Hereditary spastic paraplegia type 35 caused by a novel <i>FA2H</i> gene mutation

<p>  Hereditary spastic paraplegia (SPG) which were identified their locus has more than 60 subtypes ; however, the SPG35 type is quite rare. We encountered a SPG35 patient whose symptoms began at the age of 3 years and was diagnosed at the age of 19 years. The patient developed spastic paraplegia starting at 3 years and was referred to our hospital at 7 years. His brain MRI showed mild cerebellar and brainstem atrophy, but no abnormalities were found on blood biochemistry testing, urinalysis, blood gas analysis, EEG, somatosensory evoked potentials, and lower limb nerve conduction tests. Subsequently, in addition to the progression of spastic paralysis, the intellectual regression appeared. His brain MRI showed a high intensity signal in the white matter of the parietal occipital lobe on T2-weighted imaging. It was difficult to definitively diagnose hereditary spastic paraplegia, and at 19 years, he participated in an initiative on rare and undiagnosed diseases in pediatrics. A novel mutation (NM_024306.5 : c.137dup [p.Glu47Argfs^＊55]) was found in homozygous in the FA2H gene which encodes Fatty acid 2-hydroxylase by using trio-based whole-exome sequencing. The diagnosis was confirmed. In the analysis of the father, the mutation was found in heterozygous, and it was considered that there was uniparental disomy from the father. We reconsidered with radiologists and could point out the low signal bilaterally in the pallidum on T2-weighted imaging. In hereditary spastic paralysis, there are variations in the time and frequency of appearance of characteristic symptoms, so if there are multiple suggestive symptoms even without the appearance of specific symptoms, they should be listed as the highly probable differential diseases. In that case, definitive diagnosis including comprehensive gene analysis should be considered earlier.</p>