Tremor as an early sign of hereditary spastic paraplegia due to mutations in ALDH18A1

BackgroundThe ALDH18A1 gene is located at 10q24.1 and encodes delta-1-pyrroline-5-carboxylate synthetase (P5CS), a mitochondrial bifunctional enzyme that catalyzes the first two steps in de novo biosynthesis of proline, ornithine, citrulline, arginine. ALDH18A1-related disorders have been classified into four groups, such as autosomal dominant recessive hereditary spastic paraplegia (SPG9A SPG9B, respectively), well cutis laxa (ADCL3 ARCL3A, respectively). Neurodegeneration characteristic feature all groups.Case reportHere, we report girl with compound heterozygous disease-causing variants (c.-28-2A>G c.383G>A, p.Arg128His) gene, revealed by whole exome sequencing. The c.-28-2A>G variant intron 1, inherited from mother, novel mutation, while c.383G>A exon 4, father, has already reported. patient presented vigorous infantile tremor preceding progressive paraplegia. Dysmorphic features included elongated face, deep-set ears, upturned nose, long philtrum pointed chin. Intrauterine postnatal growth retardation, microcephaly, global developmental delay profound intellectual disability were also noticed. Blood fasting ammonia level, plasma ornithine arginine levels normal, citrulline level was slightly decreased. Brain MRI moderate hypoplasia corpus callosum reduction white matter volume.ConclusionsThe represents rare form paraplegias. early onset tremor, lower limb spasticity appears to be unique manifestation neurodegeneration this case.