Autosomal dominant SPG9: intrafamilial variability and onset during pregnancy

Area of Science:

• Genetics
• Neurology

Background:

• The ALDH18A1 gene encodes delta-1-pyrroline-5-carboxylate synthase (P5CS).
• Mutations in ALDH18A1 cause autosomal recessive developmental delay and autosomal dominant spastic paraplegia type 9 (AD SPG9).

Observation:

• A three-generation family with AD SPG9 was investigated.
• Low fasting plasma citrulline levels, detected via amino acid chromatography (AAC), were an initial indicator.
• Spastic paraplegia symptoms aggravated during pregnancy in two patients.
• Disease presentation varied from severe childhood-onset to mild late-onset forms.

Findings:

• This study highlights the ALDH18A1 gene's role in AD SPG9.
• Pregnancy can transiently or permanently worsen spastic paraplegia in SPG9 patients.
• Plasma citrulline levels serve as a valuable biomarker for AD SPG9.
• The disease exhibits variable clinical expression.

Implications:

• The findings suggest a link between neurological symptoms and amino acid metabolism, particularly during pregnancy.
• Amino acid supplementation may benefit SPG9 patients.
• Early detection of AD SPG9 is possible through plasma citrulline testing.