Page 14 - Journal of Special Operations Medicine - Winter 2015

4,6
1
heterozygous form of FHBL is 1:500. When a patient and malabsorption. Acanthocytosis is a distinguishing
presenting for clearance for Special Operations duty is feature on a peripheral blood smear in patients with
found to have very low lipid levels, what are potential ABL and homozygous FHBL. 9,10 This is due to vitamin
diagnoses? Additionally, what things need to be consid- E deficiency, which is vital to the integrity of the red
10
ered in the Special Operations setting, and what kind of blood cell (RBC) membrane. Additionally, patients
workup needs to be initiated prior to clearance? with ABL are at risk of developing neurologic symp-
toms (primarily spinocerebellar ataxia and posterior
4
column neuropathy) and retinitis pigmentosa. The neu-
Diagnosis
rologic symptoms are secondary to deficiencies in the
HBL is defined as plasma levels of total cholesterol, LDL fat-soluble vitamins, namely vitamin E and vitamin A.
8
cholesterol, or total apoB that are lower than the fifth per- Neurologic and ophthalmologic complications in CRD
centile for age- and sex-matched control subjects. The dis- are less severe than in other types of familial hypocho-
2
ease can be divided into primary and secondary causes. The lesterolemia. Hepatic steatosis invariably develops in
10
primary causes include abetalipoproteinemia (ABL), chy- these patients, including patients who are heterozygous
lomicron retention disease (CRD), and FHBL. The former for FHBL. This is due to the inability of hepatocytes to
two are transmitted recessively, while the latter is inherited secrete fat. There are case reports of patients who go on
in a codominant fashion. The diagnosis of FHBL is further to develop cirrhosis and liver failure. 9
3
segregated into patients with homozygous mutations and
those with heterozygous mutations. Primary HBL diseases Patients with homozygous FHBL are clinically indistin-
2
are due to a variety of genetic mutations. ABL is due to de- guishable from those with recessive HBLs. It is thought
fects in the microsomal triglyceride transfer protein (MTTP) that the majority of patients with heterozygous FHBL
gene, while CRD is associated with defects in the secretion are asymptomatic or mildly symptomatic. Many are di-
1,2
associated, Ras related GTPase 1B (SAR1B) gene. Both agnosed later in life via routine lipid screening, as with
9
ABL and CRD are characterized by enterocytes that are our patient, or are never diagnosed at all. Of those who
unable to produce chylomicrons. Consequently, affected become symptomatic, the most common symptom is
individuals are unable to absorb dietary fat and fat-soluble loose stools due to steatorrhea. Many of these patients
vitamins. Presentation is usually severe and is typically seen will develop elevations in their liver enzymes secondary
4
5,7
2
in infancy or childhood. FHBL is caused most frequently to hepatic steatosis. Neurologic and ophthalmologic
by mutations in apoB, resulting in a protein that is trun- complications are rare.
cated to less than the normal 4,536 amino acid residues.
Almost 60 different mutations have been described in the Long-term Follow-up
etiology of FHBL, most of which are point mutations lead-
ing to splicing errors or premature truncations. Homo- There are suggested guidelines for follow-up of patients
5,6
zygous FHBL is clinically indistinguishable from ABL. The with ABL and homozygous FHBL. The primary aim
6,9
majority of patients with FHBL are heterozygotes and are of these is to ascertain the presence of neurologic and
asymptomatic or mildly symptomatic, with loose stools sec- ophthalmologic findings prior to advanced manifesta-
ondary to mild fat malabsorption. 7 tions, although most of the patients are severely symp-
tomatic at the time of diagnosis. If the diagnosis is made
The secondary causes include strict vegetarianism, other prior to manifestation of the disease, supplementation
disease states causing intestinal fat malabsorption (e.g., of vitamin E and A at higher doses than are usually rec-
sprue, chronic pancreatitis, intestinal lymphangiecta- ommended has been shown to prevent or decrease the
sia), severe liver disease, malnutrition, hyperthyroidism, symptomatology. 6,11
anemia, severe infections, and trauma. 6,8
Follow-up for monitoring patients with heterozygous
The gold standard for diagnosing HBL would be se- FHBL is much less clearly defined. This is likely be-
quencing of the gene suspected as the culprit. However, cause there are no known signs or symptoms that in-
clinical and biochemical diagnoses can be made based on evitably develop in these patients, and because most
the patient’s lipid profile, symptoms, and blood smear of these patients are diagnosed only after routine lipid
4
findings. The organ systems involved in the symptoms, panels reveal the abnormality. Some have suggested an
as well as a thorough family history (if available) and increased life span in these patients due to the decreased
pedigree, can also support the diagnosis. 6 exposure to atherogenic apoB-containing lipoproteins.
While this seems a reasonable theory, there have been
4
no prospective studies to validate this idea. Because of
Clinical Signs and Symptoms
the potential to develop long-term sequelae (although
Patients with the recessive diseases ABL and CRD usu- this is much less common than that seen in the more
ally present in infancy with failure to thrive, steatorrhea, severe forms of HBL), it seems reasonable to have some

2 Journal of Special Operations Medicine Volume 15, Edition 4/Winter 2015