A very early onset MNGIE-like syndrome with POLG1 mutation and accompanying leukoencephalopathy.

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a well-known mitochondrial depletion syndrome. Since Van Goethem et al. described MNGIE syndrome with pathogenic POLG1 mutations in 2003, POLG1 gene became a target for MNGIE patients. Cases with POLG1 mutations strikingly differ from classic MNGIE patients due to a lack of leukoencephalopathy. Here we present a female patient with very early onset disease and leukoencephalopathy compatible with classic MNGIE disease who turned out to have homozygous POLG1 mutation compatible with MNGIE-like syndrome, mitochondrial depletion syndrome type 4b.

A novel thymidine phosphorylase mutation in a family with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Molecular docking, dynamic simulation and computational investigations.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE; OMIM 603041) is a rare inherited metabolic disorder mostly caused by mutations in TYMP gene encoding thymidine phosphorylase (TP) protein that affects the mitochondrial nucleotide metabolism. TP, functionally active as a homodimer, is involved in the salvage pathway of pyrimidine nucleosides. MNGIE-like syndrome having an overlapping phenotype of MNGIE was also described and has been associated with mutations in POLG and RRM2B genes. In the present study, we report the molecular investigation of a consanguineous family including two patients with clinical features suggestive of MNGIE syndrome. Bioinformatics analyses were carried out in addition to mtDNA deletion screening and copy number quantification in the blood of the two patients. Whole exome sequencing and Sanger sequencing analyses revealed the segregation in the affected family a novel mutation c.1205T>A (p.L402Q) within the exon 9 of the TYMP gene. In addition, mtDNA analysis revealed the absence of mtDNA deletions and a decrease of the copy number in the blood of the two patients of the studied family. The p.Leu402Gln mutation was located in a conserved amino acid within the α/ß domain of the TP protein and several software supported its pathogenicity. In addition, and based on docking and molecular dynamic simulation analyses, results revealed that L402Q caused a conformational change in TP mutated structure and could therefore alter its flexibility and stability. These changes prevent also the formation of stable homodimer leading to non-functional protein with partial or complete loss of its catalytic activity.

Endocarditis in Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) Syndrome: The First in the Literature.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndromes is a rarely seen multisystem disorder with autosomal recessive inheritance due to thymidine phosphorylase gene mutation. It is characterized by progressive external ophthalmoplegia and/or pitosis, progressive gastrointestinal dismotility and abdominal pain, postprandial emesis, cachexia, demyelinating peripheral neuropathy, symmetrical and distal weakness especially in lower extremities and diffuse leucoencephalopathy in cranial magnetic resonance. Endocarditis is the infectious and inflammatory disease of the endothelial surface of the heart. MNGIE syndrome is a condition in which immune system is suppressed and infection risk increased. Herein we summarized a previously not reported endocarditis case in a patient with MNGIE syndrome who was under follow up for three years. In MNGIE syndrome of acute dyspnea, infective endocarditis should be kept in mind and prompt evaluation for surgical treatment should be done.