The exact incidence of CDD differs among populations and geographic areas.
2 Milder forms remain undiagnosed until adulthood.
1,3 CDD includes a large number of conditions. Canani et al.
1,3 suggested that CDD could be classified into 4 groups (). New genes have been identified in relation to CDD.
3 MVID is one of the CDD according to this classification.
1,3 No prevalence data are available. Almost half of 24 patients with MVID in one report were from consanguineous families from the Mediterranean area.
8 Rab8, a small GTP-binding protein, and myosin Vb (MYO5B) were demonstrated to be involved in the intracellular transport of proteins to the apical level of the intestinal epithelial cells.
9 Several mutations in MYO5B and loss of MYO5B function in MVID patients have been described recently.
9-11 MYO5B deficiency may block the apical traffic of intracellular vacuoles containing microvilli, thereby determining aggregation of apically bound vesicles.
9Pregnancy and delivery are usually uneventful. Polyhydramnios is reported in rare isolated cases.
4,12 It causes severe and intractable secretory diarrhea (150-300 ml/kg/day) that usually starts shortly after birth and persists despite total bowel rest,
1,2,4,8,13 resulting in severe dehydration and profound metabolic acidosis.
2,8-10 A late onset form (3-4 months of life) with a better outcome is described.
2 Our patient had a typical presentation. Complete and prolonged bowel rest allows reducing stool volume, but volumes nearly always remain above 150 ml/kg/day.
13 Inappropriate PN with steadily increasing IVF may significantly aggravate stool output. No specific physical findings can be detected apart from abdominal distension with fluid-filled intestinal and colonic loops. There are no malformations or dysmorphic features.
4 Chen et al.
14 recently reported prenatal molecular diagnosis of MVID for the first time. They also demonstrated a high level of amniotic fluid alpha fetoprotein (AFAFP) in the second trimester. They speculated that the AFAFP elevation might possibly be caused by in utero body fluid leakage into the amniotic fluid through fetal enteropathy.
14 Kidney dysfunction may be due to long-term PN, recurrent line infections, nephrotoxic medications and dehydration.
15,16Our patient had renal tubular dysfunction likely due to dehydration initially and line infections and PN later on. The differential diagnosis included osmotic and nonosmotic diarrhea.
1,4 Molecular basis of CDD due to osmotic mechanisms is clearly identified. In the nonosmotic category, only MVID, IPEX syndrome and APS-1 genes are identified so far.
4 Rarely, intestinal pseudo-obstruction syndrome and Hirschsprung’s disease can present as CDD. Microscopy reveals shortened microvilli and villous atrophy with an increased number of secretory granules within enterocytes and membrane-bound inclusions on EM without crypt hyperplasia or inflammation, which was the case in our patient.
5 PAS, alkaline phosphatase and immunohistochemical (pCEA and CD10) stains have proved useful.
6,7 All of these four stains exhibit the same staining pattern and sensitivity, indicating that any method is useful for the diagnosis; particularly the simple and routinely used PAS stain.
In one study
, morphological features together with the biomarker-highlighted apical cytoplasmic blush and inclusions were unique and diagnostic.
17 They suggested that EM is not required to establish a diagnosis if these studies display typical features. As microvilli on immature crypt cells are usually normal, isolated EM of these cells should not be performed as it could lead to false negative results. In addition, the isolated finding of rudimentary or absent microvilli on enterocytes is also not sufficient to diagnose MVID.
4 Our case has substantiated this with its characteristic morphohistochemical and immunohistochemical diagnostic findings and less typical findings on EM. Typical histological findings have been well described in SB biopsies, but there are few reports on their presence in the gastric mucosa.
18 MVID patients are PN dependent. PN in MVID is difficult with frequent complications,
8 and the risk of death or irreversible sequelae is high. SBTx is the only curative treatment.
4,19It can be performed as isolated or combined liver- SBTx, if significant liver disease exists. Early SBTx can be considered as a first choice treatment.
4,19 However, the decision and timing of SBTx are difficult to arrive at because of improvements in long-term PN,
20 and the complications in SBTx.
8,21 Severe diarrhea, dehydration with resulting hypoperfusion can cause neurological and developmental retardation. Impaired renal function, nephrocalcinosis and growth failure are frequent.
4,19 Complications of PN such as cholestasis or liver failure are very frequent. Infectious complications of the central lines are frequent etiologies of death. In one study, all 24 patients over a 14 year period were completely depended on PN.
8 Thirteen children underwent SBTx (9 isolated, 4 combined with liver Tx). Patient survival rates were 63% without SBTx and 77% with SBTx. In an earlier report, 75% of 23 patients in a multicenter survey died of sepsis, liver failure, or metabolic imbalance before 9 months of age.
20 Our patient exhibited severe complications and death as early as 4 months of age, which is typically described.
