RT Journal Article SR Electronic T1 Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48) JF Neurology Genetics JO Neurol Genet FD Lippincott Williams & Wilkins SP e98 DO 10.1212/NXG.0000000000000098 VO 2 IS 5 A1 Hirst, Jennifer A1 Madeo, Marianna A1 Smets, Katrien A1 Edgar, James R. A1 Schols, Ludger A1 Li, Jun A1 Yarrow, Anna A1 Deconinck, Tine A1 Baets, Jonathan A1 Van Aken, Elisabeth A1 De Bleecker, Jan A1 Datiles, Manuel B. A1 Roda, Ricardo H. A1 Liepert, Joachim A1 Züchner, Stephan A1 Mariotti, Caterina A1 De Jonghe, Peter A1 Blackstone, Craig A1 Kruer, Michael C. YR 2016 UL http://ng.neurology.org/content/2/5/e98.abstract AB Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious.Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1.Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material.Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders.HSP=hereditary spastic paraplegia; NCS=nerve conduction study; PAS=periodic acid-Schiff; PSP=progressive supranuclear palsy; SCA=spinocerebellar ataxia