U01.01.127 Abetalipoproteinemia

Abetalipoproteinemia is a rare autosomal recessive disorder caused by a mutation in the gene encoding the microsomal transfer protein (MTP). This condition disrupts the synthesis and secretion of lipoproteins, leading to malabsorption of dietary fats and fat-soluble vitamins.

Key Features

Pathophysiology

Genetic Inheritance: Autosomal recessive.
Molecular Defect: Mutation in the MTP gene affects lipoproteins’ assembly.
Consequences:
- Absence of chylomicrons, VLDL, and LDL in circulation.
- Deficiency in ApoB-48 and ApoB-100.

Clinical Presentation

Early Manifestations:
- Severe fat malabsorption.
- Steatorrhea.
- Failure to thrive in infancy.
Later Manifestations:
- Retinitis pigmentosa.
- Spinocerebellar degeneration due to vitamin E deficiency.
- Progressive ataxia.
- Acanthocytosis (abnormal red blood cells with spiked membranes).

Diagnostic Findings

Intestinal Biopsy: Lipid-laden enterocytes.

Management

Aspect	Treatment Strategy
Dietary Modifications	Restriction of long-chain fatty acids.
Vitamin Supplementation	High doses of oral vitamin E.

Points to Remember

Deficient Lipoproteins: Chylomicrons, VLDL, and LDL are absent due to defective ApoB-48 and ApoB-100.
Vitamin E Deficiency: Central to many symptoms (e.g., spinocerebellar degeneration, retinitis pigmentosa).
Characteristic Biopsy Finding: Lipid-laden enterocytes in the intestinal mucosa.
Treatment Focus: Diet and vitamin supplementation (especially vitamin E).

Summary Table

Feature	Details
Genetic Basis	Autosomal recessive, MTP gene mutation.
Absent Lipoproteins	Chylomicrons, VLDL, LDL.
Clinical Signs	Fat malabsorption, steatorrhea, failure to thrive, progressive ataxia, retinitis pigmentosa, acanthocytosis.
Complications	Spinocerebellar degeneration, vitamin E deficiency.
Diagnosis	Lipid-laden enterocytes on biopsy.
Treatment	Long-chain fatty acid restriction, oral vitamin E.

USMLE Step 1 Tip

Focus on vitamin E deficiency and its neurological implications, as they are high-yield topics for clinical scenarios related to abetalipoproteinemia.

USMLE Step 1 Review Series

Curriculum