National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Adenylosuccinase deficiency


Other Names:
Adenylosuccinate lyase deficiency; ADSL deficiency
Categories:
Adenylosuccinase deficiency impacts the way the body breaks down certain chemicals and results in damage to the nervous system. There are several types of adenylosuccinase deficiency. Symptoms vary greatly from person to person. In general, adenylosuccinase deficiency causes intellectual and movement disabilities, autistic features, epilepsy, low muscle tone, and feeding problems. In the most severe form of this condition, symptoms begin in infancy and death usually occurs in early childhood. Adenylosuccinase deficiency is caused by mutations in the ADSL gene and is inherited in an autosomal recessive fashion. It is diagnosed based on the clinical examination, imaging studies, laboratory tests, and confirmed by genetic testing. Treatment is focused on managing the symptoms, especially epilepsy.[1][2][3]
Last updated: 7/8/2020
The following list includes the most common signs and symptoms in people with adenylosuccinase deficiency. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms include:[3] 
  • Poor cognitive development
  • Severe motor delay 
  • Seizures
  • Low muscle tone
  • Autistic behaviors
Symptoms of adenylosuccinase deficiency tend to get worse over time. There are three types of adenylosuccinase deficiency. The most severe form is the fatal neonatal form in which symptoms are present in infancy. In the other forms, symptoms begin later in childhood. Less than 100 people have been reported with this condition and the severity of symptoms is different from person to person.[1][3][4]
Last updated: 7/8/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 42 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Absent speech
Absent speech development
Lack of language development
Lack of speech
No speech development
No speech or language development
Nonverbal
[ more ] 		0001344
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ] 		0000463
Brachycephaly
Short and broad skull
0000248
Flat occiput 0005469
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Hypointensity of cerebral white matter on MRI 0007103
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Long philtrum 0000343
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Microcephaly
Small head circumference
Reduced head circumference
Decreased size of skull
Decreased circumference of cranium
Abnormally small skull
[ more ] 		0000252
Prominent metopic ridge 0005487
Seizure 0001250
Severe global developmental delay 0011344
Short nose
Decreased length of nose
Shortened nose
[ more ] 		0003196
Smooth philtrum 0000319
Thin upper lip vermilion
Thin upper lip
0000219
5%-29% of people have these symptoms
Happy demeanor 0040082
Percent of people who have these symptoms is not available through HPO
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness
[ more ] 		0000718
Autism 0000717
Autosomal recessive inheritance 0000007
Brisk reflexes 0001348
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral atrophy
Degeneration of cerebrum
0002059
Cerebral hypomyelination 0006808
CNS hypomyelination 0003429
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
Gait ataxia
Inability to coordinate movements when walking
0002066
Global developmental delay 0001263
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth
[ more ] 		0001510
Hyperactivity
More active than typical
0000752
Inability to walk 0002540
Inappropriate laughter 0000748
Infantile onset
Onset in first year of life
Onset in infancy
[ more ] 		0003593
Myoclonus 0001336
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Opisthotonus 0002179
Poor eye contact 0000817
Self-mutilation
Deliberate self-harm
Self mutilation
[ more ] 		0000742
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ] 		0003202
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Wide mouth
Broad mouth
Large mouth
[ more ] 		0000154
Showing of 42 |
Last updated: 7/1/2020
Adenylosuccinate lyase deficiency occurs when the ADSL gene is not working correctly.[2][3]DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.
Last updated: 7/8/2020
Adenylosuccinase deficiency is inherited in an autosomal recessive pattern.[3] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must be altered to have the condition.
  
People with autosomal recessive conditions inherit one alteration from each of their parents. The parents, who each have one gene alteration, are known as carriers.  Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition. 
Last updated: 7/8/2020
Adenylosuccinase deficiency is diagnosed through a clinical exam, imaging studies, laboratory tests, and confirmed by genetic testing. People with this condition have two unusual chemicals present in the cerebral spinal fluid, urine and plasma.[1][3][4][5]
Last updated: 7/8/2020

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
Treatment of adenylosuccinate deficiency is focused on managing the symptoms.[1][3][4]

Specialists involved in the care of someone with adenylosuccinate deficiency may include:
  • Neurologist
  • Neonatalogist
  • Radiologist
Last updated: 7/8/2020
Less than 100 people with adenylosuccinase deficiency have been reported in the medical literature. One paper estimated that 1 in 1.25 million people may have this condition.[2][6]
Last updated: 7/8/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnoses include neurological disorders with intractable seizures and encephalopathy, and other inborn errors of purine and pyrimidine metabolism with neurological manifestations.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Autism Speaks organization has information about the many opportunities that are available for families who want to participate in autism research. Click on the link to learn more about the way families can participate.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Adenylosuccinase deficiency. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Adenylosuccinase deficiency. Click on the link to view a sample search on this topic.

Diagrams/Images

  • The Autism Speaks has developed a new Video Glossary, an innovative web-based tool designed to help parents and professionals learn more about the early red flags and diagnostic features of autism spectrum disorders (ASD). This glossary contains more than 150 video clips and is free of charge.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Adenylosuccinate lyase deficiency. National Organization for Rare Disorders (NORD). Updated 2010; https://rarediseases.org/rare-diseases/adenylosuccinate-lyase-deficiency.
  2. Mao X, Li K, Tang B, et al. Novel mutations in ADSL for Adenylosuccinate Lyase Deficiency identified by the combination of Trio-WES and constantly updated guidelines. Sci Rep. 2017; 7(1):1625. https://pubmed.ncbi.nlm.nih.gov/28487569.
  3. Jurecka A, Zikanova M, Kmoch S, Tylki-Szymanska A. Adenylosuccinate lyase deficiency. J Inherit Metab Dis. 2015; 38(2):231-242. https://pubmed.ncbi.nlm.nih.gov/25112391.
  4. Mastrangelo M, Alfonsi C, Screpanti I, et al. Broadening phenotype of adenylosuccinate lyase deficiency: A novel clinical pattern resembling neuronal ceroid lipofuscinosis. Mol Genet Metab Rep. 2019; 21:100502. https://pubmed.ncbi.nlm.nih.gov/31467849.
  5. Kayfan S, Yazdani RM, Castillo S, Wong K, Miller JH, Pfeifer CM. MRI findings of hypomyelination in adenylosuccinate lyase deficiency. Radiol Case Rep. 2018; 14(2):255-259. https://pubmed.ncbi.nlm.nih.gov/30510607.
  6. Ferreira CR. Prevalence of adenylosuccinate lyase deficiency based on aggregated exome data.. Mol Genet Metab Rep. 2017; 10:81-82. https://pubmed.ncbi.nlm.nih.gov/28127531.