Bassen-Kornzweig Syndrome Health Article

Definition

Bassen-Kornzweig syndrome is a rare genetic disorder that is characterized by an inability to properly absorb dietary fats, resulting in neurological abnormalities, degeneration of the retina of the eye, a typical red blood cell abnormality ("burr-cell" malformation), and failure to thrive (grow and gain weight) during infancy.

Description

Bassen-Kornzweig syndrome is inherited as an autosomal recessive disorder, which means that parents of affected individuals are themselves unaffected carriers, and that they have a 25% risk of having an affected child in each pregnancy. Alternate names for this disorder include abetalipoproteinemia, acanthocytosis, and apolipoprotein B deficiency. Affected individuals can have severe, irreversible neurological impairments, especially if untreated. Psychological counseling for parents and family members is often helpful. There are support groups that are useful in learning more about other families with affected individuals and how they manage in terms of coping mechanisms, responses to treatment, as well as practical considerations such as lifestyle changes. As the recurrence risk for this disorder is high, genetic counseling is recommended. In some families, prenatal diagnosis is possible.

Demographics

For unclear reasons, males are affected with Bassen-Kornzweig syndrome with greater frequency (70%) than girls, which is uncharacteristic in most autosomal recessive conditions. A majority of the originally described patients (including the first case of an 18-year old girl in 1950) were of Jewish descent. Bassen-Kornzweig syndrome is a rare disorder; estimations of how often it occurs are limited because the responsible genetic mutations were only recently identified and there is more than one gene that contributes to the disorder.

Causes and symptoms

Mutations in two genes have been shown to cause Bassen-Kornzweig syndrome: apolipoprotein B (APOB) and microsomal triglyceride transfer protein (MTP). These proteins are an important part of fat-containing molecules called lipoproteins in the blood. Several of these lipoproteins, such as low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL), are found in either very low concentrations or are completely absent in the blood. These lipoproteins function to transport fat and are important in fat metabolism. Not having these important lipoproteins can result in malabsorption (poor absorption) of fats, and excessive and wasteful fat excretion in the bile called steatorrhea.

MTP is a gene that encodes a protein responsible for transporting triglycerides, cholesteryl esters, and components of the cell's surface called phospholipids. Biochemical studies revealed that in biopsies from patients that lack lipoproteins (abetalipoproteinemia) and controls, MTP enzyme activity was only detected in control samples. MTP is expressed in the lumen of the liver and intestine and is not only important for transport of lipoproteins, but also for their assembly.

The body requires fats for healthy nerves and muscles. The symptoms that develop in Bassen-Kornzweig syndrome affect a person's sensory perception, coordinating muscle movements, blood chemistry, and vision. People with Bassen-Kornzweig can develop problems related to sensing temperature and touch, particularly on the hands and feet, a condition called hypesthesia. The inability to produce lipoproteins leads to several symptoms that can adversely affect infants, who show signs of failure to grow and gain weight, and have fatty, foul-smelling stools that appear to be pale and frothy. A protruding abdomen can often be observed. Brain involvement can be significant, leading to developmental motor delay. Muscle coordination becomes compromised, usually after the child reaches 10 years old. Children with Bassen-Kornzweig syndrome also can have slurred speech that is likely to be secondary to the neurological impairment. Abnormal curvature of the spine, progressively diminished visual abilities, and balance difficulties can also be symptoms experienced by these patients. Finally, affected individuals can develop poor eyesight due to retinitis pigmentosa, along with cataracts and difficulty maintaining eye control.

In Bassen-Kornzweig syndrome, lacking the appropriate concentration of lipoproteins due to defective intestinal absorption of lipids can result in low serum cholesterol levels. Low levels of LDL have also been observed in patients with AIDS, certain types of leukemia, and disorders that involve enlargement of the spleen (Gaucher's disease) and should, therefore, not be confused with Bassen-Kornzweig syndrome.