Abetalipoproteinemia: two case reports and literature review

Abetalipoproteinemia (ABL, OMIM 200100) is a rare, autosomal recessive disorder, characterized by fat malabsorption, acanthocytosis and hypocholesterolemia in infancy. Later in life, deficiency of fat-soluble vitamins is associated with development of atypical retinitis pigmentosa, coagulopathy, posterior column neuropathy and myopathy. ABL results from mutations in the gene encoding the large subunit of microsomal triglyceride transfer protein (MTP; OMIM 157147). To date at least 33 MTP mutations have been identified in 43 ABL patients. We describe the clinical progress of two patients, both currently in the fifth decade of life, who were diagnosed with ABL as children and were treated with high oral doses of fat soluble vitamins, including vitamin E over the last three decades. Treatment appears to have been associated with arrest of the neuropathy and other complications in both patients. Because pharmacologic inhibition of MTP is being developed as a novel approach to reduce plasma cholesterol for prevention of cardiovascular disease, defining the long-term clinical features of patients with a natural deficiency in MTP might provide some insight into the possible effects of such treatments. We review the range of clinical, biochemical and molecular perturbations in ABL.

[1]  T. Schiano,et al.  Efficacy of water-soluble vitamin E in the treatment of vitamin E malabsorption in short-bowel syndrome. , 1994, The American journal of clinical nutrition.

[2]  F A BASSEN,et al.  Malformation of the erythrocytes in a case of atypical retinitis pigmentosa. , 1950, Blood.

[3]  J. Triantafillidis,et al.  Endocrine function in abetalipoproteinemia: a study of a female patient of Greek origin. , 2004, Annali italiani di chirurgia.

[4]  D. Sullivan,et al.  A mild case of abetalipoproteinaemia in association with subclinical hypothyroidism , 2006, Annals of clinical biochemistry.

[5]  D. Muller,et al.  The role of vitamin E in the treatment of the neurological features of abetalipoproteinaemia and other disorders of fat absorption , 1985, Journal of Inherited Metabolic Disease.

[6]  L. Mancano,et al.  Neurologic findings in vitamin E deficiency. , 1997, American family physician.

[7]  D. Rader,et al.  Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia , 1993, Nature.

[8]  D. Rader,et al.  Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. , 1992, Science.

[9]  D. Illingworth,et al.  Abetalipoproteinemia. Report of two cases and review of therapy. , 1980, Archives of neurology.

[10]  H. Mabuchi,et al.  Abetalipoproteinemia caused by maternal isodisomy of chromosome 4q containing an intron 9 splice acceptor mutation in the microsomal triglyceride transfer protein gene. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[11]  I. Sternlieb,et al.  Hepatic peroxisomal abnormalities in abetalipoproteinemia. , 1989, Gastroenterology.

[12]  E. O'Loughlin,et al.  Novel mutations in abetalipoproteinaemia and homozygous familial hypobetalipoproteinaemia , 2007, Journal of Inherited Metabolic Disease.

[13]  P. Barkhaus,et al.  Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis. , 1985, The New England journal of medicine.

[14]  P. Talmud,et al.  The use of a highly informative CA repeat polymorphism within the abetalipoproteinaemia locus (4q22–24) , 1997, Prenatal diagnosis.

[15]  Graeme N. Smith,et al.  Fat-soluble vitamin deficiency in pregnancy: a case report and review of abetalipoproteinemia. , 2006, Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC.

[16]  R. Hegele,et al.  Microsomal triglyceride transfer protein (MTP) gene mutations in Canadian subjects with abetalipoproteinemia , 2000, Human mutation.

[17]  R. Deckelbaum,et al.  Combined vitamin A and E therapy prevents retinal electrophysiological deterioration in abetalipoproteinaemia. , 1982, The British journal of ophthalmology.

[18]  Richard E Gregg,et al.  Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. , 2007, The New England journal of medicine.

[19]  Sturman Rm The Bassen-Kornzweig syndrome: 18 years in evolution. , 1968 .

