A family study of Zellweger spectrum disorders due to mutations in the PEX10 gene and literature review
10.3760/cma.j.cn113694-20230112-00024
- VernacularTitle:PEX10基因突变导致Zellweger谱系疾病一家系研究并文献复习
- Author:
Xinyu CUI
1
;
Li DAI
;
Tongxia ZHANG
;
Jingli SHAN
;
Guangrun XU
;
Yuying ZHAO
Author Information
1. 山东大学齐鲁医院神经内科，济南250012
- Keywords:
Peroxisomes;
Zellweger spectrum disorders;
Ataxia;
Peripheral neuropathy
- From:
Chinese Journal of Neurology
2023;56(10):1150-1157
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To report a family of Zellweger spectrum disorders (ZSD) caused by mutations in the PEX10 gene and to increase the level of awareness of the disease among clinicians. Methods:The clinical and genetic data of a brother-sister co-morbidity family with ZSD due to PEX10 gene mutation admitted to the Department of Neurology, Qilu Hospital of Shandong University in July 2022 were collected and a literature review was performed. Results:The proband was a 24-year-old female who was admitted to the Qilu Hospital of Shandong University due to unstable walking for 8 years and aggravated for 1 year with squatting effort. Cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography suggested peripheral neuropathy with motor and sensory involvement, and pure tone hearing threshold measurement showed neurogenic deafness. The 15-year-old brother of the proband presented with "unsteadiness in walking and difficulty in squatting for 2 years". His cranial MRI and electromyography were similar to those of the proband, and his laboratory results suggested abnormal liver function. The whole exon sequencing results of the proband suggested a compound heterozygous mutation in the PEX10 gene with c. 992G>A(p. R331Q) and c. 988T>C(p. C330R) mutations and both were likely pathogenic mutations and respectively from her parents. And her brother also carried the above variants. A total of 9 case reports in English literature (1 of which was published by domestic scholars) were retrieved from major domestic and international databases on PEX10 gene mutations causing ZSD, with a total of 15 patients, most of whom had childhood and adolescent onset. The most common initial symptom was slowly progressed ataxia. The majority of patients showed cerebellar atrophy on cranial MRI and peripheral neuropathy was found in the most patients.The 2 patients were suggested to have phytic acid-free food, at the same time, they bagan taking L-arginine and ursodeoxycholic acid. Fortunately,both the ataxia symptom and liver function of them were dramatically alleviated 3 months later. Conclusions:For the patients with unexplained ataxia with polyneuropathy and abnormal liver function,the possibility of ZSD should be considered. Phytic acid-free food, L-arginine and ursodeoxycholic acid supplement may be beneficial for the ZSD patients.
