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Mild elevation of N-acetylaspartic acid and macrocephaly: diagnostic problem
Sankar Surendran1, Fiona J Bamforth, Alicia Chan
1Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555-0359, USA.
Journal of Child Neurology
|December 31, 2003
Summary
This study details a patient with mild Canavan disease symptoms, including macrocephaly and elevated N-acetylaspartic acid. Genetic analysis revealed novel mutations explaining the atypical presentation and enzyme defect.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- Canavan disease diagnosis typically involves elevated N-acetylaspartic acid (NAA) in urine and specific clinical/imaging findings.
- Atypical presentations of Canavan disease pose diagnostic challenges.
Observation:
- A 13-year-old male presented with macrocephaly, mild developmental delay, bilateral basal ganglia lesions, cortical blindness, and retinitis pigmentosa.
- Urine N-acetylaspartic acid levels were slightly elevated (99.90 +/- 4.00 microg/mg creatinine), bordering the normal range (< 83 microg/mg creatinine).
- Aspartoacylase activity was absent in cultured skin fibroblasts.
Findings:
- Genomic analysis identified an intronic mutation disrupting exon 3 splicing and a missense mutation (Y288C) in exon 6 of the aspartoacylase gene.
- Expression studies indicated the exon 6 mutation (Y288C) did not impair aspartoacylase activity.
- The combined mutations likely contribute to the patient's unique biochemical and clinical phenotype.
Implications:
- This case expands the understanding of genotype-phenotype correlations in Canavan disease.
- Identified mutations provide insights into aspartoacylase enzyme function and splicing defects.
- Highlights the importance of genetic analysis in diagnosing atypical neurological disorders.