[20]  J. Lloyd,et al.  EFFECT OF LARGE ORAL DOSES OF VITAMIN E ON THE NEUROLOGICAL SEQUELAE OF PATIENTS WITH ABETALIPOPROTEINEMIA , 1982, Annals of the New York Academy of Sciences.

[21]  Tan Mc,et al.  Neurologic findings in vitamin E deficiency. , 1997 .

[22]  H. Jamil,et al.  A Novel Abetalipoproteinemia Genotype , 1996, The Journal of Biological Chemistry.

[23]  R. Hegele,et al.  Ileal adenocarcinoma in a mild phenotype of abetalipoproteinemia , 2003, Clinical genetics.

[24]  S. Yamashita,et al.  An atypical case of abetalipoproteinaemia with severe fatty liver in the absence of steatorrhoea or acanthocytosis , 2005, European Journal of Pediatrics.

[25]  I. Chowers,et al.  Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipoproteinaemia patients. , 2001, Eye.

[26]  P. Cullen,et al.  Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein. , 1993, Human molecular genetics.

[27]  E. Oldfield,et al.  Abetalipoproteinemia and metastatic spinal cord glioblastoma. , 1984, Archives of neurology.

[28]  M. R. Dische,et al.  The cardiac lesions in Bassen-Kornzweig syndrome. Report of a case, with autopsy findings. , 1970, The American journal of medicine.

[29]  M. Fox,et al.  Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia. , 1995, American journal of human genetics.

[30]  D. Behar,et al.  Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient. , 2007, Molecular genetics and metabolism.

[31]  T. Kanehisa,et al.  Hypobetalipoproteinemia with abnormal prebetalipoprotein , 1977, Journal of the Neurological Sciences.

[32]  D. Illingworth,et al.  Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia. , 2000, Journal of lipid research.

[33]  D. Gambi,et al.  Ataxia with isolated vitamin E deficiency: neurological phenotype, clinical follow-up and novel mutations in TTPAgene in Italian families , 2004, Neurological Sciences.

[34]  Bernard Keavney,et al.  Association of apolipoprotein E genotypes with lipid levels and coronary risk. , 2007, JAMA.

[35]  R. Havel,et al.  Is microsomal triglyceride transfer protein the missing link in abetalipoproteinemia? , 1993, Hepatology.

[36]  L. Sobrevilla,et al.  DEMYELINATING CENTRAL NERVOUS SYSTEM DISEASE, MACULAR ATROPHY AND ACANTHOCYTOSIS (BASSEN-KORNZWEIG SYNDROME). , 1964, The American journal of medicine.

[37]  G. Mentha,et al.  Persistence of the intestinal defect in abetalipoproteinaemia after liver transplantation , 1998, European Journal of Pediatrics.

[38]  D. Muller,et al.  Oral vitamin E supplements can prevent the retinopathy of abetalipoproteinaemia. , 1986, The British journal of ophthalmology.

[39]  I. Chowers,et al.  Long-term assessment of combined vitamin A and E treatment for the prevention of retinal degeneration in abetalipoproteinaemia and hypobetalipo-proteinaemia patients , 2001, Eye.

[40]  S. Bertolini,et al.  Mutations in MTP gene in abeta- and hypobeta-lipoproteinemia. , 2005, Atherosclerosis.

[41]  T. Triche,et al.  Analysis of the apolipoprotein B gene and messenger ribonucleic acid in abetalipoproteinemia. , 1986, The Journal of clinical investigation.

[42]  R. Hegele,et al.  Arrest of neuropathy and myopathy in abetalipoproteinemia with high-dose vitamin E therapy. , 1985, Canadian Medical Association journal.

[43]  H. Gharib,et al.  Hepatic failure with acanthocytosis: association with hemolytic anemia and deficiency of erythrocyte glutathione peroxidase. , 1969, Mayo Clinic proceedings.

[44]  L. Aggerbeck,et al.  The role of the microsomal triglygeride transfer protein in abetalipoproteinemia. , 2000, Annual review of nutrition.