Helicobacter pylori - Portal Neonatal

direct functional consequence, in complete intestinal
failure. It has been speculated that the disease
is associated with a disorder of the enterocyte
cytoskeleton, which produces an abnormal assembly
of microvilli. Intestinal microvillus dystrophy
was reported as being a hypothetic variant of
MVID. 24 The underlying pathogenesis of MVID is
still unclear, although a cytoskeletal myosin deficiency
has been found. 25 When analyzing the
turnover of sucrase-isomaltase, as a representative
brush-border protein, there is clear evidence that
the direct and indirect constitutive pathways are
intact in MVID. 21 Therefore, a defect in endocytosis
is rather unlikely. More recently, by investigating
the glycobiological nature of the epithelial
accumulation of PAS, Phillips et al 26 suggested
that MVID involves a defect in exocytosis of the
glycocalyx. 26 The absence of glycocalyx might
impair normal cell functions.
Considering the number of cases with affected
siblings, and the frequency of consanguinity
among patients in families of affected infants, this
disease appears to be transmitted as an autosomal
recessive trait. 13,15,27 No candidate gene has been
identified to date. MVID has been reported in a girl
with autosomal dominant hypochondroplasia. 28
The gene defect of this disease was recently localized
on the chromosome region 4p16.3, which
might help in elucidating the genetic basis of MVID.
Long-term outcome
MVID is a congenital constitutive intestinal epithelial
cell disorder leading, in its typical early-onset
form, to permanent intestinal failure. The largest
multicenter survey, of 23 MVID patients, 15
revealed an extremely reduced life expectancy
with a 1-year survival rate of less than 25%. Most
children died of septic complications, liver failure,
or metabolic decompensation. Few cases of MVID,
especially with the late-onset form, may survive
with limited stool output and may require only
partial PN. 29 Treatment with corticosteroids,
colostrum or epidermal growth factor has not been
successful, but octreotide has been used with
partial success in one patient. 15 In contrast to the
initial outcomes before the 1980s, PN now allows
most infants and children to survive. However,
complications related to inadequate PN do limit
long-term survival. These include recurrent
Microvillus inclusion disease 5
catheter-related sepsis, extensive thrombosis, fat
overload syndrome and cholestasis. In addition,
without evidence of an associated renal disease,
some of these infants and children present chronic
hydro-electrolytic imbalance and acidosis, with
subsequent impaired length growth. Others,
because of repeated dehydration episodes associated
with unadapted phosphocalcic intakes,
present with nephrocalcinosis. Finally, even with
adequate long-term PN and normal growth, most
children remain with high and uncomfortable
stool output. This requires daily fluid replacement
with the high risk of severe dehydration. Intestinal
transplantation therefore became the only definitive
treatment of this rare intestinal disease. 30–33
Definitive treatment
Since the introduction of tacrolimus (originally
FK506) as an immunosuppressive drug after organ
transplantation in the early 1990s, the outcome of
intestinal transplantation markedly improved.
Several cases of successful transplantation for
MVID have been reported. 30–35 Transplantation
involved isolated intestine, 30–33 or intestine
combined with the liver. 31,32 Following the report
of these cases, there has been an ongoing discussion
on whether or not the colon should be transplanted
together with the small bowel.
We recently evaluated the possibility and outcome
of intestinal transplantation in ten consecutive
patients with early-onset congenital MVID at
Necker-Enfants Malades Hospital (Paris) (Ruemmele
et al, submitted for publication). Two
patients died before they could be put on a waiting
list for small-bowel transplantation; one patient is
still waiting. We performed cadaveric intestinal
transplantation in seven patients aged between 3
and 11 years by using tacrolimus, steroids and
interleukin (IL-2) blockers. Three transplantations
were performed with isolated intestine, and four
with intestine associated with the liver. Right
colon transplantation was performed in five cases
(two with isolated intestine). One patient died
during transplantation surgery from acute liver
failure and hemodynamic shock, probably due to
re-perfusion shock. The six others (86%) survived,
with a median follow-up of 3 years (range 1–8
years). Graft rejections occurred in two patients
(one with isolated intestinal transplantation, and