ABETALIPOPROTEINEMIA

·         AR

·         Associated mutations of the microsomal triglyceride transfer protein (MTP) gene

·         a.k.a. Acanthocytosis & Bassen-Kornzweig Syndrome

·         Pathology-

§  Failure to synthesize apolipoprotein B.

§  Lipolysis, micelle formation & Fatty acid uptake & reesterification is normal, but there is failure of removal of reesterified triglyceride from the epithelial cells due to absence of chylomicrons.

§  Lipid Membrane defects (acanthocytes/burr cells)

·         Histology- Normal mucosa appearance but postprandial appearance of vacuolated epithelial cells containing lipid (the vacuoles disappear following a prolonged period of either fat-free intake or fasting)

·         Clinical Features-

§  Present since birth

§  Severe fat malabsorption

§  <1 yr-

§   Failure to thrive & distention of abdomen.

§  Foul smelling, pale & bulky stools.

§  Rickets (mainly, due to steatorrhoea induced calcium loss & also due to Vit D deficiency)  

§  >10 yrs- (due to Vit E deficiency)

§  ↓IQ & Peripheral Neuropathy (first sign-loss of deep tendon reflexes)

§  Loss of position & vibration sense + Ataxia + intentional tremors (due to involvement of dorsal columns, cerebellum & basal ganglia)

§  In Adolescence-(due to Vit E deficiency) atypical Retinitis Pigmentosa (first sign- ↓night & color vision)

§  3^rd-4^th  decade- Severe ataxia & spasticity + complete blindness

§  Death by 5^th decade.

·         Diagnosis-

§  Peripheral blood smear- Acanthocytes

§  Plasma biochemistry-

§  Plasma Cholesterol Levels- ↓↓ (<50mg/dl)

§  Plasma Triglyceride Levels - ↓↓ (<20mg/dl)

§  Complete absence of apoB containing lipoproteins (chylomicrons, VLDL & LDL) from plasma.

§  Small Intestinal biopsy

·         Treatment

§  Large supplements of the fat-soluble vitamins A, D, E, and K [Vitamin E (100-200 mg/kg/24 hr) and vitamin A (10,000-25,000 IU/day) to arrest neurological & retinal degeneration]

§  Intake of medium-chain triglycerides to supplement the fat intake.