Download Microvillus Inclusion Disease

Microvillus Inclusion Disease- A Deadly Masquerader
Christine Beeson BA OMSIII, Jeffrey C. Weiss MD,
Robert D. Ligorsky DO MACOI FACP FAHA
Objective:
Case Description:
Discussion:
To raise awareness of this disorder
so that recognition of this deadly
disease can be made early, and to
further research in an attempt to
find a cure.
A Navajo female infant presented
to Phoenix Children’s Hospital on
day 6 of life with watery diarrhea.
Pregnancy and delivery were
unremarkable. Family history was
noncontributory for metabolic or
gastrointestinal disorders.
Physical exam revealed a
markedly dehydrated infant in
apparent distress with massive
liquid, almost urine-like stools.
Stool volume quantification found
large losses ranging from
100-500 mL/kg/day. She was
found to have developed
metabolic acidosis. The diarrhea
persisted despite complete bowel
rest. The stool electrolytes were
high in Na and low in K,
consistent with a secretory
diarrhea. TPN and intravenous
fluids were administered, but the
stool volume still remained high.
Several tests were done to detect
a gamut of metabolic, infectious,
immunologic, and hormonal
causes of diarrhea, all of which
were unremarkable. A small
bowel biopsy revealed features
consistent with MVID.
This case of MVID illustrates the value of rapid diagnosis and
treatment. There is increased prevalence of MVID in groups with
consanguineous parents. Populations in England, the Middle
East, and in the Navajo Indians have an increased incidence of
this rare disease. The differential diagnosis includes chloridelosing diarrhea, enzyme/micronutrient deficiencies, congenital
short bowel, tufting disease, and defective sodium-hydrogen
exchange. Clinical diagnosis is made by duodenal biopsies
demonstrating complete villous atrophy, vacuolated cytoplasm,
and alkaline phosphatase-positive inclusions in the apical
cytoplasm. Light microscopy demonstrates abnormal PASpositive material in the apical cytoplasm, and electron
microscopy illustrates microvillus inclusions and an absent
brush border. Intestinal failure and associated diarrhea cannot
be cured and infants are totally dependent on parenteral
nutrition. Metabolic decompensation, dehydration, recurrent
infections, and complications involving the liver and kidneys
make long-term outcomes poor. These patients are candidates
for small bowel transplantation and should be managed in
centers that are equipped to perform the necessary procedures.
Introduction:
Microvillus Inclusion Disease
(MVID) is a rare autosomal
recessive disorder that was first
described by Davidson in 1978.
Mutations in the MYO5B gene
located on chromosome 18 have
been found in most patients
resulting in loss of function of the
myosin Vb5protein. As a result
intestinal microvilli cannot be
properly formed. The disorder most
often presents as life-threatening
diarrhea in newborns, leading to
massive dehydration and
electrolyte imbalance. Total
parenteral nutrition (TPN) is
required to maintain life until a
small bowel transplant can be
performed. In some patients
lifelong nutritional support is
necessary. Complications of
parenteral nutrition can have a
major impact on survival.
Normally, vesicles from the Golgi (Go) carry brush
border components to the cell surface for assembly
(open arrow). This path may be blocked in MVID,
leading to retention of vesicles (VB), giving rise to
microvillus inclusions (MI). Nu=nucleus, Ly=lysosome
References:
1. Cutz E, Sherman PM, Davidson GP. Enteropathies associated with protracted diarrhea of infancy:
clinicopathological features, cellular and molecular mechanisms. Pediatric Pathology & Laboratory
Medicine May-June 1997;17(3):335-67.
2. Erickson RP, Larson-Thomé K, Valenzuela RK, Whitaker SE, Shub MD. Navajo microvillous
inclusion disease is due to a mutation in MYO5B. American Journal Medical Genetics A. 2008;146A:
3117–3119.
3. Ruemmele F, Schmitz J, Goulet O. Microvillous inclusion disease (microvillous atrophy). Orphanet
Journal Of Rare Diseases. January 2006;1:22-5.
Transmission electron micrograph of surface enterocyte
showing microvillus inclusions (MI) with inwardly facing
brush border microvilli (arrow).
Acknowledgements:
Thank you to Dr. Chris Spiekerman, Dr. Robert Ligorsky, and Dr. Jeffrey Weiss for the
production, support, and revision of this poster presentation.