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August 18, 1993, Vol 270, No. 7 >
ARTICLE | August 18, 1993

Abetalipoproteinemia: Title and subTitle BreakNew Insights Into Lipoprotein Assembly and Vitamin E Metabolism From a Rare Genetic Disease FREE

Daniel J. Rader, MD; H. Bryan Brewer, Jr, MD
[+] Author Affiliations

Reprint requests to the Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg 10, Room 7N117, 9000 Rockville Pike, Bethesda, MD 20892 (Dr Rader).


JAMA. 1993;270(7):865-869. doi:10.1001/jama.1993.03510070087042
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Article
References

SELECTED CASE  A 30-year-old woman was referred to the National Institutes of Health (NIH) with malabsorption, ataxia, visual impairment, and low serum cholesterol level. As an infant, she had frequent colic and diarrhea, which improved when the amount of fat in her diet was decreased. She continued to have malabsorptive symptoms after ingesting a fatty meal and was diagnosed at 8 years of age as having celiac disease. A gluten-free diet did not, however, improve her symptoms. During her late teens and twenties, she experienced slowly progressive difficulty maintaining her balance, numbness in her legs below the knee, and difficulty in seeing at night with worsening color vision. At age 28 years she had a small-intestine biopsy; the findings were not consistent with celiac disease but rather revealed lipid-engorged enterocytes. Her family history was remarkable in that her parents were fourth cousins and her three younger sisters had similar, though

