PEDBASE.org - The Pediatric Database - Detailed information of ABETALIPOPROTEINEMIA

ABETALIPOPROTEINEMIA

DEFINITION:

A disorder of lipid metabolism characterized by fat malabsorption, acanthocytosis, retinopathy, and progressive neurologic disease.

EPIDEMIOLOGY:

incidence: rare
age of onset:
- 1st year (gastrointestinal manifestations)
- first 10 years (neurologic and ocular manifestations)
risk factors:
- familial - autosomal recessive
  - chrom. #: ?2p24
  - gene: ?
- M > F (3:2)

PATHOGENESIS:

1. Background

cholesterol and triglycerides are transported in the circulation in macromolecular complexes called lipoproteins
the protein component of lipoproteins are called apolipoproteins
abetalipoproteinemia is considered to be a defect in the absorption and transport of lipids
heterozygotes are asymptomatic

2. Genetic Defect

genetic defect -> decreased availability of apolipoproteins B (apo B-100, apo B-48) -> inhibits the formation of chylomicrons (lipoproteins containing exogenous cholesterol and triglycerides) and very low density lipoproteins (lipoproteins containing endogenous cholesterol and triglycerides) -> inhibits availability of cholesterol and triglycerides -> clinical manifestations:

1. Gastrointestinal

malabsorption of fats and fat-soluble vitamins:
- anemia and coagulopathy
- night blindness and retinopathy

2. Peripheral Nervous System

axonopathy and demyelination of peripheral sensory and motor nerves and within the posterior column of the spinal cord -> sensory and motor deficits

3. Hematological

decreased levels of cholesterol and triglyceride in the plasma may result in the maldistribution of lipids within the plasma membrane of the RBC's resulting in RBC membrane deformities -> thorn-like projections (acanthocytosis)

CLINICAL FEATURES:

1. Gastrointestinal Manifestations

initially present from newborn period to 1 year of age

1. Malabsorption Syndrome

fat malabsorption:
- steatorrhea - pale, foul-smelling, bulky stool
- abdominal distention, vomiting, diarrhea, failure to thrive
- malabsorption of fat-soluble vitamins - E, A, K - (vitamin D absorption does not appear to be affected)

2. Neurological Manifestations

begin in the first or second decade and are progressive
first neurological sign is loss of deep tendon reflexes within the first few years of life

1. Sensory Disturbances

altered position and vibration senses
altered pinprick and temperature sensations
stocking-glove distribution of hypesthesia
tend to precede ataxia

2. Movement Disorders

cerebellar ataxia:
- gait disturbances:
  - 33% of patients by 10 years of age
  - 100% of patients by 30 years of age
  - loss of ambulation by 3rd decade
- dysarthria
- dysdiadochokinesia
- dysmetria
chorea
intention tremors

3. Others

muscle weakness
muscle contractions:
- pes cavus, equinovarus, kyphoscoliosis
mental retardation
peripheral neuritis

3. Hematological Manifestations

likely secondary to malabsorption

1. Anemia

hemolytic etiology with iron and/or folate deficiencies
may be associated with hyperbilirubinemia

2. Coagulopathy

prolonged PT

4. Ophthalmologic Manifestations

1. Night Blindness

usually initial symptom (Vitamin A deficiency)

2. Pigmentary Retinal Blindness

most prominent symptom and present by 10 years of age

3. Impaired Visual Acuity

by 10 years of age and may progress to blindness

4. Ophthalmoplegia

dissociated nystagmus on lateral gaze
progressive exotropia

5. Others

cataracts
loss of colour vision
ptosis

INVESTIGATIONS:

1. Serum

blood smear: acanthocytosis of 50-70% of peripheral erythrocytes (thorny projections from cell surface)
reduced cholesterol, triglycerides, beta-lipoproteins, chylomicrons, VLDL. vitamins E, A, and K
lack of apolipoprotein B
anemia (mild to severe) with slight reticulocytosis and negative
Coombs test
low ESR, prolonged PT

2. Biopsies

1. Duodenal

yellowish discolouration of mucosa (increased lipid content)
normal villi
lack of apolipoprotein B on immunofluorescence

2. Peripheral Nerves

paranodal demyelination

3. Electrodiagnostic Studies

1. Evoked Potentials

abnormal somatosensory conduction velocity

2. Conduction Velocity

slowed with decreased amplitude of sensory potentials

3. EMG

denervation

MANAGEMENT:

1. Diet

restriction of long-chain fatty acids
supplement with MCT oil
tends to alleviate the gastrointestinal manifestations

2. Medical

1. Fat Soluble Vitamins

Vitamin E:
- can prevent or retard the neurological manifestations and retinopathy
Vitamin K:
- corrects coagulopathy
Vitamin A:
- corrects night blindness

2. Iron or Folate Supplementation

for anemia

Pediatric Database - ABETALIPOPROTEINEMIA

Pediatric Organization - Pedbase [at] Gmail.com