The clinical presentation of abetalipoproteinemia (ABL) stems from an insufficient physiological transport of plasma B-containing lipoproteins - chylomicrons, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), due to mutations of the microsomal triglyceride transfer protein (MTP), responsible for their transfer through enterocytes [1] [2]. Malabsorption of fat and fat-soluble vitamins, principal pathological events, lead to a very early onset of failure to thrive, reduced growth and severe fatty diarrhea (steatorrhea) [1] [3]. Gradually, diarrhea can subside as patients learn to avoid foods that have shown to induce diarrhea, but the deficiency of fat-soluble vitamins can cause numerous symptoms [1] [3]. Central nervous system damage and visual deficits, due to deficiencies of vitamins E and A, respectively, are most important long-term complications. Reduced deep-tendon reflexes, dysmetria, ataxia, diminished proprioception and vibratory sense, as well as progressive neuropathy, may develop in the first two decades of life [1] [4]. Conversely, pigmentary retinopathy leads to scotomas, loss of color and night vision, and even blindness [1] [4]. Additional complications that have been documented in the literature include coagulopathies (due to vitamin K deficiency), myopathy and demyelination that can cause a spastic gait, while reduced fertility is also reported [1] [2] [4].

• Difficulty Walking

  These may include: Sensory disturbances: This includes problems with sensing temperature and touch –– especially in the hands and feet (hypesthesia) Trouble walking (ataxia): Approximately 33 percent of children will have difficulty walking by the time [verywell.com]

  These may include: Sensory disturbances: This includes problems with sensing temperature and touch –– especially in the hands and feet (hypesthesia) Trouble walking ( ataxia ): Approximately 33 percent of children will have difficulty walking by the time [verywellhealth.com]

  Affected individuals experience progressive neurological deterioration, muscle weakness, difficulty walking, and blood abnormalities including a condition in which the red blood cells are malformed (acanthocytosis) resulting in low levels of circulating [rarediseases.org]

• Failure to Thrive

  Malabsorption of fat and fat-soluble vitamins, principal pathological events, lead to a very early onset of failure to thrive, reduced growth and severe fatty diarrhea (steatorrhea). [symptoma.com]

  Clinical manifestations include fat malabsorption and steatorrhea (foul-smelling fatty stools), failure to thrive in children, and deficiencies of fat-soluble vitamins (A, D, E, and K). [pixorize.com]

  Clinical Consequences Abetalipoproteinemia presents in infancy as failure to thrive and steatorrhea. Laboratory Features Nearly undetectable levels of plasma VLDL and LDL. [pathwaymedicine.org]

  […] to thrive, assess malabsorption of fat-soluble vitamins, and the need to change diet Genetic counseling for patients and their first-degree relatives Social worker and nurse to assess the patients for nutritional needs, failure to thrive, and referral [ncbi.nlm.nih.gov]

• Diarrhea

  He improved with good weight gain and resolution of diarrhea on a low-fat diet with fat-soluble vitamin supplementation and parenteral nutrition. [journals.lww.com]

  Gradually, diarrhea can subside as patients learn to avoid foods that have shown to induce diarrhea, but the deficiency of fat-soluble vitamins can cause numerous symptoms. [symptoma.com]

  She reports habitually maintaining a low-fat diet to avoid diarrhea. Blood tests reveal absent LDL cholesterol levels, a prolonged partial thromboplastin time, and low blood tocopherol (vitamin E) levels. [online.epocrates.com]

  Three months later, his fatty diarrhea becomes normal stool, his serum fat-soluble vitamins normalized, and his weight increased from 4.1 kg to 5.9 kg. [ncbi.nlm.nih.gov]

• Chronic Diarrhea

  We investigated three unrelated Tunisian children born from consanguineous marriages, presenting hypobetalipoproteinemia associated with chronic diarrhea and retarded growth. [ncbi.nlm.nih.gov]

  The diagnosis of abetalipoproteinemia was established in the case of a 17-year old man with chronic diarrhea, growth retardation, neurological derangements, visual impairment and retinitis pigmentosa, low plasma cholesterol, triglyceride and LDL cholesterol [turkjem.org]

