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Table 1 Summary of microscopic features in the gut of MNGIE cases

From: Gastrointestinal Dysmotility in MNGIE: from thymidine phosphorylase enzyme deficiency to altered interstitial cells of Cajal

Study Gender, age (years)/ total body weight (kg) Myogenic/ Neurogenic Histopathology Remarks
Bardosi A, et al. [23] Female, 42, 40 Fibrosis of SI submucosa and subserosa, hypertrophy of the tunica MM
Perez-Atayde AR, et al. [24, 25] -Female, 14, − -Male, 14, − Atrophy and fibrosis of the smooth muscle EL of MP, residual smooth muscle myocytes show cytoplasmic vacuoles, cytoplasmic eosinophilic inclusions (megamitochondria) observed by light microscopy in smooth muscle myocytes of MM and MP of the esophagus and SI and ganglion cells of the entire GI These studies suggest that noninvasive rectal biopsy can contribute to the diagnosis of MNGIE in additional to the standard diagnostic criteria [108]. Abnormal intestinal mitochondrial morphology/ genetics/ function as diagnostic markers for MNGIE.
Teitelbaum JE, et al. [29] -Female, 14, 23 Focal muscle absence, serosal granulomas, fibrosis, megamitochondria in SMCs of the MM (rectal suction biopsy), focal loss of Auerbach’s plexus, megamitochondria in ganglion cells of the MM (rectal suction biopsy)
Szigeti K, et al. [26] -Male, 17, − Atrophy of longitudinal EL of MP, hypertrophy of the inner circular smooth muscle bundles of the MP, swollen SMCs with pale cytoplasm, enlarged nerve cells, ganglion cells were infrequent
Blondon H, et al. [27] -Female, 26, 39 -Female, 30, 28 -Male, 22, 43 Atrophy and fibrosis of the EL of MP and vacuolated SMCs, hypertrophy of the inner layer of the MP, bundance of abnormally shaped megamitochondria with lipid droplets (EM) in MP smooth muscle myocytes (SI and gallbladder)
Giordano C, et al. [28, 30] 5 cases, summarized in reference [18] Chronic inflammation (mucosa), edema (submucosa), preserved inner layer of MP, atrophy and interstitial fibrosis limited to the smooth SMCs of the longitudinal EL of MP (stomach and more pronounced in SI), pyconic nuclei and cytoplasmic microvaculation in the smooth muscle cells of the EL (SI), vacuolated cytoplasm filled with swollen mitochondria and lipids (EM) - Low levels of mtDNA point mutations in myocytes, nerve fibers and ganglia of the myenteric plexus. - No mtDNA deletions in SI. - Mitochondrial proliferation and mtDNA depletion limited to the EL of the MP of the entire GI. - mtDNA depletion correlates with the atrophy and interstitial fibrosis - Baseline mtDNA levels are low in MP smooth muscles of SI of a normal subject, predisposing the SI smooth muscles to nucleoside imbalances and selective SI myopathy in MNGIE patients.
Zimmer V, et al. [31] - Female, 35, 31 Absence of the normally abundant c-Kit-positive ICC around the myenteric plexus, in intermuscular septa and within muscular plexus - Absence of ICC can be an early event of GI dysmotility preceding myo/neurogenic morphological changes. - Absence of ICC can be due to cell death, transdifferentiation into smooth muscle phenotype or their loss can be a secondary event due to mitochondrial energy failure. - Dysfunctional ICC networks account for disturbed pacemaker activity and interfere with neurotransmission.
Yadak R, et al. [71] 3 cases summarized in reference [61] Fibrosis and atrophy of the external layer of the tunica muscularis propria, ICCs were completely lost in all MNGIE patients Intestinal muscle wall atrophy and complete loss of Cajal cells in treated patients were not recovered after HSCT.
  1. EL external layer, EM electron microscopy, GI gastrointestinal, HSCT hematopoietic stem cell transplantation, ICC interstitial cells of Cajal, MM muscularis mucosae, MP muscularis propria, SI small intestine, SMCs small muscle cells