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Atypical MRI findings in Canavan disease: a patient with a mild course
C Yalcinkaya1, G Benbir, G S Salomons
1Division of Child Neurology, Department of Neurology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey. cyalcin@ideefixe.com
Abstract:
Canavan disease is a severe, progressive leukodystrophy with an autosomal recessive inheritance, caused by aspartoacylase (ASPA) deficiency. The characteristic MRI features include diffuse, symmetrical white matter degeneration in the subcortical areas, with bilateral involvement of the globus pallidus. Proton magnetic resonance spectroscopy of the brain shows an increase in the concentration of N-acetylaspartic acid (NAA). The altered NAA metabolism has been traced to mutations in the gene encoding ASPA, located on chromosome 17 (17p13-ter). We present here a patient with a mild form of Canavan disease confirmed with the absent ASPA activity, atypical MRI findings, related to compound heterozygosity for a missense mutation, p.Tyr288Cys, and the known pan-European mutation, the p.Ala305Glu.
Insights
Canavan disease, a rare genetic disorder, results from aspartoacylase (ASPA) deficiency. This study details a mild case with unique genetic mutations and atypical MRI findings, advancing understanding of leukodystrophy.
Area of Science:
- Neurogenetics
- Biochemistry
- Medical imaging
Background:
- Canavan disease is a severe, progressive leukodystrophy inherited in an autosomal recessive pattern.
- It is caused by a deficiency in the enzyme aspartoacylase (ASPA).
- Characteristic findings include white matter degeneration on MRI and elevated N-acetylaspartic acid (NAA) in the brain.
Observation:
- A patient presented with a mild form of Canavan disease.
- The patient exhibited atypical magnetic resonance imaging (MRI) findings.
- Genetic analysis revealed compound heterozygosity for two ASPA gene mutations: p.Tyr288Cys and p.Ala305Glu.
Findings:
- The patient had absent ASPA activity, confirming the diagnosis.
- The specific combination of mutations resulted in a milder phenotype than typically observed.
- The missense mutation p.Tyr288Cys, in conjunction with the pan-European p.Ala305Glu mutation, contributed to the atypical presentation.
Implications:
- This case expands the spectrum of Canavan disease phenotypes and genotype-phenotype correlations.
- Understanding these specific mutations aids in diagnosing and potentially managing milder forms of the disease.
- Further research into ASPA mutations can inform genetic counseling and therapeutic strategies for leukodystrophies.
