LYMPHANGIECTASIA AND ABETALIPOPROTEIN
DEFICIENCY
Intestinal lymphangiectasia is an unusual disorder characterized by dilated lymphatic channels in the mucosa, submucosa, or subserosa of the small intestine, leading to protein-losing enteropathy. Waldman originally described an idiopathic form, primary intestinal lymphangiectasia; however, obstruction to the flow of lymph in certain cardiac diseases or hematologic malignant diseases and retroperitoneal lymph node enlargement due to chemotherapeutic, infectious, or toxic agents can secondarily lead to lymphangiectasias that present in the same manner as primary intestinal lymphangiectasia.
The
worldwide prevalence of intestinal lymphangiectasia is not well known. It
primarily affects children but is also seen in adults. Primary intestinal
lymphangiectasia appears to occur sporadically, but reports of familial
clustering suggest an underlying genetic role; a rare mutation in genes that
regulate lymphogenesis has been identified.
Primary
intestinal lymphangiectasia arises from malformation or hypoplasia of lymphatic
channels, which impairs lymph flow. Chronic obstruction regardless of the cause
increases intraluminal pressure in lymphatic channels, with resultant
dilatation of the submucosal and subserosal lymphatic vessels in the intestine.
Ultimately, these cystic dilations rupture, allowing leakage of intestinal
lymph into the intestinal lumen. As a result, there is excessive loss of serum
proteins and lymphocytes into the gastrointestinal tract, and absorption of
chylomicrons and fatsoluble vitamins is impaired.
The
most common symptoms are nonspecific and include fatigue, weight loss, and
failure to thrive; intermittent diarrhea or steatorrhea with nausea and
vomiting can be seen. Peripheral edema is often present, and ascites, pleural
effusion, or even anasarca can develop. Laboratory features reflect a
protein-losing enteropathy with low levels of serum albumin, gamma globulins,
transferrin, and ceruloplasmin. Clotting factors are frequently reduced, but
this rarely causes complications. Lymphopenia, as previously mentioned, is a
common feature, and deficiencies of fat-soluble vitamins may develop. The
presence of protein-losing enteropathy can be demonstrated by measurement of
alpha-1 anti-trypsin clearance.
CT
enterography may show a characteristic halo sign, and MRI can also be
suggestive; however, the diagnosis of intestinal lymphangiectasia is based on
endoscopy findings and is confirmed by histologic examination. Capsule
endoscopy provides complete examination of the small intestine, but the
inability to obtain samples is a drawback. On endoscopy, lymphangiectasias
appear as white spots overlying the mucosa, described as a snowflake
appearance.
Histopathologic examination of
biopsies shows markedly dilated lymphatic channels most apparent at the tips of
the mucosal villi, with polyclonal plasma cells con- firming the presence of
intestinal lymphangiectasia.
The
treatment of intestinal lymphangiectasia involves maintenance of nutrition and
treatment of any underlying disorder. A diet rich in protein and low in fat is
recommended to lessen lymphatic flow. Supplementation of medium-chain
triglyceride (which is directly absorbed in the portal venous circulation,
bypassing the intestinal lymphatics) provides extra energy and lessens lacteal
congestion and lymph loss. In severe cases, total parenteral nutrition may be
needed. Use of octreotide and tranexamic acid has been reported, and segmental small
bowel resection for localized areas of lymphangiectasia may be beneficial.
Abetalipoprotein
Deficiency
Abetalipoproteinemia
is a rare, autosomal recessive disorder, caused by a mutation in the transfer
protein responsible for assembly of apolipoprotein B (apoB) and lipids in the
liver and intestine. It is characterized by fat malabsorption, acanthocytosis,
and hypocholesterolemia. Hypobetalipoproteinemia is another rare inherited
disorder that results from improper packaging and secretions of apoB-containing
lipoproteins.
Both
disorders are characterized by defective secretion and transport of lipids that
leads to intestinal fat malabsorption and fat-soluble vitamin deficiencies. If
left untreated, they have profound consequences,
including
the development of retinitis pigmentosa, coagulopathy, posterior column
neuropathy, and myopathy. Hepatic steatosis is also common. Clinical diagnosis
is based on symptoms of chronic diarrhea and failure to thrive during infancy.
Acanthocytosis on blood smear, and the virtual absence of apoB-containing
lipoproteins in the case of abetalipoproteinemia, is diagnostic. Endoscopic
examination performed while the patient is consuming a normal fat diet reveals
a white studded appearance of the intestinal mucosa. Histologic study of
biopsied specimens shows distended enterocytes with a clarified cytoplasm that
stains strongly positive with oil red O owing to the presence of intracellular
neutral lipid.
The prognosis is good when the diagnosis is made early and the patient is maintained on the proper low-fat diet with adequate vitamin supplementation.
