Possible adult-onset hypophosphatasia variant presenting as young-onset parkinsonism with limited levodopa responsiveness

Résumé fourni par la source

A woman in her late 40s presented with a 1 year history of progressive symmetrical rest tremor, bradykinesia, rigidity, hypophonia and postural instability (Movement Disorder Society-sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III 41) without musculoskeletal symptoms or family history. Routine investigations were unremarkable except low-normal serum alkaline phosphatase (41 U/L, range 35-104), mild anaemia and vitamin D insufficiency; brain MRI showed blooming in bilateral globus pallidi. Minimal to no improvement observed at 1 month on modest dopaminergic dosing (MDS-UPDRS III 38). Whole-exome sequencing identified a heterozygous pathogenic frameshift variant c.388del (p.Val130Cysfs*1) in ALPL (alkaline phosphatase, liver/bone/kidney) gene. In the absence of classical skeletal features and without substrate testing, this finding is suggestive of a possible mild adult hypophosphatasia phenotype. This case highlights a potential association between ALPL variants and parkinsonism and underscores the role of genetic testing in atypical presentations.

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