A rare case of a long-lived patient with Canavan syndrome

Abstract

This case report describes the clinical case of a patient with Canavan Syndrome, a condition characterized by high mortality in infancy, who reached the age of 32. The article focuses on the patient's medical history, clinical and instrumental evaluations, and the treatment administered, then compares the patient's clinical history with that of other individuals affected by the same disease, and finally assesses the various treatment options and future therapeutic prospects for this condition. Canavan disease is a rare, progressive, autosomal recessive disorder that begins in infancy or early childhood [1,2]. It is caused by genetic mutation in the aspartoacylase (ASPA) gene, which encodes a metabolic enzyme synthesized by oligodendrocytes in the brain. ASPA mutations lead to a deficiency of the enzyme aspartoacylase resulting in accumulation of N-Acetylaspartic acid in the brain. This accumulation will result in oligodendrocyte dysfunction, axonal myelin degeneration and cerebral spongiform changes [3]. Sufficient data is unavailable to calculate the prevalence [4]. The neonatal form is the most common (85–90%) and is usually associated with the most severe symptoms while a less severe atypical Canavan disease (10%-15%) is associated with onset from infancy to adolescence, milder development delay, with or without regression. Typical features of the neonatal form include lethargy, listlessness, weak cry and suck, a lack of head control when the baby is pulled from a lying to a sitting position, hypotonia, poor visual tracking or blindness, vomiting, and seizures. Macrocephaly becomes prominent by the age of three to six months, and hypotonia eventually progresses to spasticity, hyperreflexia, extensor plantar responses, and tonic extensor spasms. It can also be present blindness due to optic atrophy. [5] No consensus clinical diagnostic criteria for Canavan disease have been established. Diagnosis is based on compatible clinical features and neuroimaging findings (spongiform degeneration and edema of the white matter, brain enlargement) associated with elevated levels of urine NAA and, on proton magnetic resonance spectroscopy (1/H-MRS), an increase in NAA, a reduction in Cr and choline, and an increase in lactate levels [6,7]. The molecular diagnosis of Canavan disease is established in a proband with biallelic pathogenic variant in the ASPA gene identified by molecular genetic testing [8]. There is no cure for Canavan disease. Supportive treatment is recommended, in particular to provide adequate hydration and nutrition, managing the risk of infections and protecting the airway [6]. Prognosis is variable, although most people with the neonatal/infantile form die in the first two decades of life. [5]