Urine N-Acetylaspartate Distinguishes Phenotypes in Canavan Disease DOI
Amanda Nagy, Florian Eichler, Annette Bley

et al.

Human Gene Therapy, Journal Year: 2024, Volume and Issue: 36(1-2), P. 45 - 56

Published: Dec. 4, 2024

Canavan disease (CD) is an ultra-rare autosomal recessive leukodystrophy caused by loss-of-function mutations in ASPA, which encodes aspartoacylase (ASPA), leading to accumulation of N-acetylaspartate (NAA). Patients with CD typically present profound psychomotor deficits within the first 6 months life and meet few motor milestones. Within a subset patients exhibits milder phenotype more milestone acquisition, possibly related greater residual ASPA activity. An ongoing natural history study literature search were leveraged compare urine NAA levels associated genotypes classified mild or typical CD, hypothesis that reflect activity therefore can distinguish between two phenotypes. Urine lower, on average (p < 0.0001), individuals (mean 525.3, range 25.2-1,335 mmol/mol creatinine [Cr]) compared 1,369, 391.7-2,420 Cr). Mutations R71H Y288C, variants may harbor activity, unique population (56%, 14/25) not found (0%, 0/39). In aggregate, phenotypes, suggesting ability

Language: Английский

Urine N-Acetylaspartate Distinguishes Phenotypes in Canavan Disease DOI
Amanda Nagy, Florian Eichler, Annette Bley

et al.

Human Gene Therapy, Journal Year: 2024, Volume and Issue: 36(1-2), P. 45 - 56

Published: Dec. 4, 2024

Canavan disease (CD) is an ultra-rare autosomal recessive leukodystrophy caused by loss-of-function mutations in ASPA, which encodes aspartoacylase (ASPA), leading to accumulation of N-acetylaspartate (NAA). Patients with CD typically present profound psychomotor deficits within the first 6 months life and meet few motor milestones. Within a subset patients exhibits milder phenotype more milestone acquisition, possibly related greater residual ASPA activity. An ongoing natural history study literature search were leveraged compare urine NAA levels associated genotypes classified mild or typical CD, hypothesis that reflect activity therefore can distinguish between two phenotypes. Urine lower, on average (p < 0.0001), individuals (mean 525.3, range 25.2-1,335 mmol/mol creatinine [Cr]) compared 1,369, 391.7-2,420 Cr). Mutations R71H Y288C, variants may harbor activity, unique population (56%, 14/25) not found (0%, 0/39). In aggregate, phenotypes, suggesting ability

Language: Английский

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