About succinylpurinemic autism

What is succinylpurinemic autism?

Adenylosuccinate lyase deficiency (ASLD) is a rare, inherited metabolic disorder due to a lack of the enzyme adenylosuccinate lyase (ASL). The defect is characterized by the appearance of two unusual chemicals, succinylaminoimidazole carboxamide riboside (SAICA riboside) and succinyladenosine, in cerebrospinal fluid, in urine and, to a much smaller extent, in plasma. These compounds, which are never found in healthy individuals, are formed from the two natural compounds acted upon by the enzyme. The symptoms and the physical findings associated with ASLD vary greatly from case to case. As a rule, patients with ASLD present with a mix of neurological symptoms that usually will include some of the following: psychomotor retardation, autistic features, epilepsy, axial hypotonia with peripheral hypertonia, muscle wasting, and secondary feeding problems. Although abnormal physical features (dysmorphism) are not common, when they do occur they may include severe growth failure, small head circumference, brachycephaly, flat occiput, prominent metopic suture, intermittent divergent strabismus, small nose with anteverted nostrils, long and smooth philtrum, thin upper lip, and low set ears.

Adenylosuccinate lyase deficiency is categorized as a disorder of the manufacture of purine nucleotides from scratch (biosynthesis) in the body. Purine nucleotides play vital roles in the cells, particularly in the process of building up or breaking down complex body chemicals (intermediary metabolism) and in energy-transforming reactions. Moreover, they serve as building blocks of nucleic acids and thus participate in molecular mechanisms by which genetic information is stored. Just how the genetic and molecular mechanisms interact to generate the symptoms of ASLD is still debated.

What are the symptoms for succinylpurinemic autism?

Psychomotor delay symptom was found in the succinylpurinemic autism condition

Three categories of adenylosuccinate lyase deficiency have been recognized. The first is the fatal neonatal form, where babies have encephalopathy with lack of spontaneous movement, respiratory failure and intractable seizures. There may be some prenatal indications such as the fetus being small in size (IUGR), having a small head (microcephaly), a low level of fetal movement (hypokinesia) and a loss of fetal heart rate variability.

Adenylosuccinate lyase deficiency type I (ASLD-I), the severe childhood form, is only associated with neurological differences. These may include severe slowing of thought and movement (psychomotor impairment), epilepsy, Low muscle tone in the trunk of the body (axial hypotonia) with normal tendon reflexes and features associated with autism including absent or poor eye contact, stereotypies, tantrums, agitation and a tendency toward turning aggression onto oneself.

Patients with type II adenylosuccinate lyase deficiency (ASLD-II) have mild to moderate clinical features in comparison. They may have slight to moderate psychomotor impairment, show temporary changes in hearing and vision (transient auditory and visual contact disturbance), but do not have epilepsy.

The prognosis for ASLD is generally poor. Several patients, particularly those referred to as type I or with early onset of epilepsy, have died in early infancy. Others have died at around 10 years of age. In most patients, there is absent or minimal progression of psychomotor development and persistence of autistic behavior (if present), except for occasional improvement of eye contact. Nevertheless, some patients, particularly those referred to as type II, fare relatively well, and the oldest of these patients is over thirty.

What are the causes for succinylpurinemic autism?

ASLD is an autosomal recessive genetic disorder. Autosomal recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the abnormal gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

What are the treatments for succinylpurinemic autism?

Current treatments are available to control seizures, although drug resistance can occur. Studies have been done to identify treatments specific for ASLD (such as D-ribose, uridine and S-adenosyl-1-methionine), but these experimental treatments have not been proven to be beneficial.

What are the risk factors for succinylpurinemic autism?

All forms of adenylosuccinate lyase deficiency affect males and females in equal numbers. The age of onset and frequency is different between the different types. People with the fatal neonatal form and type I begin showing symptoms within the first few months of life. In type II, people begin showing symptoms within the first few years of life. Of known cases of ASLD, 5-10% of cases are the neonatal form, 70-80% are type I, and 15-20% are type II (Donti, 2016).

ASLD has been diagnosed in individuals from a number of countries (Australia, Belgium, Czech Republic, Colombia, Italy, France, Germany, Malaysia, Morocco, Netherlands, Norway, Poland, Portugal, Spain, Turkey, United Kingdom and the United States of America). The majority of individuals with this condition are in Belgium and Netherlands.

Is there a cure/medications for succinylpurinemic autism?

Succinylpurinemic autism can be treated through epilepsy control with anticonvulsive medications. In addition, the following choices are available:

  • Administration of D-ribose and Uridine: Only a few notifications of therapeutic considerations and attempts exist. Only two of them had some positive benefits (D-ribose and uridine administration). D-ribose injection has been used in a few ADSL patients to enhance the supply of phosphoribosyl pyrophosphate (PRPP) and encourage de novo purine synthesis.
  • The ketogenic diet: A ketogenic diet may be considered a legitimate therapeutic option in patients with intractable seizures during an ADSL deficiency course; however, due to the possibility of side effects that may occur during the diet, patients must undergo complete and systematic evaluations, including biochemical parameters of blood.
  • S-adenosyl-l-methionine: S-adenosyl-l-methionine (SAMe) is a possible treatment for ADSL insufficiency. There was no obvious response in urine metabolite levels or clinical indicators after 9 months of SAMe therapy.
  • Genetic consultation: Patients will benefit from a confirmed diagnosis when the chances for therapy or disease-altering management are not promising. The diagnosis allows the patient and family members to have access to organizations that would provide emotional support as well as practical guidance and help in dealing with the life changes that follow from disability. Accurate identification is critical so that families can obtain genetic counseling regarding risk recurrence and the likelihood of affected relatives who are asymptomatic or pre-symptomatic.
  • Treatment for epilepsy: The goal of epilepsy treatment is to control or at least reduce seizure frequency with minimum negative effects. Anticonvulsive medication (e.g., valproic acid, phenobarbital, carbamazepine, topiramate, levetiracetam, phenitoin, clobazam) is used depending on the kind of seizures. Patients with ADSL insufficiency frequently require polypharmacy, which includes the use of two or more anticonvulsants. Drug resistance is rather prevalent.

Psychomotor delay,Weak muscle tone, and microcephaly,Seizures,Autistic behaviors
Hypotonia,Seizures,Autistic behaviors
Valproic acid,Phenobarbital,Carbamazepine,Topiramate,Levetiracetam,Phenitoin,Clobazam

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