Aldh18a1 gene

ALDH18A1 is the acronym for "Aldehyde dehydrogenase 18 family member A1" a gene coding for an aldehyde dehydrogenase located in the mitochondria and involved in the synthesis of proline, arginine and ornithine (gene locus: 10q24.1). This gene codes for a carboxylate synthetase located in the mitochondria. This delta-1-pyrroline-5-carboxylate synthetase catalyses the first two steps of the de novo biosynthesis of proline, ornithine and arginine. The enzyme is bifunctional and converts glutamate in 2 steps into delta-1-pyrroline-5-carboxylate, which is catalysed successively by the domains L-glutamate-5-kinase (G5K) and L-glutamyl-5-phosphate reductase (G5PR) (Panza et al. 2016).

Numerous mutations have been detected for this gene, which result in different disease patterns:

• Pathogenic germline mutation(s): Cutis laxa, autosomal dominant
• Pathogenic germline mutation(s): DeBarsy syndrome A, ALDH18A1-dependent
• Pathogenic germline mutation(s): (loss of function) Spastic paraplegia, autosomal dominant, type 9A
• Pathogenic germline mutation(s):(loss of function) Spastic paraplegia, autosomal dominant, type 9B
• Pathogenic germline mutation(s): (loss of function) Spastic paraplegia, autosomal recessive, type 9B