Microvillus inclusion disease, a diagnosis to consider when abnormal stools and neurological impairments run together due to a rare syntaxin 3 gene mutation.

BACKGROUND: Microvillus Inclusion Disease (MVID) was first described in the literature in 1978 with presentation of severe watery diarrhea, failure to thrive, and metabolic acidosis. Mutations in the myosin Vb (MYO5B) gene have been identified as causative for MVID, but other clinical manifestations and associations with novel mutations are lacking. METHODS: We report a full-term infant admitted to the neonatal intensive care unit (NICU) with abdominal distension and inability to sustain full enteral feeds. A retrospective chart review and review of the literature was performed. RESULTS: An infant with abnormal, mucoid-like stringy stools was incidentally found to have severe metabolic acidosis on routine lab monitoring. Acidosis corrected with total parenteral nutrition (TPN), but the infant experienced recurrent episodes of acidosis with enteral feeds. He was also noted to have abnormal ocular movements, fluctuating tonicity, and staring spells. He underwent an extensive workup and the diagnosis of microvillus inclusion disease was made by findings on electron microscopy. The diagnosis was confirmed with whole exome sequencing, showing a rare homozygous mutation in the syntaxin 3 (STX3) gene. This is the fifth reported patient with microvillus inclusion disease with a mutation in this gene, and the first with abnormal neurologic findings. CONCLUSION: It is important to consider MVID in the differential diagnosis of a neonate or infant with abnormal stools, metabolic acidosis, with and without neurologic symptoms for prompt referral and treatment.

Alterations of the enteric smooth musculature in diverticular disease.

BACKGROUND: The pathogenesis of diverticular disease (DD) is considered to be multifactorial and involves intestinal motor disturbances and an underlying enteric neuromuscular pathology. While an enteric neuropathy has been well documented, actual studies on concomitant alterations of the enteric musculature are limited. This study is aimed at reassessing the smooth muscle tissue by histological, ultrastructural and molecular-biological approaches. METHODS: Full-thickness sigmoid specimens were obtained from patients with DD (n = 20) and controls (n = 19). Morphometric analysis was performed to evaluate the thickness and connective tissue index of the circular and longitudinal muscle layers as well as the myenteric plexus. Structural alterations were determined by light and transmission electron microscopy. mRNA profiles of components of the contractile smooth muscle apparatus including smooth muscle α-actin, smoothelin, histone deacetylase 8, and smooth muscle myosin heavy chain (SMMHC) were assessed by qPCR. Altered gene expression levels were confirmed at protein level by immunohistochemistry. RESULTS: Compared to controls, patients with DD showed (1) increased thickness of the circular and longitudinal muscle layers, (2) architectural alterations of smooth muscle cells, (3) increased connective tissue index of the longitudinal muscle layer, (4) focally reduced density of myofilaments at ultrastructural level, (5) specific down-regulation of SMMHC mRNA levels, (6) decreased immunoreactivity of SMMHC, (7) oligo-neuronal hypoganglionosis. CONCLUSIONS: DD is associated with distinct structural and functional alterations of the enteric musculature. The enteric myopathy is characterized by disturbed muscular architecture, connective tissue replacement and loss of specific myofilaments and thus may contribute to the pathogenesis and progression of DD.

Colonic diverticulitis in adolescents: an index case and associated syndromes.

Diverticular disease of the colon, a common problem among adults, is diagnosed rarely in children. We report an adolescent patient with sigmoid diverticulitis who required operative treatment. Pediatric patients with the complications of diverticula typically have conditions that result in genetic alterations affecting the components of the colonic wall. Our patient had Williams-Beuren syndrome, although Ehlers-Danlos syndrome, Marfan syndrome, and cystic fibrosis may also be associated with colonic diverticula in adolescence. Pediatric patients with these disorders who experience abdominal pain should be evaluated for the presence of colonic diverticular complications.

Management of spontaneous colonic perforation in Ehlers-Danlos syndrome type IV.

A 14-year-old girl with a family history of fatal colonic rupture, presented with a 2-day history of abdominal pain and signs of peritonitis. At laparotomy, a full-thickness perforation of the sigmoid colon was found, which was exteriorized as a loop colostomy. Subsequently, molecular studies of the patient's cultured fibroblasts found a point mutation in the COL3A1 gene, confirming a diagnosis of Ehlers-Danlos syndrome type IV (EDS-IV). Four and a half years later, a total abdominal colectomy and ileoproctostomy were performed, restoring intestinal continuity. At 5 years follow-up, the patient has had no further complications. Although spontaneous colonic perforation is a well-reported manifestation of EDS-IV, a consensus on the surgical management of this complication in EDS-IV has yet to be determined. Given the high rate of reperforation in EDS-IV when the colon is left in place and the low incidence of reported small bowel and rectal perforations, subtotal colectomy is a reasonable treatment. Primary anastomosis and avoidance of an end-ileostomy was possible in this young patient, with no evidence of anastomotic leakage nor reperforation to date. Lifelong close follow-up should be continued in these patients, because the natural history of this anatomy in EDS-IV is not known.

Sigmoid diverticulitis in identical twins.

Severe sigmoid diverticulitis requiring left colon resection occurred in monozygotic twins during their third decade. An inherited tendency is suggested.

Sigmoid volvulus: new thoughts on the epidemiology.

Sigmoid volvulus usually affects the elderly, but it is being increasingly described in a younger age group. In these patients the diagnosis is often delayed, due to a prolonged and intermittent history. Three patients, of 31,36, and 67 years, are described here, and they demonstrate an increased incidence within families, which has not been previously recognized. Awareness of this possibility may allow earlier diagnosis when investigating young patients with intermittent abdominal symptoms, whose relatives are known to be affected.