REFERENCES

1 +
Bassen FA, Kornzweig AL.  Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. Blood . 1950;;5:381-387.
2 +
Singer K, Fisher B, Perlstein MA.  Acanthrocytosis: a genetic erythrocytic malformation. Blood . 1952;;71:577-591.
3 +
Jampel RS, Falls HF.  Atypical retinitis pigmentosa, acanthrocytosis and heredodegenerative neuromuscular disease. Arch Ophthalmol . 1958;;59:818-820.
4 +
Salt HB, Wolff OH, Lloyd JK, Fosbrooke AS, Cameron AH, Hubble DV.  On having no beta-lipoprotein: a syndrome comprising a-beta-lipoproteinemia, acanthocytosis, and steatorrhoea. Lancet . 1960;;2:325-329.
5 +
Kane JP, Havel RJ.  Disorders of the biogenesis and secretion of lipoproteins containing the B apolipoproteins.  In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease . New York, NY: McGraw-Hill International Book Co; 1989;:1139-1164.
6 +
Ways PW, Parmentier GM, Hayden HJ, Jones JW, Saunders DR, Rubin CE.  Studies on the absorptive defect for triglyceride in abetalipoproteinemia. J Clin Invest . 1967;;46:35-46.
7 +
Sobrevila LA, Goodman ML, Kane CA.  Demyelinating central nervous system disease, macular atrophy and acanthocytosis (Bassen-Kornzweig syndrome). Am J Med . 1964;;37:821-828.
8 +
Wichman A, Buchthal F, Pezeshkpour GH, Gregg RE.  Peripheral neuropathy in abetalipoproteinemia. Neurology . 1985;;9:1279-1289.
9 +
Cogan DG, Rodrigues M, Chu FC, Schaefer EJ.  Ocular abnormalities in abetalipoproteinemia. Ophthalmology . 1984;;91:991-998.
10 +
Caballero FM, Buchanan GR.  Abetalipoproteinemia presenting as severe vitamin K deficiency. Pediatrics . 1980;;65:161-163.
11 +
Levy RI, Fredrickson DS, Laster L.  The lipoproteins and lipid transport in abetalipoproteinemia. J Clin Invest . 1966;;45:531-541.
12 +
Lackner KJ, Monge JC, Gregg RE, et al.  Analysis of the apolipoprotein B gene and messenger ribonucleic acid in abetalipoproteinemia. J Clin Invest . 1986;;78:1707-1712.
13 +
Talmud PJ, Lloyd JK, Muller DP, Collins DR, Scott J, Humphries S.  Genetic evidence from two families that the apolipoprotein B gene is not involved in abetalipoproteinemia. J Clin Invest . 1988;; 82:1803-1806.
14 +
Huang LS, Janne PA, de Graaf J, et al.  Exclusion of linkage between the human apolipoprotein B gene and abetalipoproteinemia. Am J Hum Genet . 1990;;46:1141-1148.
15 +
Dullaart RP, Speelberg B, Schuurman HJ, et al.  Epitopes of apolipoprotein B-100 and B-48 in both liver and intestine: expression and evidence for local synthesis in recessive abetalipoproteinemia. J Clin Invest . 1986;;78:1397-1404.
16 +
Bouma ME, Beucler I, Pessah M, et al.  Description of two different patients with abetalipoproteinemia: synthesis of a normal-sized apolipoprotein 0-48 in intestinal organ culture. J Lipid Res . 1990;;31:1-15.
17 +
Wetterau JR, Aggerbeck LP, Laplaud PM, McLean LR.  Structural properties of the microsomal triglyceride-transfer protein complex. Biochemistry . 1991;;30:4406-4412.
18 +
Wetterau JR, Aggerbeck LP, Bouma ME, et al.  Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science . 1992;;258:999-1001.
19 +
Burton GW, Traber MG.  Vitamin E: antioxidant activity, biokinetics, and bioavailability. Annu Rev Nutr . 1990;;10:357-382.
20 +
Traber MG, Kayden HJ.  Preferential incorporation of alpha-tocopherol vs gamma-tocopherol in human lipoproteins. Am J Clin Nutr . 1989;;49:517-526.
21 +
Traber MG, Kayden HJ.  Vitamin E is delivered to cells via the high affinity receptor for low-density lipoprotein. Am J Clin Nutr . 1984;;40:747-751.
22 +
Kayden HJ, Hatam LJ, Traber MG.  The measurement of nanograms of tocopherol from needle aspiration biopsies of adipose tissue: normal and abetalipoproteinemic subjects. J Lipid Res . 1983;; 24:652-656.
23 +
Traber MG, Sokol RJ, Ringel SP, Neville HE, Thellman CA, Kayden HJ.  Lack of tocopherol in peripheral nerves of vitamin E-deficient patients with peripheral neuropathy. N Engl J Med . 1987;; 317:262-265.
24 +
Kayden HJ, Traber MG.  Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J Lipid Res . 1993;; 34:343-358.
25 +
Traber MG, Lane JC, Lagmay NR, Kayden HJ.  Studies on the transfer of tocopherol between lipoproteins. Lipids . 1992;;27:657-663.
26 +
Kayden HJ, Traber MG.  Clinical, nutritional and biochemical consequences of apolipoprotein B deficiency. Adv Exp Med Biol . 1986;;201:67-81.
27 +
Sokol RJ, Heubi JE, Iannaccone ST, Bove KE, Balistreri WF.  Vitamin E deficiency with normal serum vitamin E concentrations in children with chronic cholestasis. N Engl J Med . 1984;;310:1209-1217.
28 +
Sokol RJ, Kayden HJ, Bettis DB, et al.  Isolated vitamin E deficiency in the absence of fat malabsorption—familial and sporadic cases: characterization and investigation of causes. J Lab Clin Med . 1988;;111:548-559.