• Ataxia

  Fredrich Ataxia Autosomal recessive Mutation in the FXN gene leads to triplet repeat expansion. [wikidoc.org]

  Irreversible effects include ataxia, peripheral neuropathy, and retinal degeneration.[6] History and exam Other diagnostic factors age 0 to 12 years steatorrhea/diarrhea low weight muscle weakness muscle contractions loss of deep tendon reflexes ataxia [bestpractice.bmj.com]

  Irreversible effects include ataxia, peripheral neuropathy, and retinal degeneration.[6] Vignette Common Vignette 1 A 4-month-old child presents with faltering growth associated with persistent foul-smelling stools. [online.epocrates.com]

  Clinical findings Cerebellar ataxia, peripheral neuropathy, retinitis pigmentosa, fat malabsorption, steatorrhoea, chronic diarrhoea, anaemia, failure to thrive. [medical-dictionary.thefreedictionary.com]

  [citation needed] Additional complications of the diseases if not properly treated include blindness, mental deterioration, ataxia, loss of peripheral nerve function. [en.wikipedia.org]

• Cerebellar Ataxia

  Clinical findings Cerebellar ataxia, peripheral neuropathy, retinitis pigmentosa, fat malabsorption, steatorrhoea, chronic diarrhoea, anaemia, failure to thrive. [medical-dictionary.thefreedictionary.com]

  Visual, auditory and somatosensory pathway involvement in hereditary cerebellar ataxia, Friedreich’s ataxia and familial spastic paraplegia. Electroencph. clin. Neurophysiol ., 52 : 283 – 297. [cambridge.org]

• Absent Deep Tendon Reflexes

  Neurologic examination may reveal diminished or absent deep tendon reflexes and, less frequently, deficits in proprioception and ataxia. The syndrome is associated with normal longevity. [emedicine.medscape.com]

  Absent or diminished deep tendon reflexes are common to both ABL and the NAs, however, as is liver disease. Refsum disease (RD). RD is a condition that causes problems with myelin in the brain. [forgottendiseases.org]

• Absent Knee Reflex

  Motor exam showed normal tone and power in major muscle groups with absent knee reflexes. The Babinski sign was negative. [ncbi.nlm.nih.gov]

• Areflexia

  Patients develop spinocerebellar ataxia, areflexia, and weakness, accompanying a diffuse neuromuscular disease that resembles Friedreich ataxia. There are crenated or "thorny" red cells on blood smear (acanthocytosis) (Figure 1). [aao.org]

Diarrhea and failure to thrive that appears in infancy are strongly suggestive of a malabsorption syndrome. For this reason, a detailed patient history regarding the onset and course of symptoms is detrimental. In addition, a complete physical examination can detect signs of malnourishment, defects in both lower and upper motor neurons, as well as hepatomegaly and visual deficits, strengthening its equally important role in workup [1]. Laboratory studies will reveal minimal or absent low-density lipoprotein (LDL) and triglycerides, whereas increased liver enzymes (alanine and aspartate aminotransferases, or ALT and AST) due to frequent hepatic steatosis are readily observed [2]. A complete blood count (CBC) with a subsequent peripheral blood smear demarcates the presence of acanthocytes, abnormally shaped cells that comprise up to 50% of visible erythrocytes [1] [2], and their presence is considered a cardinal feature of ABL. Moreover, a profoundly reduced erythrocyte sedimentation rate (ESR), anemia and elevated prothrombin time (PT) are other notable findings, suggesting that a full coagulation panel should be included in initial workup [1]. If clinical and laboratory findings provide sufficient evidence to pursue a diagnosis of ABL, genetic testing must be conducted, even without a positive family history, which is common due to the autosomal recessive pattern of inheritance and frequent absence of symptoms in both parents. Detection of mutations in the MTP protein located on chromosome 4q22-24 will confirm the diagnosis [1]. Hepatomegaly may be seen as a result of steatosis of liver. The biopsy of liver in the diseased patients may reveal steatosis along with the raise in the level of serum transaminase.

