Adult-Onset Hereditary Spastic Paraplegia 15 in a Saudi Patient with A Compound Heterozygous Variant in the ZFYVE26 Gene

Abstract

Hereditary spastic paraplegia (HSP) 15 is an autosomal recessive neurodegenerative disease caused by homozygous or heterozygous point mutations in the ZFYVE26 gene that encodes the spastizin protein, located on chromosome 14q22-q24. Hereditary spastic paraplegia has been rarely reported in Saudi Arabia. In this article, we reported a rare case of adult-onset HSP 15 with a pure form of the disease in a Saudi patient with a compound heterozygous variant in the ZFYVE26 gene. The present case suggests that a compound heterozygous mutation in the ZFYVE26 may be associated with a later-onset disease and a milder phenotype. Given the low prevalence of the disease as well as heterogenicity and variability of its presenting symptoms, HSP 15 may be difficult to diagnose. However, early diagnosis is important to prevent unnecessary extensive investigations, facilitate early symptomatic management and provide genetic counseling for family planning to those affected and their first and second-degree relatives.

FIGURE 1.

Family pedigree demonstrating the details of the proband’s family. The asterisk sign (*) represents the available sample for the study

FIGURE 2.

Patient’s images showing signs of renal osteodystrophy in both hands and feet

FIGURE 3.

MRI of the brain showing a subtle T2 hyperintensity in the internal capsule

FIGURE 4.

Spine X-ray showing Rugger Jersey spine

FIGURE 5.

Representative chromograph of ZFYVE26 Sanger sequencing read of the available family members. The proband II-1 is showing a heterozygous variant in the ZFYVE26 gene at position one c.5417G>A p.(Arg1806Lys) in exon 27 and a heterozygous variant in the ZFYVE26 gene exon 40 at position 2 c.7411A>G p.(Asn2471Asp), indicating a compound heterozygous mutation, whereas the II-2 a normal brother is showing wild type sequence at the same position