acute intermittent porphyria (aiP) is a rare inherited disorder, which is caused by the partial deficiency of hydroxymethylbilane synthase (HMBS), an enzyme of the heme biosynthetic pathway. abdominal pain, neuropsychiatric disturbance and neuropathy are the typical manifestations of the disease. complications such as posterior reversible encephalopathy syndrome (PreS), a rare type of brain lesion present on Mri, are also observed in patients with aiP. The present study reports on the case of a 36-year-old chinese female patient with aiP and PreS. Genomic dna were obtained from peripheral blood leukocytes and genomic regions of the HMBS gene were amplified as 2 fragments, which together contained all the exons and flanking intronic regions. Sanger sequencing of the amplified DNA fragments from the patient and the patient's family revealed a novel frameshift deletion (c.405-406delaa) in exon 8 of the HMBS gene. This mutation leads to a subsequent truncated protein (p.Glu135aspfsX74). The recombinant mutant protein had 62% activity relative to the wild-type protein but similar thermostability. It was confirmed that this novel mutation was the cause of aiP. accumulation of d-aminolevulinic acid (ala) due to HMBS dysfunction is a potential mechanism of PreS. The manifestation of PreS may be associated with ala-induced cytotoxicity and the destruction of the blood-brain barrier. in summary, in the present study, a novel pathogenic HMBS mutation was identified, expanding on the molecular heterogeneity of aiP.

ObjectiveThis study aimed to investigate the clinical spectra and outcomes in pregnancy-related optic neuritis (ON).MethodsWe analyzed the clinical subtype and prognosis of women with pregnancy-related ON in the neuro-ophthalmology department of the First Medical Center at the Chinese PLA General Hospital from January 2014 to December 2019.ResultsA total of 54 patients, including 21 (38.9%) with idiopathic ON (ION), 27 (50.0%) with aquaporin-4 (AQP4)-ON, and 6 (11.6%) with myelin oligodendrocyte glycoprotein (MOG)-ON, who experienced 58 informative pregnancies and 67 episodes of pregnancy-related ON were assessed. Among the ON attacks, there were 11 (16.4%) during pregnancy and 56 (83.6%) within 1 year postpartum (PP1) or after abortion, including 33 (49.3%) in the first trimester. In total, 14 (25.9%) patients with ON onset before pregnancy had a higher relapse rate during PP1 than within 1 year before pregnancy (p = 0.021), and 24 (85.7%) eyes with ION and nine (100%) with MOG-ON had significantly better visual outcomes (p ≥ 0.5) than those with AQP4-ON (14, 35%) (p < 0.001 and p < 0.001, respectively). Two AQP4-ON patients had premature birth and low baby weight, respectively. There were no birth defects or stillbirths.ConclusionThe significantly increased relapse rate and numerous cases of ON after pregnancy suggest that delivery adversely affects the course of ON.

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