• Glycosuria

  Galactose-1-phosphate uridylyltransferase galactosemia, Galactokinase deficiency) - other intestinal carbohydrate absorption (Glucose-galactose malabsorption, Sucrose intolerance) - pyruvate metabolism and gluconeogenesis (PCD, PDHA) - Pentosuria - Renal glycosuria [chemeurope.com]

Lifetime monitorization and symptomatic treatment with fat-soluble vitamins and the implementation of a fat-restrictive diet reduces the morbimortality in affected individuals. [diposit.ub.edu]

See Treatment of Manifestations. Prevention of Secondary Complications See Treatment of Manifestations. [ncbi.nlm.nih.gov]

Treatment Treatment Options: Treatment with vitamins A and E may be beneficial. Cone function improves before rod function with massive doses of vitamin A but usually only after months of treatment. [disorders.eyes.arizona.edu]

Long term treatment and follow-up of ABL The current standard treatment for ABL is dietary modification and replacement of fat soluble vitamins. [ojrd.biomedcentral.com]

Prognosis The prognosis is severe, with a significantly reduced life expectancy. The documents contained in this web site are presented for information purposes only. [orpha.net]

The long-term outlook (prognosis) is reasonably good for most people who are diagnosed and treated early. However, how well each person does depends on the amount of brain and nervous system problems. Therefore, the prognosis can vary. [checkorphan.org]

(Outcomes/Resolutions) The prognosis of Abetalipoproteinemia depends on early recognition and diagnosis of the condition Once a diagnosis of ABL is achieved, then constant surveillance is necessary. [dovemed.com]

You are here Etiology Abetalipoproteinemia is a hereditary deficiency of a protein which transfers lipids to nascent Apolipoprotein B-containing chylomicrons and VLDLs normally synthesized by the small intestine and liver. [pathwaymedicine.org]

Forty-two years after its initial description, a molecular etiology of ABL has been reported to be a deficiency of a microsomal transfer protein, thus suggesting that this protein plays a key role in lipoprotein particle assembly and secretion both in [ncbi.nlm.nih.gov]

Etiology Abetalipoproteinemia is a result of mutations of two alleles of the MTTP gene ( MTP ; 4q24). [orpha.net]

Summary Epidemiology It is very rare, with an estimated prevalence of less than 1/1,000,000. Clinical description ABL/HoFHBL manifests during the first year of life or in young childhood. [orpha.net]

2015 A Compendium of Inherited Disorders and the Eye, Oxford University Press Genetics Also called Bassen-Kornzweig syndrome OMIM Numbers 200100 Inheritance Autosomal recessive Gene/Gene Map Microsomal triglyceride transfer protein deficiency 4q22-q24 Epidemiology [aao.org]

This activity reviews the etiology, epidemiology, pathophysiology, evaluation, and treatment considerations of this disease and highlights the role of the collaboration between interprofessional team members. [ncbi.nlm.nih.gov]

The clinical and pathophysiological features of a case of abetalipoproteinemia in a 34-year-old patient are described. This patient is the first case reported in Japan. [ncbi.nlm.nih.gov]

Abetalipoproteinemia is an inherited metabolic defect that prevents fat-soluble vitamins, such as A and E, from being absorbed from the intestines into the bloodstream and from being secreted by the liver. [clinicaltrials.gov]

Prevention of Primary Manifestations Early treatment with vitamin E (100-300 IU/kg/day) may delay or prevent the development of neurologic dysfunction [Zamel et al 2008]. [ncbi.nlm.nih.gov]

Diet changes are needed to prevent stomach problems. This may involve limiting intake of some types of fat. Supplements of medium-chain triglycerides are taken under the supervision of a health care provider. [mountsinai.org]

Primary Prevention There are no primary preventive measures available for abetalipoproteinemia. [wikidoc.org]

A supplementation to prevent or at least slow the progression of neuromuscular and retinal degenerative disease. [research-repository.uwa.edu.au]

1. Zamel R, Khan R, Pollex RL, Hegele RA. Abetalipoproteinemia: two case reports and literature review. Orphanet Journal of Rare Diseases. 2008;3:19.
2. Ferreira F, Patel V, Matts S. A successful spontaneous pregnancy in abetalipoproteinemia: Amsterdam or the art of vitamin replacement? BMJ Case Rep. 2014;2014:bcr2014206754.
3. Burnett JR, Hooper AJ. Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia. Free Radic Biol Med. 2015;88(Pt A):59-62.
4. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.