Rare Gastroenterology News

Disease Profile

Adenylosuccinase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

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ICD-10

E79.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Adenylosuccinate lyase deficiency; ADSL deficiency

Categories

Congenital and Genetic Diseases; Metabolic disorders; Nervous System Diseases

Summary

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 occurs due to a ADSL gene that is not working correctly 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]

Symptoms

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] 

  • Intellectual disability
  • 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]

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.

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
Decreased circumference of cranium
Abnormally small skull
Small head circumference
Reduced head circumference
Decreased size of 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

Cause

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.

Diagnosis

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]

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

    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
    • Neonatologist
    • Radiologist

    Organizations

    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

      Learn more

      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.

            References

            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.

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