Meningoencephalitis in a novel mutation in MNGIE (mitochondrial neurogastrointestinal encephalomyopathy) ending a familial diagnostic odyssey: A case series report.

ABSTRACT

MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) is an ultra-rare autosomal recessive disorder that leads to mutations in the nuclear genes encoding thymidine phosphorylase. Symptoms include gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoplegia, sensorimotor neuropathy and asymptomatic leukoencephalopathy. We describe the first case of MNGIE with meningoencephalitis that ultimately led to a familial diagnosis ending a diagnostic odyssey. We retrospectively reviewed the electronic medical records and sent whole exome sequencing for the index case and his family members. We report the variant c.877T>C p.(Cys293Arg) found in TYMP gene in all affected siblings showed typical clinical manifestations related to MNGIE. To the best of our knowledge, this is not described in the literature nor in the population databases dbSNP (Single Nucleotide Polymorphism Database) and gnomAD (Genome Aggregation Database). Additionally, it is located in a highly conserved residue and the bioinformatic analysis suggests it is most probably deleterious. Moreover, we estimated 550 number of cases of MNGIE (including 5 cases in this study) after performing an extensive search in the literature across 3 databases from 1983-2023. In addition, we identified 44 patients with MNGIE-like phenotype in genes other than TYMP. MNGIE-like phenotype affects POLG1, RRM2B, LIG3, RRM1, MTTV1, and MT-RNR1 genes.

A rare neurological presentation unravels a family's medical mystery after years of no diagnosis MNGIE is a rare disease caused by changes in a gene that cause deficiency in an enzyme called thymidine phosphorylase. Patients complain of significant weight loss, tingling and numbness in their extremities, muscle weakness, digestive issues and drooping eyelids. We encountered a patient with symptoms and signs of inflammation of the brain and it's protective lining. However, laboratory tests were inconclusive whilst his condition kept deteriorating. A genetic analysis revealed a new mutation not described in the literature before. This has also helped to diagnose the entire family after years of not receiving an answer regarding their symptoms. We also found 550 cases of MNGIE published in the scientific literature from 1983 to 2023. This case highlights the importance of taking a family's entire family history and genetic testing to solve complex medical cases.