Bassen-Kornzweig syndrome

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.

Diagnosis

The initial observations that leads a physician to suspect a fat digestion problem is that affected babies have severe stomach problems with a high level of fats detected in the stool; the stool is often pale and foul smelling. One of the first medical tests usually performed on infants with failure to thrive is a complete blood count (CBC), which shows abnormal, thorny-shaped red blood cells (acanthocytes) that can be visualized using a microscope. A lipid profile demonstrates low levels of total cholesterol and low concentrations of VLDL and LDL in the blood. Apolipoprotein B can be completely absent or detected in reduced amounts in the blood. Due to the inability to digest fats, loss of fat-soluble vitamins such as vitamin A, D, E, or K occurs and can result in a deficiency. An examination by an ophthalmologist might show retinal degeneration leading to visual loss. A neurologist might find nerve demyelination (degeneration of the protective layer of the nerve) by performing nerve conduction studies or an EMG. Loss of peripheral nerves can be associated with ataxia (abnormal muscle coordination).

Treatment team

In addition to consistent evaluation by an experienced neurologist, it is important to consult with a nutritionist regarding the appropriate dietary restriction, as this can influence the development and well being of an affected individual. There is also a requirement for large doses of fat-soluble vitamin supplements because there is an inability to digest fat from the diet; the body does not retain these vitamins. Because the child with Bassen-Kornzweig syndrome often suffers from hypotonia and ataxia, an experienced physical therapist can often help develop strategies to treat the associated symptoms.

Treatment

Persons with Bassen-Kornzweig syndrome are treated primarily to lessen symptoms. The most formidable approach to treatment is dietary restriction and supplementation with the appropriate vitamins (D, E, A, and K) as well as with fats that can be broken down more easily. Supplementation with fat-soluble vitamins may slow the progression of the retinal degeneration. As these patients can develop movement disorders such as tremors , chorea (uncontrollable shaking), difficulty talking (dysarthria ), and difficulty with tasks that require coordination, speech and occupational therapy is recommended and can be helpful.

Recovery and rehabilitation

Due to the nature of Bassen-Kornzweig syndrome and the biochemical defects, treatment is based solely on monitoring the diet and treating symptoms as well as any biochemical abnormalities that might develop. Currently, there is no cure.

Clinical trials

The National Heart, Lung, and Blood Institute (NHLBI) and the National Institutes of Health (NIH) are sponsoring a clinical trial to investigate circulating lipoproteins in the blood in order to better understand fat metabolism and the role it plays in heart disease. As part of the ongoing studies, healthy patients will receive injections of controlled doses of isolated and purified lipoproteins, along with a specially formulated diet. Patients will have blood drawn and a urinalysis and be monitored during the study. Contact information: National Heart, Lung and Blood Institute (NHLBI), 9000 Rockville Pike, Bethesda, Maryland, 20892; Patient Recruitment and Public Liaison Office (800) 411-1222; e-mail: prpl@mail.cc.nih.gov.

Prognosis

The prognosis depends on the severity of the neurological impairments, which can vary from patient to patient. There have been cases of severe, progressive neurological damage occurring before the person reaches age 30. Neurological damage is irreversible. The visual problems can also be progressive and the extent of retinal degeneration and visual loss can be variable. Mental deterioration can also sometimes occur.

Special concerns

An important consideration for these patients is dietary restriction. Due to the inability to digest dietary fats, the diet of persons with Bassen-Kornzweig syndrome should contain no more than five ounces of lean meat, fish, or chicken per day. This will help mitigate unpleasant intestinal symptoms. Certain high fat foods should be avoided, or foods that contain long-chain triglycerides (fat-containing molecules that are more difficult to breakdown). However, because the body needs some fats, as fat is important for many components of cells and tissues including cell membranes, medium chain triglycerides can be taken to supplement the diet.

All dietary restrictions should be carefully considered by a nutritionist and a physician, and the patient should be monitored for symptoms and responses to such treatments. Failure to supplement with vitamins such as vitamin E can lead to a vitamin deficiency. Vitamin E deficiency is associated with poor transmission of nerve impulses, hypotonia (weak muscles), and retinal degeneration leading to blindness. For these reasons, it is important to supplement with the appropriate vitamins at a dose recommended by a physician.

Resources

PERIODICALS

Rader, D. J., et al. "Abetalipoproteinemia: New Insights into Lipoprotein Assembly and Vitamin E Metabolism from a Rare Genetic Disease." JAMA, vol. 270, no. 7 (1993): 865–869.

OTHER

"A-Beta-Lipoproteinemia." Genetic Information and Patient Services, Inc (GAPS). March 10, 2004 (April 27, 2004). <http://www.icomm.ca/geneinfo/abl.htm>.

National Institutes of Health. "Bassen-Kornzweig Syndrome. "Medline Plus. March 10, 2004 (April 27, 2004). <http://www.nlm.nih.gov/medlineplus/ency/article/001666.htm>.

ORGANIZATIONS

Abetalipoproteinemia Support Group. 14252 Culver drive #543, Irvine, CA 92604. abetalipoproteinemia@yahoogroups.com. <http://groups.yahoo.com/group/Abetalipoproteinemia>.

CLIMB (Children Living with Inherited Metabolic Diseases). The Quadrangle, Crewe Hall, Weston Road, Crewe, Cheshire, CW1-6UR, United Kingdom. (127) 0 2-50221. Lesley@climb.org.uk. <http://www.CLIMB.org.uk>.

Foundation Fighting Blindness. Executive Plaza 1, 11350 McCormick Road, Suite 800, Hunt Valley, MD 21031-1014. (410) 785-1414 or (888) 394-3937. jchader@blindness.org. <http://www.blindness.org>.

Retinitis Pigmentosa International. 23241 Ventura Boulevard, Suite 117, Woodland Hills, CA 91364. (818) 992-0500. <http://groups.yahoo.com/group/Abetalipoproteinemia>.

Bryan Richard Cobb, PhD