Adenilosuccinatoliasa deficiency (adenylosuccinate lyase deficiency) - Gen ADSL.

Adenilosuccinatoliasa deficiency is a neurological disorder that causes encephalopathy, psychomotor retardation and seizures. A feature that can help diagnose this disease is the presence of succinilaminoimidazol carboxamide riboside (SAICAR) and succiniladenosina (S-Ado) in body fluids. This disease is classified into three forms based on the severity of signs and symptoms.

The most severe form is the neonatal form. Signs and symptoms of this form can be detected before or during birth and may include growth problems during fetal development and microcephaly. Newborn infants with severe encephalopathy, which causes lack of movement, difficulty feeding and potentially fatal respiratory problems. Some affected infants develop seizures that do not improve with treatment. Because of the severity of encephalopathy, children with this form of the disease usually do not survive more than a few weeks after birth.

Deficiency type I adenilosuccinatoliasa, also known as the severe form, is the most common. Signs and symptoms of this form begin in the first months of life. Affected newborns have severe psychomotor retardation, hypotonia and microcephaly. Many affected children develop recurrent seizures that are difficult to treat, and show some autistic behaviors. In individuals with type II adenilosuccinatoliasa deficiency, also known as moderate or mild form, development is typically normal during the first years of life but then slows. Psychomotor retardation is considered mild or moderate. Some children with this form of the disease develop seizures and autistic behaviors.

Adenilosuccinatoliasa deficiency is due to mutations in the ADSL gene, located on the long arm of chromosome 22 (22q13.2). This gene encodes the enzyme adenylosuccinate lyase. This enzyme performs two steps in the process that synthesizes purine nucleotides. These nucleotides into the DNA, RNA and ATP molecules as serving as energy sources in the cell. Adenylosuccinate lyase and other enzymes involved in purine synthesis purinosoma form the complex proteins. This complex binds when there is a deficiency of purines or when a large amount of purines is needed, such as during cell division. As part of this complex, adenylosuccinate lyase converts a molecule called succinilaminoimidazol carboxamide riboside (SAICAR) in aminoimidazole carboxamide riboside (AICAR) and converts succiniladenosina monophosphate (SAMP) adenosine monophosphate (AMP).

There are more than 50 mutations in the gene responsible for ADSL adenilosuccinatoliasa deficiency. Most of the mutations involved in amino acid change adenilosuccinato lyase enzyme. Altered enzymes maintained between 2% and 20% of normal function, so are less able to form stable purinosomas. Reduced adenilosuccinato lyase function, possibly due to a deficiency of purinosomas leads to the accumulation of SAICAR and SAMP. These substances are converted, through a different reaction, in succinilaminoimidazol carboxamide riboside (SAICAR) and succiniladenosina (S-Ado). The detection of these substances in body fluids can aid in the diagnosis of disease. It is believed that S-Ado SAICAR and are toxic. Damage to brain tissue due to one or both of these substances is likely to lead to neurological problems that occur in adenilosuccinatoliasa deficiency. In addition, it is believed that the amount of SAICAR relative to S-Ado reflects the severity of illness. People with more than S-Ado SAICAR have encephalopathy and a severe psychomotor retardation.

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 deficiency adenilosuccinatoliasa, by complete PCR amplification of the exons of the gene ADSL 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).