A seven weeks old infant was admitted to hospital with a history of ‘failure to thrive’. A full blood count was performed with the following results:
Hb 123 g/L, WBC 10.2 x 109/L Platelets 586 x 109/L
Examination of the blood film revealed a marked number of acanthocytes. A provisional diagnosis of abetalipoproteinaemia was made.
The following chemistry tests were performed:
|Cholesterol||1.4 mmol/L||NR (3.0-5.5)|
|Triglyceride||<0.1 mmol/L||NR (<2.0)|
|Apolipoprotein A1||0.78 g/L||NR (1.10-2.00)|
|Apolipoprotein B||0.07 g/L||NR (0.60-1.25)|
|Vitamin A||0.4 umol/L||NR (0.5-1.8)|
|Vitamin E||<1 umol/L||NR (5-14)|
|Faecal fat||38 mmol/day||NR (0-3.4)|
The above results confirmed a diagnosis of abetalipoproteinaemia.
Abetalipoproteinaemia is a rare autosomal recessive disorder characterised by the presence of acanthocytic red cells in the peripheral blood. The primary defect is due to a mutation and lack of activity in the microsomal triglyceride transfer protein needed to bind lipids to the ?-apolipoprotein in plasma. Intestinal absorption of lipids is defective. The plasma levels of cholesterol and triglyceride are extremely low and ?-apolipoprotein undetectable. There is an increase in sphingomyelin in the outer half of the red cell membrane bilayer increasing the surface layer of the cell. This ?-apolipoprotein defect leads to the production of acanthocytic red cells, about 50-90% of the red cells being acanthocytes. The sphingomyelin accumulates with cell ageing thus the nucleated precursor red cells and reticulocytes are not affected while the older red cells are affected.
As a result of fat malabsorption and the absence of low density lipoproteins, which transport vitamin E, the red cells of patients with abetalipoproteinaemia are markedly deficient in vitamin E. The level of vitamin A is also reduced.
Abetalipoproteinaemia usually presents in early childhood with diarrhoea and failure to thrive and is characterised clinically by fat malabsorption, spinocerebellar degeneration, pigmented retinopathy and acanthocytosis. The initial neurologic manifestations are loss of deep-tendon reflexes, ataxia and development of a spastic gait. They also develop retinitis pigmentosa which ultimately progresses to near-blindness. The neurological abnormalities present between five and ten years of age and continue until death in the second or third decade. Despite the marked acanthocytosis and vitamin E deficiency seen in these patients, anaemia and haemolysis are mild. The haemoglobin levels are invariably normal.
Treatment consists of a low-fat, high caloric, vitamin-enriched diet accompanied by large supplemental doses of vitamin E. It is imperative that treatment be initiated as soon as possible to delay the onset of the neurological symptoms. New therapies for this debilitating disease are needed.