The cases of two sisters with abetalipoproteinemia are reported. Both presented the complete clinical and biological features of the disease: ataxia, retinitis pigmentosa, lack of apolipoprotein B, chylomicrons, LDL and VLDL, reduced titers of serum cholesterol and triglycerides, acanthocytosis, very low levels of serum vitamin A and E. Abetalipoproteinemia is a rare autosomal inherited disease. It is usually revealed during early childhood by steatorrhea and failure to thrive; ataxia and retinitis pigmentosa appear later. The originality of these two cases stems from: 1) their late and fortuitous diagnosis: the first sister was investigated at the age of 42 after the discovery of a vitamin K induced coagulation disorder. The other sister was 39 when she was routinely examined as a family member; 2) the presence of constipation without any other suggestive digestive complaint. However, white discoloration of the duodenal mucosa seen at endoscopy and lipid droplets within the intestinal absorptive cells at biopsy were characteristic. Barium studies showed diffuse involvement of the small bowel which was displaced by an enlarged sigmoid. Treatment consists of administration of vitamin A and vitamin E which prevent or delay ocular and neurologic symptoms. Vitamin K is associated whenever necessary.

Fat-soluble vitamins are normally absorbed from the diet through the gastrointestinal tract and incorporated into fat-rich particles called chylomicrons made in the intestinal wall. Chylomicrons are secreted by the intestine into the bloodstream. In a rare lipid metabolic disorder called abetalipoproteinemia, a defect in the assembly of the fat and vitamin containing particles prevents the formation of chylomicrons resulting in the malabsorption of fat and fat-soluble vitamins. A similar assembly defect of fat and fat-soluble vitamins occurs in the liver and prevents the secretion of these particles. Severe fat-soluble vitamin deficiency results even despite mega doses of oral fat-soluble vitamins. Clinically, the subjects develop neurologic and ophthalmologic symptoms similar to those in Vitamin A and E deficiency. This study is designed to determine whether short-term intravenous fat-soluble vitamins and fat emulsion can reverse the neurologic and ophthalmologic complications of fat-soluble vitamin deficiency based on noninvasive procedures routinely employed in clinical practice.

A 26-year old male suffered from Abeta-lipoproteinemia (Bassen-Kornzweig disease). In addition to C.N.S. lesions, he had myopathy. A muscle biopsy revealed accumulation of ceroid pigment in the striated muscle. A few muscle fibers showed severe degeneration of the myofibrils. Fibroblasts and macrophages in the interstitial tissue contained abundant ceroid. The relation between ceroid accumulation, abetalipoproteinemia and vitamin E-deficiency is discussed.

OBJECTIVE: Description of rickets as an unexpected initial manifestation in two children with abetalipoproteinemia and hypobetalipoproteinemia, and elucidation of its pathophysiology in these conditions. METHODOLOGY: Two infants aged two and six months with abetalipoproteinemia and hypobetalipoproteinemia respectively had clinical rickets at presentation, confirmed radiologically and biochemically. Vitamin D intake and serum levels were measured and other causes of rickets were looked for. RESULTS: Vitamin D intake and laboratory studies levels were suggestive of rickets due to calcium deficiency instead of vitamin D deficiency. Healing of rickets occurred with dietary treatment of the malabsorption, without any dietary calcium or significant vitamin D supplementation. CONCLUSION: Steatorrhea-induced calcium malabsorption seems to be the most likely cause of rickets in this entity.

We report a probable case of abetalipoproteinemia in an infant who presented with unusual symptoms of late-onset vitamin K deficiency. Abetalipoproteinemia is a rare autosomal recessive disease caused by mutation of the microsomal triglyceride transfer protein gene, resulting in the absence of microsomal triglyceride transfer protein function in the small bowel. It is characterized by the absence of plasma apolipoprotein B-containing lipoproteins, fat malabsorption, hypocholesterolemia, retinitis pigmentosa, progressive neuropathy, myopathy, and acanthocytosis. A biopsy of the small intestine characteristically shows marked lipid accumulation in the villi of enterocytes. Large supplements of fat-soluble vitamins A, D, E, and K have been shown to limit neurologic and ocular manifestations. Dietary fat intake is limited to medium-chain triglycerides.

