Canavan Disease

Excerpt

Clinical characteristics: Most individuals with Canavan disease have the neonatal/infantile form. Although such infants appear normal early in life, by age three to five months, hypotonia, head lag, macrocephaly, and developmental delays become apparent. With age, children with neonatal/infantile-onset Canavan disease often become irritable and experience sleep disturbance, seizures, and feeding difficulties. Swallowing deteriorates, and some children require nasogastric feeding or permanent feeding gastrostomies. Joint stiffness increases, so that these children resemble individuals with cerebral palsy. Children with mild/juvenile Canavan disease may have normal or mildly delayed speech or motor development early in life without regression. In spite of developmental delay most of these children can be educated in typical classroom settings and may benefit from speech therapy or tutoring as needed. Most children with mild forms of Canavan disease have normal head size, although macrocephaly, retinitis pigmentosa, and seizures have been reported in a few individuals.

Diagnosis/testing: The diagnosis of Canavan disease is established in a proband with typical clinical findings and elevated N-acetylaspartic acid (NAA) in urine and/or with biallelic pathogenic variants in ASPA identified by molecular genetic testing.

Management: Treatment of manifestations:

1. Neonatal/infantile Canavan disease. Treatment is supportive and directed to providing adequate nutrition and hydration, managing infectious diseases, and protecting the airway. Hospice care is a resource used by the families of the individuals affected by the disease. Physical therapy minimizes contractures and maximizes motor abilities and seating posture; special education programs enhance communication skills. Seizures are treated with anti-seizure medication. Gastrostomy may be needed to maintain adequate food intake and hydration when swallowing difficulties exist.

2. Mild/juvenile Canavan disease. May require speech therapy or tutoring but no special medical care.

Surveillance:

1. Neonatal/infantile Canavan disease. Follow up every six months to evaluate developmental status and evidence of any new problems.

2. Mild/juvenile Canavan disease. Annual routine follow up by a pediatric neurologist or a developmental pediatrician is indicated.

Genetic counseling: Canavan disease is inherited in an autosomal recessive manner. Each pregnancy of a couple in which both partners are heterozygous for a pathogenic variant in ASPA has a 25% chance of resulting in a child with Canavan disease, a 50% chance of resulting in a child who is an asymptomatic carrier, and a 25% chance of resulting in a child who is unaffected and not a carrier. Carrier testing is available on a population basis for individuals of Ashkenazi Jewish heritage. Carrier testing for at-risk relatives, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible when the pathogenic variants in the family are known.