CYP2U1: An emerging treatable neurometabolic disease with cerebral folate deficiency in 2 Chinese brothers

Abstract

With the rapid advancement of medical technologies in genomic and molecular medicine, the number of treatable neurometabolic diseases is quickly expanding. Spastic paraplegia 56 (SPG56), one of the severe autosomal recessive forms of neurodegenerative disorders caused by pathogenic variants in the CYP2U1 gene, has no reported specific targeted treatment yet. Here we report 2 Chinese brothers with CYP2U1 bi-allelic pathogenic variants with cerebral folate deficiency who were treated for over a decade with folinic acid supplement. Patients have remained stable under therapy.

Keywords: 5-MTHF; 5-methyltetrahydrofolate; CYP2U1; Cerebral folate; Cerebral folate deficiency; Folinic acid; Spastic paraplegia 56.

Fig. 1

Non-contrast CT in 2015 (aged 13) demonstrated in left globus pallidus and frontal subcortical white matter calcifications (arrows).

Fig. 2

A: MRI using susceptibility weight sequence showed blooming artefacts in globus pallidus and subcortical white matter of the bilateral frontal and left parietal lobes (arrows), suggesting presence of mineral deposits. B: Non-contrast CT in 2018 demonstrated bilateral frontal and parietal subcortical white matter hyperdensities in keeping with calcifications (arrowheads).