Approach

Diagnosis is challenging as the disorder is rarely seen in clinical practice. Careful assessment of physical signs and symptoms, with family history, are helpful, but laboratory and genetic analysis are essential for definitive diagnosis.

History and physical exam

Patients typically present to the pediatrician, as initial signs and symptoms often are displayed in the first few months of life. Parents are phenotypically normal. The diagnosis may still be unknown in other family members because heterozygous loss of microsomal triglyceride transfer protein (MTTP) is tolerated with sufficient function from the wild type allele.

Parents will often note foul-smelling stools and a history of vomiting or abdominal distension. Regular assessment of the patient's stool consistency, odor, and frequency are essential for diagnosis. Suspicion of the diagnosis should arise if the child is displaying faltering growth or developmental delay on routine growth charts (height, weight, head circumference).[1][2]

If the disease is missed and the patient is older, more concerning and progressive symptoms may have evolved, reflecting the deficiency of nutrients, fat-soluble vitamins, and free fatty acids.[2] Neurologic manifestations are due to vitamin A and E deficiencies and include peripheral neuropathy, movement disorders, and ocular disorders such as ophthalmoplegia and retinitis pigmentosa.[1][2][5] Both central and peripheral nervous systems are affected with patients having either upper or lower motor neuron findings.[6] Patients can present with cerebellar dysfunction (e.g., ataxia, dysarthria, dysmetria), as well as compromise of posterior column function with loss of proprioception and deep tendon reflexes.[2][21] The patient or family members may note poor vision, night blindness, ataxia, dysmetria, muscle contractions, dysarthria, and muscle weakness.[2][19] Atypical pigmentary retinopathy with bilateral optic disc swelling has been reported.[22] Symptomatic neuromuscular problems are seen in approximately one third of untreated patients by age 10 years; ataxia generally develops later. Additionally, if anemia has developed secondary to malnutrition, patients may complain of fatigue and may appear pale.

Hepatomegaly from hepatic steatosis may be present.[2]

The definitive diagnosis is likely to be obtained in the subspecialist setting due to increased awareness of the disease and familiarity with necessary testing. Referral to an ophthalmologist, a neurologist, and a gastroenterologist is recommended. An ophthalmologist may find signs of retinal inflammation on examination.[23]

Laboratory assessment

The initial workup typically includes stool sampling, a blood smear, and a fasting lipid panel; however, none of these tests are confirmatory. Due to the rarity of this disease, a genetics test is not usually done initially but is necessary for diagnosis.

Tests to aid/confirm diagnosis include the following.

  • A fasting lipid panel shows very low or absent levels of plasma triglycerides, total cholesterol, very low-density lipoprotein, and low-density lipoprotein, and the absence of apolipoprotein B (apo B).[1]

  • Vitamin A, E, and K levels should also be performed early, as low levels will help confirm diagnosis. (Vitamin D is activated on the skin by ultraviolet rays from endogenously produced metabolites, but levels may still be subnormal). Vitamin E levels are typically undetectable.

  • A blood smear shows anemia and acanthocytes (red blood cells with a star-like appearance).[2][24]

  • Additionally, a stool sample shows increased fat composition.

  • Liver transamininases may be elevated.[2]

  • Clotting tests may display an increased partial thromboplastin time and iron studies may display low iron.

  • An intestinal biopsy is unnecessary for diagnosis; however, it may have been performed in the process of identifying this rare diagnosis. The results may show a characteristic appearance of villus tips with a lacy appearance and lipid droplets within enterocytes.

  • The definitive diagnostic test is assessment of MTTP and requires a lipid disorders or genetic subspecialty lab.

  • Genetic testing for mutations, deletions, or insertions in MTTP gene associated with abetalipoproteinemia confirms the diagnosis in a subject suspected to be affected.[7][10]​​ The apolipoprotein B (apo B) gene should also be screened as homozygous familial hypobetalipoproteinemia can give a similar biochemical and clinical phenotype to abetalipoproteinemia.[7]​ If there are existing genetic test results, do not perform repeat testing unless there is uncertainty about the existing result, e.g., the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[25]

Other tests

If the disease has progressed, direct and indirect ophthalmoscopy by an ophthalmologist may identify retinal degeneration.[23] If the patient begins showing neurologic signs of damage, such as ataxia or intention tremor, a neurologist may perform electrodiagnostic studies.[2] Evoked potentials may display abnormal somatosensory conduction velocity. Conduction velocity may be slowed with decreased amplitude of sensory potentials. Evidence of peripheral nerve demyelination may appear on electromyelogram.[6]

Use of this content is subject to our disclaimer