AIM: To investigate the pituary, genitalia, adrenal, thyroid, parathyroid and pancreatic endocrine function of a female patient aged 37 with abetalipoproteinemia at the time of diagnosis and 5 years thereafter (after application of a modified diet). SUBJECT-METHODS: Serum concentrations of cortisol, A4, ACTH, aldosteron, renin, dehydroepiandrosterone sulfate (DHEA-5), progesterone, 17-OH progesterone, testosterone, SH13G, estradiol, luteinizing hormone, follicle stimulating hormone, T3, T4, TSH, FT3, FT4, parathormone, osteocalcin, prolactin, proinsuline, insulin, glucagon, somatomedin-C (Insulin-like Growth Factor-1, IGF-1), IG171-13P3, 25 (OH) Vitamin D3 and 1-25 (OH) 2 Vitamin D3, were measured by radioimmunoassay. Synactlien test, and 24-hour urine cortisol, were also estimated. Serum leptin estimation was carried-out using a sensitive enzymatic technique. Ionized part of serum calcium was measured by the use of a special machine (CORNING), while bone alkaline phosphatase was measured by radioimmunoassay. RESULTS: Serum progesterone and 17-OH-progesterone were reduced in both examinations. Estimation of serum progesterone performed on the 21th day of the menstrual cycle revealed again values below the lowest normal limit. Serum prolactin was increased both in rest and during movement. The levels of both, somatomedin-C (IGF-1) and leptin were below the lowest normal limit. Despite normal serum parathormone, serum-ionized calcium and 25-OH vitamin D were low, while serum bone alkaline phosphatase was increased. Serum proinsulin was increased, and serum insulin was low. Serum thyroid hormone, glucagon, parathormone, FSH, LH, ACTH, testosterone, estradiol and SH13G were normal. The hormonal profile of the patient estimated 5 years later did not differ substantially suggesting that the metabolic improvement due to the adoption of the modified diet had not any significant impact on it. CONCLUSION: Female patients with abetalipoproteinernia have reduced production of progesterone by the corpus luteum and slightly abnormal bone metabolism. The reduced production of progesterone is probably due to the low levels of serum LDL and cholesterol, while reduced serum levels of Leptin and IG17-1 are probably due to the impairment nutritional status. The adoption of a modified diet does not alter the hormonal profile significantly.

A case of oxalate lithiasis associated with Abetalipoproteinemia is reported. The excessive absorption of dietary oxalate in this patient with fat malabsorption occurs because unabsorbed fatty acids in the bowel lumen combine with calcium ions which would otherwise impair oxalate absorption by forming insoluble calcium oxalate crystals. The medical management include dietary fat restriction and supplements of the fat soluble vitamins A, E and K. The prognostic is poor particularly in the neurological and retinal component of this disease.

BACKGROUND: Abetalipoproteinemia is a rare disorder of fat absorption, characterized by vitamin deficiency, acanthocytosis, and neurologic symptoms including ataxia and tremor. CASE REPORT: A 41-year-old male with abetalipoproteinemia is presented. He underwent staged bilateral thalamic deep brain stimulation (DBS) for the treatment of his tremors. After DBS, the patient achieved significant improvements in his tremors, ataxia, and quality of life. DISCUSSION: Thalamic DBS proved to be both safe and efficacious in the management of ataxia and tremors in a patient with abetalipoproteinemia. This is the first report of DBS in abetalipoproteinemia in the literature.

Abetalipoproteinaemia (ABL) is an autosomal recessive disorder characterized by very low plasma concentrations of total cholesterol and triglyceride (TG). It results from mutations in the gene encoding microsomal TG transfer protein (MTTP). A nine-month-old girl was admitted to hospital because of fever, cough, diarrhea and failure to thrive. She had low cholesterol and TG levels according to her age. The peripheral blood smear revealed acanthocytosis. Thyroid function test showed central hypothyroidism. Cranial magnetic resonance imaging revealed the retardation of myelination and pituitary gland height was 1.7 mm. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene. Vitamins A, D, E, and K and levothyroxine were started. The coexistence of ABL and central hypothyroidism has not previously been reported. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene.

Abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD) are extremely rare recessive forms of hypobetalipoproteinemia characterized by intestinal lipid malabsorption and severe vitamin E deficiency. Vitamin E is often supplemented in the form of fat-soluble vitamin E acetate, but fat malabsorption considerably limits correction of the deficiency. In this crossover study, we administered two different forms of vitamin E, tocofersolan (a water-soluble derivative of RRR-α-tocopherol) and α-tocopherol acetate, to three patients with ABL and four patients with CMRD. The aims of this study were to evaluate the intestinal absorption characteristics of tocofersolan versus α-tocopherol acetate by measuring the plasma concentrations of α-tocopherol over time after a single oral load and to compare efficacy by evaluating the ability of each formulation to restore vitamin E storage after 4 months of treatment. In patients with ABL, tocofersolan and α-tocopherol acetate bioavailabilities were extremely low (2.8% and 3.1%, respectively). In contrast, bioavailabilities were higher in patients with CMRD (tocofersolan, 24.7%; α-tocopherol acetate, 11.4%). Plasma concentrations of α-tocopherol at 4 months were not significantly different by formulation type in ABL or CMRD. This study provides new insights about vitamin E status in ABL and CMRD and suggests the potential of different formulations as treatment options.