Case Report: Novel Arylsulfatase A (ARSA) Gene Mutations in a Patient With Adult-Onset Metachromatic Leukodystrophy Misdiagnosed as Multiple Sclerosis.

Lulu Xu,Meixiang Zhong,Wenjing Yan,Yajuan Wang,Zhihong Wang,Jing Zhao,Hongyun Yu,Xueping Zheng,Jie Song,Zhencui Yang

doi:10.3389/fneur.2020.576881

Abstract

Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary disorder characterized by the accumulation of sulfatide in the central and peripheral nervous systems. Herein, we present the case of an adult patient with MLD who had mild cognitive and psychiatric dysfunctions and severe vision disturbance, who was initially misdiagnosed as multiple sclerosis. Through genetic screening, this patient was later identified to have a full deletion of exon 4 and the novel p.P220L mutation in the arylsulfatase A (ARSA) gene. These mutations are reported for the first time in MLD. These data will help to update the mutation profiles of patients with MLD.

Highlights

Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary disorder characterized by the accumulation of sulfatide in the white matter of the central nervous system (CNS) and peripheral nervous system (PNS) as well as in other non-neural tissues [1]
It is caused by a deficiency of the sulfatide-degrading lysosomal enzyme arylsulfatase A (ARSA), which leads to progressive demyelination that causes a variety of neurological symptoms [2]
Before the examination of brain Magnetic resonance imaging (MRI), ARSA activity, sulfatides, or molecular diagnosis, patients are often misdiagnosed with schizophrenia, affective disorders, or personality disorders [6]

Summary

INTRODUCTION

Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary disorder characterized by the accumulation of sulfatide in the white matter of the central nervous system (CNS) and peripheral nervous system (PNS) as well as in other non-neural tissues [1]. Low ARSA activities have been reported in healthy individuals who are carriers of a pseudodeficiency allele but without clinical signs of MLD [10]. The pain was recurrent, lasting ∼2 h per episode, which was further aggravated by eye activity or fatigue and relieved after rest Her binocular vision decreased from 1.5 to 0.15 in the right eye and was 0.3 in the left eye; her visual field, color perception, and ocular fundus examination findings were normal at presentation. After carefully reviewing her medical history, we found that she had been diagnosed with depression due to hypothymia and slow movement in another hospital, before visiting our hospital. Mutation (Figure 4), and a known mutation, p.T393S, in the ARSA gene

DISCUSSION

Findings

ETHICS STATEMENT