Neuropediatrics
DOI: 10.1055/s-0044-1788729

Francesca M. A. Papoff

1   Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy

2   Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

,

Guja Astrea

1   Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy

,

Serena Mero

3   Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Pisa, Italy

,

Laura Chicca

1   Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy

2   Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

,

Sara Satolli

3   Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Pisa, Italy

,

Rosa Pasquariello

1   Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy

,

1   Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Pisa, Italy

2   Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

,

Alessandra Tessa

3   Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Pisa, Italy

,

Filippo M. Santorelli

3   Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Pisa, Italy

› Author Affiliations Funding This research was supported in part by 2023 RC 5 × 1000, RF-2019–12370112 (to A.T.), and Ministero della Salute Grant SG-2021–12375552 (to S.M.).
› Further Information Also available at    Buy Article Permissions and Reprints Abstract

Hereditary spastic paraplegias (HSPs) are a genetically heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower limb spasticity with pyramidal weakness. Around a dozen potential molecular mechanisms are recognized. Childhood HSP is a significant diagnostic challenge in clinical practice. Mutations in AP5Z1, which are associated with spastic paraplegia type 48 (SPG48), are extremely rare and seldom described in children.

We report the clinical, radiologic, and molecular studies performed in a child harboring novel biallelic mutations in AP5Z1.

The child presented a neurodevelopmental disorder with slight lower limb pyramidal signs. Brain magnetic resonance imaging (MRI) showed minimal white matter changes in the frontal horns of the lateral ventricles and a normally shaped corpus callosum. Western blotting in cultured skin fibroblasts indicated reduced protein expression, which confirmed the genetic diagnosis and framed this as a case of protein reduction in a context of impaired autophagy.

Our findings expand the spectrum of phenotypes associated with mutations in AP5Z1, highlighting their clinical and pathophysiologic overlap with lysosomal storage disorders. SPG48 should be considered in the differential diagnosis of neurodevelopmental disorders even when pyramidal signs are minimal and brain MRI not fully informative.

Keywords HSP - AP5Z1 - SPG48 - neurodevelopmental disorders - lysosomal storage disorders Publication History

Received: 23 April 2024

Accepted: 10 July 2024

Article published online:
26 July 2024

© 2024. Thieme. All rights reserved.

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