29 +
Kayden HJ, Traber MG.  Abetalipoproteinemia and homozygous hypobetalipoproteinemia.  In: Steiner G, Shafrir E, eds. Primary Hyperlipoproteinemias . New York, NY: McGraw-Hill International Book Co; 1990;:249-260.
30 +
Fliesler SJ, Anderson RE.  Chemistry and metabolism of lipids in the vertebrate retina.  In: Holman RT, ed. Progress in Lipid Research . London, England: Pergamon Press Ltd; 1983;:79-131.
31 +
Wetzel MD, Fahlman C, Maude MB, et al.  Fatty acid metabolism in normal miniature poodles and those affected with progressive rod-cone degeneration.  In: LaVail MM, Hollyfield JG, Anderson RE, eds. Progress in Clinical and Biological Research: Degenerative Retinal Disorders: Clinical and Laboratory Investigation . New York, NY: Alan R Liss Inc; 1989;:427-439.
32 +
Linton MF, Farese RV Jr, Young SG.  Familial hypobetalipoproteinemia. J Lipid Res . 1993;;34:521-541.
33 +
Malloy MJ, Kane JP, Hardman DA, Hamilton RL, Dalal KB.  Normotriglyceridemic abetalipoproteinemia: absence of the B-100 apolipoprotein. J Clin Invest . 1981;;67:1441-1450.
34 +
Hardman DA, Pullinger CR, Hamilton RL, Kane JP, Malloy MJ.  Molecular and metabolic basis for the metabolic disorder normotriglyceridemic abetalipoproteinemia. J Clin Invest . 1991;;88:1722-1729.
35 +
Roy CC, Levy E, Green PH, et al.  Malabsorption, hypocholesterolemia, and fat-filled enterocytes with increased intestinal apoprotein B chylomicron retention disease. Gastroenterology . 1987;;92:390-399.
36 +
Pessah M, Benlian P, Beucler I, et al.  Andersen's disease: genetic exclusion of the apolipoprotein-B gene in two families. J Clin Invest . 1991;;87: 367-370.
37 +
Bieri JG, Hoeg JM, Schaefer EJ, Zech LA, Brewer HB Jr.  Vitamin A and vitamin E replacement in abetalipoproteinemia. Ann Intern Med . 1984;;100: 238-239.
38 +
Muller DPR.  Effect of large oral doses of vitamin E on the neurological sequelae of patients with abetalipoproteinemia.  In: Lubin B, Machlin LJ, eds. Vitamin E: Biochemical, Hematological and Clinical Aspects . New York, NY: New York Academy of Sciences; 1982;:133-144.
39 +
Runge P, Muller DPR, McAllister J, Calver D, Lloyd JK, Taylor D.  Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinemia. Br J Ophthalmol . 1986;;70:166-173.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Bassen FA, Kornzweig AL.  Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. Blood . 1950;;5:381-387.
2 +
Singer K, Fisher B, Perlstein MA.  Acanthrocytosis: a genetic erythrocytic malformation. Blood . 1952;;71:577-591.
3 +
Jampel RS, Falls HF.  Atypical retinitis pigmentosa, acanthrocytosis and heredodegenerative neuromuscular disease. Arch Ophthalmol . 1958;;59:818-820.
4 +
Salt HB, Wolff OH, Lloyd JK, Fosbrooke AS, Cameron AH, Hubble DV.  On having no beta-lipoprotein: a syndrome comprising a-beta-lipoproteinemia, acanthocytosis, and steatorrhoea. Lancet . 1960;;2:325-329.
5 +
Kane JP, Havel RJ.  Disorders of the biogenesis and secretion of lipoproteins containing the B apolipoproteins.  In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease . New York, NY: McGraw-Hill International Book Co; 1989;:1139-1164.
6 +
Ways PW, Parmentier GM, Hayden HJ, Jones JW, Saunders DR, Rubin CE.  Studies on the absorptive defect for triglyceride in abetalipoproteinemia. J Clin Invest . 1967;;46:35-46.
7 +
Sobrevila LA, Goodman ML, Kane CA.  Demyelinating central nervous system disease, macular atrophy and acanthocytosis (Bassen-Kornzweig syndrome). Am J Med . 1964;;37:821-828.
8 +
Wichman A, Buchthal F, Pezeshkpour GH, Gregg RE.  Peripheral neuropathy in abetalipoproteinemia. Neurology . 1985;;9:1279-1289.
9 +
Cogan DG, Rodrigues M, Chu FC, Schaefer EJ.  Ocular abnormalities in abetalipoproteinemia. Ophthalmology . 1984;;91:991-998.
10 +
Caballero FM, Buchanan GR.  Abetalipoproteinemia presenting as severe vitamin K deficiency. Pediatrics . 1980;;65:161-163.
11 +
Levy RI, Fredrickson DS, Laster L.  The lipoproteins and lipid transport in abetalipoproteinemia. J Clin Invest . 1966;;45:531-541.
12 +
Lackner KJ, Monge JC, Gregg RE, et al.  Analysis of the apolipoprotein B gene and messenger ribonucleic acid in abetalipoproteinemia. J Clin Invest . 1986;;78:1707-1712.
13 +
Talmud PJ, Lloyd JK, Muller DP, Collins DR, Scott J, Humphries S.  Genetic evidence from two families that the apolipoprotein B gene is not involved in abetalipoproteinemia. J Clin Invest . 1988;; 82:1803-1806.
14 +
Huang LS, Janne PA, de Graaf J, et al.  Exclusion of linkage between the human apolipoprotein B gene and abetalipoproteinemia. Am J Hum Genet . 1990;;46:1141-1148.
15 +
