Mast Syndrome Outside the Amish Community: SPG21 in Europe.

Matthias Amprosi,Sylvia Boesch,Constanze Gallenmüller,Claudia Stendel,Wolfgang Nachbauer,Anna Hussl,Elisabetta Indelicato,Andreas Eigentler,Thomas Klopstock

doi:10.3389/fneur.2021.799953

Abstract

Background:Mast syndrome is a rare disorder belonging to the group of hereditary spastic paraplegias (HSPs). It is caused by bi-allelic mutations in the ACP33 gene, and is originally described in Old Order Amish. Outside this population, only one Japanese and one Italian family have been reported. Herein, we describe five subjects from the first three SPG21 families of German and Austrian descent.Methods:Five subjects with complicated HSP were referred to our centers. The workup consisted of neurological examination, neurophysiological and neuropsychological assessments, MRI, and genetic testing.Results:Onset varied from child- to adulthood. All patients exhibited predominant spastic para- or tetraparesis with positive pyramidal signs, pronounced cognitive impairment, ataxia, and extrapyramidal signs. Neurophysiological workup showed abnormal motor and sensory evoked potentials in all the patients. Sensorimotor axonal neuropathy was present in one patient. Imaging exhibited thin corpus callosum and global brain atrophy. Genetic testing revealed one heterozygous compound and two homozygous mutations in the ACP33 gene.Conclusion:Herein, we report the first three Austrian and two German patients with SPG21, presenting a detailed description of their clinical phenotype and disease course. Our report adds to the knowledge of this extremely rare disorder, and highlights that SPG21 must also be considered in the differential diagnosis of complicated HSP outside the Amish community.

Highlights

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of genetic disorders sharing a core phenotype of progressive spastic paraparesis
SPG21 in Europe latter group belongs the Mast syndrome (SPG21), a complicated HSP accompanied by dementia, extrapyramidal and cerebellar signs
Mast syndrome is caused by bi-allelic mutations in the ACP33 (SPG21; HSP-ACP33) gene, coding for a protein called maspardin (5)

Summary

Introduction

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of genetic disorders sharing a core phenotype of progressive spastic paraparesis. They are divided into pure and complicated forms, the latter being characterized by additional symptoms such as ataxia, extrapyramidal symptoms, cognitive impairment, seizures, and peripheral nervous system involvement (1, 2). Mast syndrome is a rare disorder belonging to the group of hereditary spastic paraplegias (HSPs) It is caused by bi-allelic mutations in the ACP33 gene, and is originally described in Old Order Amish. Outside this population, only one Japanese and one Italian family have been reported. We describe five subjects from the first three SPG21 families of German and Austrian descent

Methods

Results

Conclusion