Genetics of Adenylosuccinate Lyase Deficiency: Information for Patients

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Adenylosuccinate lyase deficiency is a rare inherited metabolic disorder that has four distinct types. It is also sometimes referred to as succinylpurinemic autism and adenylosuccinase deficiency. This disorder is best categorized as a disorder that affects purine nucleotides manufacturing through biosynthesis in the body. This disorder is rare so the genetics of adenylosuccinate lyase deficiency is still being studied. As of 2004, approximately 60 patients have been diagnosed with this disorder, however, it is believed that more patients have this disorder, but go undiagnosed because of a paucity in general screening and the heterogeneity of this disorder.

Genetics

From what is understood about the genetics of adenylosuccinate lyase deficiency, it is known that a deficiency in the nine and twelve enzymes result in seizures, mental retardation, and autistic behavior. Characteristics of this inherited metabolic disease include different degrees of psychomotor retardation, as well as the build up of succinyladenosine and dephosphorylated enzyme substrates 5-amino-4-imidazole-N-succinocarboxamide riboside in the body fluids. This genetic disorder is inherited in an autosomal recessive pattern.

Signs and Symptoms

Patients with this disorder may experience a variety of symptoms, such as epileptic seizures, growth retardation, autistic behavior, psychomotor retardation, behavioral disorders, and amyotrophy. Other possible signs and symptoms may include axial hypotonia with peripheral hypertonia, secondary feeding problems, muscle wasting, severe growth failure, brachycephaly, prominent metopic suture, small nose with anteverted nostrils, thin upper lip, small head circumference, flat occiput, intermittent divergent strabismus, long and smooth philtrum, and low set ears.

Diagnosis

When diagnosing this disorder, certain characteristics are looked for, such as the appearance of succinyladenosine and succinylaminoimidazolecarboxamide riboside in the urine, cerebrospinal fluid, and lesser in the plasma. Other diagnostic techniques may include those used to diagnose autistic disorders. Health care professionals should be evaluating all children under 24 months of age for behavior disorders and developmental delays. Developmental deficits to look for include:

By 12 months of age, the child is not pointing, babbling, or gesturing
By 24 months of age, no two-word spontaneous expression
By 18 months of age, no single words spoken
At any age, loss of any social or language skills

Other key behaviors to look for include:

Lack of affective reciprocity
Little evidence of pretend play
Lack of joint coordination
Limited imitation

Other testing may include:

Genetic testing
Medical history
Metabolic testing
Neurological evaluation
Psychological testing
Electrophysiologic testing

Treatment

Treatment most often involves treating the symptoms patients experience. For example, anti-seizure medications for epileptic seizures, vision correction methods for intermittent divergent strabismus, etc. Autistic disorder treatments may be used as well, such as behavioral therapy, speech therapy, etc. Physical therapy may also be beneficial.

Resources

Genetics Home Reference. (2010). ADSL. Retrieved on December 5, 2010 from Genetics Home Reference: https://ghr.nlm.nih.gov/gene/ADSL

National Organization for Rare Disorders. (2010). Adenylosuccinate Lyase Deficiency. Retrieved on December 5, 2010 from the National Organization for Rare Disorders: https://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Adenylosuccinate%20Lyase%20Deficiency