in the enzyme, which results in enzymes with little or no function. Asparagine from the diet probably compensates for the inability of the enzyme to produce this amino acid in the cells. However, because asparagine cannot cross the blood-brain barrier, brain cells in people with asparagine synthetase deficiency have a deficiency of this amino acid. The lack of asparagine in the development of brain cells results in poor brain development and serious neurological problems. It is not known if glutamic acid deficiency or glutamine accumulation participates in the signs and symptoms of this condition.
This disease is inherited with an autosomal recessive pattern, which means that both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Asparagine synthetase deficiency, by means of the complete PCR amplification of the exons of the ASNS gene, and its subsequent sequencing.
Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).