Ornithine transcarbamylase deficiency combined with type 1 diabetes mellitus - a challenge in clinical and dietary management

Abstract

Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle defect. The clinical presentation in female manifesting carriers varies both in onset and severity. We report on a female with insulin dependent diabetes mellitus and recurrent episodes of hyperammonemia. Since OTC activity measured in a liver biopsy sample was within normal limits, OTC deficiency was initially excluded from the differential diagnoses of hyperammonemia. Due to moderately elevated homocitrulline excretion, hyperornithinemia-hyperammonemia-homocitrullinuria-syndrome was suggested, but further assays in fibroblasts showed normal ornithine utilization. Later, when mutation analysis of the OTC gene became available, a known pathogenic missense mutation (c.533C>T) in exon 5 leading to an exchange of threonine-178 by methionine (p.Thr178Met) was detected. Skewed X-inactivation was demonstrated in leukocyte DNA. In the further clinical course the girl developed marked obesity. By initiating physical activities twice a week, therapeutic control of both diabetes and OTC deficiency improved, but obesity persisted. In conclusion, our case confirms that normal hepatic OTC enzyme activity measured in a single liver biopsy sample does not exclude a clinical relevant mosaic of OTC deficiency because of skewed X-inactivation. Mutation analysis of the OTC gene in whole blood may be a simple way to establish the diagnosis of OTC deficiency. The joint occurrence of OTC deficiency and diabetes in a patient has not been reported before.

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

“…These anemia responsible genes might be candidate biomarkers or therapeutic targets for CD. CXCR1 [679], CXCL1 [680], C2 [681], MMP3 [682], TAP1 [683], NOS2 [684], CXCL10 [685], SLC11A1 [686], GDF15 [687], IL1RN [688], PYGL (glycogen phosphorylase L) [689], CYP27B1 [690], SOCS3 [691], CD55 [692], CXCR2 [693], CCL3 [694], CCL2 [695], SOD2 [696], CD14 [697], IGFBP2 [698], PCSK9 [699], [700], IDO1 [701], FOXP3 [702], CD163 [703], LPL (lipoprotein lipase) [704], TLR2 [705], CCR2 [706], VWF (von Willebrand factor) [707], NOD2 [708], ATF3 [709], TIMP1 [682], ICAM1 [710], FFAR2 [711], IFNG (interferon gamma) [712], APOE (apolipoprotein E) [713], IL6 [714], CCL4 [715], CA2[716], MMP12 [717], MMP2 [718], CCL1 [719], CD24 [720], PLAU (plasminogen activator, urokinase) [721], CTLA4 [722], MASP1 [723], MPO (myeloperoxidase) [724], HP (haptoglobin) [725], MMP10 [726], CD300E [727], CUBN (cubilin) [728], SLC19A3 [729], APOB (apolipoprotein B) [730], APOC3 [731], HMGCS2 [732], OTC (ornithine transcarbamylase) [733], ACE2 [734], SLC22A4 [735], SLC22A5 [735], DPP4 [736], ACE (angiotensin I converting enzyme) [737], SLC6A19 [738], BTNL2 [739], FCRL3 [451], BCHE (butyrylcholinesterase) [740] and APOM (apolipoprotein M) [741] might be involved in type 1 diabetes mellitus. These type 1 diabetes mellitus responsible genes might be important participant in CD.…”

Transcriptome Signatures Reveal Candidate Key Genes in the Peripheral Blood Mononuclear Cells of Patients With Coronary Artery Disease

“…Enriched genes such as CCR2 [56], CCL19 [57], CX3CL1 [58], CXCL12 [59], IL20 [60], epidermal growth factor receptor (EGFR) [61], ERBB3 [62], adrenomedullin (ADM) [63], SCUBE1 [64], LMAN1L [65] and EGFL7 [66] were responsible for pathogenesis of CAD. Enriched genes such as CXCL6 [67], BMP7 [68], RXFP2 [69], BRS3 [70], FFAR3 [71], neuropeptide B (NPB) [72], SPON2 [73], FCN3 [74], REG3A [75] and ornithine carbamoyltransferase (OTC) [76] were culpable for pathogenesis of diabetes, but these genes may be involved in development of CAD. Enriched genes such as COL18A1 [77], cortistatin (CORT) [78], guanine nucleotide binding protein (G protein) [79] and MUC2 [80] were involved in development of obesity, but these genes may be associated with pathogenesis of CAD.…”

Transcriptome signatures reveal candidate key genes in the peripheral blood mononuclear cells of patients with coronary artery disease and prediction of small drug molecules

“…Genes such as CCR2 [61], CCL19 [62], CX3CL1 [63], CXCL12 [64], IL20 [65], epidermal growth factor receptor (EGFR) [66], ERBB3 [67], adrenomedullin (ADM) [68], SCUBE1 [69], LMAN1L [70] and EGFL7 [71] were responsible for pathogenesis of CAD. Genes such as CXCL6 [72], BMP7 [73], RXFP2 [74], BRS3 [75], FFAR3 [76], neuropeptide B (NPB) [77], SPON2 [78], FCN3 [79], REG3A [80] and ornithine carbamoyltransferase (OTC) [81] were culpable for pathogenesis of diabetes, but these genes might be involved in development of CAD. Genes such as COL18A1 [82], cortistatin (CORT) [83], guanine nucleotide binding protein (G protein) [84] and MUC2 [85] were involved in development of obesity, but these genes might be associated with pathogenesis of CAD.…”