Also known as: Aspartoacylase deficiency; ASPA deficiency
Canavan disease (CD) is a severe neonatal disorder characterized by macrocephaly and lack of head control, with developmental delay in the first few months of life. Affected children become severely hypotonic, with failure to achieve developmental milestones such as sitting independently, or speech.
CD is a rare autosomal recessive disorder that usually presents in its severe neonatal form. There is a second mild / juvenile form of CD (much less common), characterised by mild developmental delay with often normal head circumference.
Clinical features of Canavan Disease (CD) may include:
- Hypotonia, macrocephaly and head lag in an infant after the age of 3-5 months.
- Developmental delays become increasingly obvious with increasing age.
- There is particular delay in motor skills; affected children are not able to sit, stand walk and talk.
- Optic atrophy is often present.
- Hearing is usually unaffected.
- Sleep disturbance, seizures and feeding difficulties may develop; with some children requiring assisted feeding.
- Children with the mild/juvenile form of CD may have normal or mildly delayed speech or motor development in early life.
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- CD is caused by mutations in the ASPA gene located on chromosome 17.
- It is one of a group of genetic disorders – leukodystrophies – which are characterized by degeneration of myelin in the phospholipid layer insulating the axon of the neuron. This results in vulnerable axons, unable to properly function.
- The ASPA gene synthesizes an enzyme called aspartoacyclase. Reduced aspartoacyclase activity prevents normal breakdown of N-acetyl aspartate and its accumulation interferes with the growth of the myelin sheath.
- 2 mutations account for 98% disease causing alleles in the Ashkenazi Jewish (AJ) population and 3% of disease causing alleles in non-AJ populations.
- Approximately 1:40 Ashkenazi Jews are carriers.
- The carrier rate in non-Jewish populations is unknown, however it is assumed to be much lower.
- Clinical diagnosis can be confirmed by genetic testing for mutations in the ASPA gene.
- 2 mutations account for 98% of disease causing alleles in the Ashkenazi Jewish population and 3% of alleles in non-Ashkenazi Jewish populations.
- A different mutation accounts for up to 60% of disease causing alleles in the non-Ashkenazi Jjewish population.
Treatment is symptomatic and supportive, and includes:
- Ensuring provision of adequate nutrition and hydration to affected individuals who are unable to feed independently. Gastrostomy may be needed to maintain adequate nutrition and hydration when swallowing difficulties develop.
- Protecting the airway.
- Physical therapy can maximize motor abilities and minimizes contractures.
In some cases, genetic counselling and testing may be appropriate for family members. Carrier testing and pre-natal testing is available for this condition.
- Life expectancy is variable. It is associated with high childhood mortality, however, it is common for patients with CD to survive into their teens and sometimes beyond.
- For children exhibiting features of Canavan Disease (CD), initial referral would usually be to a paediatrician. For Jewish patients, it is important to note the child’s ancestry and higher prevalence of CD in the Jewish population.
- For patients that have received a positive CD diagnosis:
- On-going management is usually under the care of a paediatrician with other specialist input as appropriate.
- Families may benefit from referral to a clinical genetics department to establish carrier status in other family members as appropriate.
There is currently no dedicated patient group for CD in the UK.
The Foundation is dedicated to preventing CD through education, testing and facilitating research efforts. The site provides information about the disease, activities of the Foundation, and a directory of international testing centres.
The NTSAD is dedicated to leading the fight to treat and cure Tay-Sachs, Canavan and related genetic diseases and to support affected families and individuals. It provides educational materials, information on the latest research, and many other resources for those affected.
European Leukodystrohpy Association (ELA)
ELA assists and supports families affected with a leukodystrophy, stimulates and funds research into leukodystrophies, and raises public awareness about these disorders.
This charity supports families with disabled children across the UK whatever their condition or disability. They provide information, advice and support and put families in touch with others affected by similar conditions so they can support each other.
Written by: Dr Jacky Megitt, Jnetics researcher.
Approved by: Dr Ming Lim MRCP PhD, Consultant Paediatric Neurologist, Evelina Children’s Hospital Children’s Neurosciences Centre, St. Thomas’ Hospital; Dr John Livingstone, Consultant Paediatric Neurologist, Leeds General Infirmary; and Dr Thomas Wassmer Lecturer in Cell Biology, School of Life and Health Sciences, Aston University.
Last review: 07.06.2018