Adenylosuccinate Lyase Deficiency

Definition

Definition of Adenylosuccinate Lyase Deficiency
Adenylosuccinate lyase deficiency, also called adenylosuccinase deficiency, is a rare autosomal recessive metabolic disorder characterized by the appearance of succinylaminoimidazolecarboxamide riboside (SAICA riboside) and succinyladenosine (S-Ado) in cerebrospinal fluid, urine, and to a lesser extent in plasma.

These two succinylpurines are the dephosphorylated derivatives of SAICA ribotide (SAICAR) and adenylosuccinate (S-AMP), the two substrates of adenylosuccinate lyase (ASL), which catalyzes an important reaction in the de novo pathway of purine biosynthesis. ASL catalyzes two distinct reactions in the synthesis of purine nucleotides, both of which involve the ß-elimination of fumarate to produce either aminoimidazole carboxamide ribotide (AICAR) from SAICAR or adenosine monophosphate (AMP) from S-AMP.

Symptoms

Symptoms of Adenylosuccinate Lyase Deficiency
The signs, symptoms as well as the physical findings that are associated with ASLD greatly differ from one case to case. As a rule, most patients suffering from ASLD usually present with certain mix of neurological symptoms that include some of the following: autistic features, psychomotor retardation, epilepsy, muscle wasting as well as secondary feeding problems. While abnormal features may not be common, it can possibly occur including small head circumference, severe growth failure, flat occiput and low set ears, among others.

Causes

Causes of Adenylosuccinate Lyase Deficiency
It is still unclear whether ASLD and the pathological mechanisms are brought about by purine deficiency, perturbation of the pathway or toxicity of intermediates.

Diagnosis

Diagnosis of Adenylosuccinate Lyase Deficiency
Diagnostic tests for ADSL are usually based on the presence in cerebospinal fluid and urine samples that appear to contain AICA-riboside and S-Ado.

Treatment

Treatment of Adenylosuccinate Lyase Deficiency
Several patients, those that present early epilepsy usually die in infancy. Other patients, predominantly those with higher S-Ado/SAICA-riboside ratios tend to fare relatively well and usually reach adult age. The aim of the treatment is to replenish the decreased concentrations of adenine nucleotides in ADSL-deficient tissues. Some of these patients are treated with oral adenine for several months. More recently, there have been reports that the oral administration of D-ribose has effectively reduced frequency of seizure attacks as well as improve behavior.

Prognosis

Prognosis of Adenylosuccinate Lyase Deficiency
A patient with autistic features and mild psychomotor delay carries two novel mutations in this gene, E80D and D87E. The creation of a mouse model of this disease will be an important step in elucidating the in vivo mechanisms of the disease. Mice carrying mutations that cause ADSL deficiency in humans will be informative as to the effects of these mutations both during embryogenesis and on the brain, possibly leading to therapies for this disease in the future.

Prevention

Prevention of Adenylosuccinate Lyase Deficiency
Consult with your doctor.