Dullaart RP, Speelberg B, Schuurman HJ, et al.  Epitopes of apolipoprotein B-100 and B-48 in both liver and intestine: expression and evidence for local synthesis in recessive abetalipoproteinemia. J Clin Invest . 1986;;78:1397-1404.
16 +
Bouma ME, Beucler I, Pessah M, et al.  Description of two different patients with abetalipoproteinemia: synthesis of a normal-sized apolipoprotein 0-48 in intestinal organ culture. J Lipid Res . 1990;;31:1-15.
17 +
Wetterau JR, Aggerbeck LP, Laplaud PM, McLean LR.  Structural properties of the microsomal triglyceride-transfer protein complex. Biochemistry . 1991;;30:4406-4412.
18 +
Wetterau JR, Aggerbeck LP, Bouma ME, et al.  Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science . 1992;;258:999-1001.
19 +
Burton GW, Traber MG.  Vitamin E: antioxidant activity, biokinetics, and bioavailability. Annu Rev Nutr . 1990;;10:357-382.
20 +
Traber MG, Kayden HJ.  Preferential incorporation of alpha-tocopherol vs gamma-tocopherol in human lipoproteins. Am J Clin Nutr . 1989;;49:517-526.
21 +
Traber MG, Kayden HJ.  Vitamin E is delivered to cells via the high affinity receptor for low-density lipoprotein. Am J Clin Nutr . 1984;;40:747-751.
22 +
Kayden HJ, Hatam LJ, Traber MG.  The measurement of nanograms of tocopherol from needle aspiration biopsies of adipose tissue: normal and abetalipoproteinemic subjects. J Lipid Res . 1983;; 24:652-656.
23 +
Traber MG, Sokol RJ, Ringel SP, Neville HE, Thellman CA, Kayden HJ.  Lack of tocopherol in peripheral nerves of vitamin E-deficient patients with peripheral neuropathy. N Engl J Med . 1987;; 317:262-265.
24 +
Kayden HJ, Traber MG.  Absorption, lipoprotein transport, and regulation of plasma concentrations of vitamin E in humans. J Lipid Res . 1993;; 34:343-358.
25 +
Traber MG, Lane JC, Lagmay NR, Kayden HJ.  Studies on the transfer of tocopherol between lipoproteins. Lipids . 1992;;27:657-663.
26 +
Kayden HJ, Traber MG.  Clinical, nutritional and biochemical consequences of apolipoprotein B deficiency. Adv Exp Med Biol . 1986;;201:67-81.
27 +
Sokol RJ, Heubi JE, Iannaccone ST, Bove KE, Balistreri WF.  Vitamin E deficiency with normal serum vitamin E concentrations in children with chronic cholestasis. N Engl J Med . 1984;;310:1209-1217.
28 +
Sokol RJ, Kayden HJ, Bettis DB, et al.  Isolated vitamin E deficiency in the absence of fat malabsorption—familial and sporadic cases: characterization and investigation of causes. J Lab Clin Med . 1988;;111:548-559.
29 +
Kayden HJ, Traber MG.  Abetalipoproteinemia and homozygous hypobetalipoproteinemia.  In: Steiner G, Shafrir E, eds. Primary Hyperlipoproteinemias . New York, NY: McGraw-Hill International Book Co; 1990;:249-260.
30 +
Fliesler SJ, Anderson RE.  Chemistry and metabolism of lipids in the vertebrate retina.  In: Holman RT, ed. Progress in Lipid Research . London, England: Pergamon Press Ltd; 1983;:79-131.
31 +
Wetzel MD, Fahlman C, Maude MB, et al.  Fatty acid metabolism in normal miniature poodles and those affected with progressive rod-cone degeneration.  In: LaVail MM, Hollyfield JG, Anderson RE, eds. Progress in Clinical and Biological Research: Degenerative Retinal Disorders: Clinical and Laboratory Investigation . New York, NY: Alan R Liss Inc; 1989;:427-439.
32 +
Linton MF, Farese RV Jr, Young SG.  Familial hypobetalipoproteinemia. J Lipid Res . 1993;;34:521-541.
33 +
Malloy MJ, Kane JP, Hardman DA, Hamilton RL, Dalal KB.  Normotriglyceridemic abetalipoproteinemia: absence of the B-100 apolipoprotein. J Clin Invest . 1981;;67:1441-1450.
34 +
Hardman DA, Pullinger CR, Hamilton RL, Kane JP, Malloy MJ.  Molecular and metabolic basis for the metabolic disorder normotriglyceridemic abetalipoproteinemia. J Clin Invest . 1991;;88:1722-1729.
35 +
Roy CC, Levy E, Green PH, et al.  Malabsorption, hypocholesterolemia, and fat-filled enterocytes with increased intestinal apoprotein B chylomicron retention disease. Gastroenterology . 1987;;92:390-399.
36 +
Pessah M, Benlian P, Beucler I, et al.  Andersen's disease: genetic exclusion of the apolipoprotein-B gene in two families. J Clin Invest . 1991;;87: 367-370.
37 +
Bieri JG, Hoeg JM, Schaefer EJ, Zech LA, Brewer HB Jr.  Vitamin A and vitamin E replacement in abetalipoproteinemia. Ann Intern Med . 1984;;100: 238-239.
38 +
Muller DPR.  Effect of large oral doses of vitamin E on the neurological sequelae of patients with abetalipoproteinemia.  In: Lubin B, Machlin LJ, eds. Vitamin E: Biochemical, Hematological and Clinical Aspects . New York, NY: New York Academy of Sciences; 1982;:133-144.
39 +
Runge P, Muller DPR, McAllister J, Calver D, Lloyd JK, Taylor D.  Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinemia. Br J Ophthalmol . 1986;;70:166-173.

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