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 [verywellhealth.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 [verywell.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]

  […] to thrive, diarrhea, steatorrhea Laboratory Lipid profile shows no chylomicrons, no VLDL, no LDL CBC smear shows acantholytic red blood cells (burr cells) due to lipid membrane abnormalities Microscopic (histologic) description Marked fat vacuoles in [pathologyoutlines.com]

  It results in fatty stools, diarrhea, failure to thrive in infancy, and problems with nerves. [medical-dictionary-search-engines.com]

  Symptoms include: Balance and coordination difficulties Curvature of spine Decreased vision that gets worse over time Developmental delay Failure to thrive (grow) in infancy Muscle weakness Poor muscle coordination that usually develops after age 10 Protruding [medlineplus.gov]

  ABL presents early in life with the gastroenterological manifestations of fat malabsorption, steatorrhea, and failure to thrive, and later in life, with progressive ophthalmopathy and neuropathy as a result of deficiency of the fat-soluble vitamins A [research-repository.uwa.edu.au]

• Diarrhea

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

  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]

  A 13-month-old Filipino boy presented with an 11-month history of emesis, diarrhea, hepatomegaly, wasted extremities, and growth failure. The diarrhea improved with fasting. [journals.lww.com]

  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]

• 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]

• Abdominal Distension

  distension) and eventual wasting, which often present by infancy or childhood.[2][4] Fats, cholesterol, and fat-soluble vitamins such as A, D, E, and K are poorly absorbed, leading to dietary deficiency.[1][2][5][6] If discovered early and treated, nutrition [bestpractice.bmj.com]

  Steatorrhea with abdominal distension, failure to thrive, malnutrition, and spinal curvature beginning in the first few months of life are all present. [aao.org]

  It usually presents in infants as failure to thrive, steatorrhea, and abdominal distension and results in spinocerebellar degeneration and retinitis pigmentosa.[3] Epidemiology Abetalipoproteinemia occurs in less than 1 in 1 million persons. [ncbi.nlm.nih.gov]

• Night Blindness

  blindness poor eyesight ophthalmoplegia fatigue pale skin optic disc swelling hepatomegaly Other diagnostic factors Risk factors genetic consanguineous parents More risk factors Diagnostic investigations 1st investigations to order fasting lipid panel [bestpractice.bmj.com]

  Abstract Two siblings presenting with short stature and severely retarded skeletal maturation were found to have steatorrhea, retinitis pigmentosa, night blindness, and loss of posterior column function. [pediatrics.aappublications.org]

  The patient notes night blindness and, if the condition is untreated, eventually demonstrates loss of foveal function and diffuse drusenlike spots similar to those in retinitis punctata albescens. [aao.org]

• Strabismus

  People with abetalipoproteinemia may also have other eye problems, including involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and weakness of the external muscles of the eye (ophthalmoplegia). [ghr.nlm.nih.gov]

  Ptosis, ophthalmoplegia, strabismus, and nystagmus are less common findings. Therapeutic Aspects Serum vitamin A levels should be determined. [aao.org]

• Blepharoptosis

  Cystic Lesions Entropion and Ectropion Eyelashes and Eyebrows Postoperative Cases and Surgical Procedures Ptosis(Blepharoptosis) and Retraction Systemic Diseases Trauma (Injury) Tumors, Neoplasma Neuro-Ophthalmology Optic Nerve Orbit Retina Sclera Strabismus [atlasophthalmology.net]

• Ataxia

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

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

• Nystagmus

  People with abetalipoproteinemia may also have other eye problems, including involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and weakness of the external muscles of the eye (ophthalmoplegia). [ghr.nlm.nih.gov]

  Ptosis, ophthalmoplegia, strabismus, and nystagmus are less common findings. Therapeutic Aspects Serum vitamin A levels should be determined. [aao.org]

  Neurological Involvement Peripheral neuropathy, delayed intellectual development, tremor, nystagmus, loss of deep tendon reflexes These may be myriad and variable in their severity. [statpearls.com]

• Dysmetria

  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. [symptoma.com]

  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 dysmetria [bestpractice.bmj.com]

  If left untreated, the disease progresses to spinocerebellar ataxia (fasciculi cuneatus and gracilis), dysmetria, loss of proprioception and deep tendon reflexes, peripheral neuropathy, ... [accessanesthesiology.mhmedical.com]

  Movement disorders: Tremors, shaking (chorea), trouble reaching for things (dysmetria), trouble talking (dysarthria) Muscle problems: Weakness, shortening (contraction) of muscles in the back that causes the spine to curve (kyphoscoliosis) Blood problems [verywellhealth.com]

  Quick Reference Key Factors Other Factors age 0 to 12 years steatorrhea/diarrhea low weight muscle weakness muscle contractions loss of deep tendon reflexes ataxia dysmetria dysarthria night blindness poor eyesight ophthalmoplegia fatigue pale skin optic [online.epocrates.com]

• 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]

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.

Treatment Treatment involves large doses of vitamin supplements containing fat-soluble vitamins ( vitamin A, vitamin D, vitamin E, and vitamin K ). Linoleic acid supplements are also recommended. [leehealth.org]

Follow-up includes monitoring for ophthalmologic, neurologic, hematologic, and hepatic complications, as well as compliance with treatment. [ncbi.nlm.nih.gov]

Treatment: The recommended treatments for ABL include diet restrictions and vitamin supplementation. Reduced triglyceride content in the diet is suggested if intestinal symptoms require it. [medigoo.com]

Additional treatment is symptomatic and supportive. [rarediseases.org]

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]

Prognosis is variable, but early diagnosis and strict adherence to treatment can recover normal neurological function and halt disease progression. [ncbi.nlm.nih.gov]

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]

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

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]

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]

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]

Molecular and Systemic Pathophysiology The microsomal triglyceride transfer protein (MTP) is required for the assembly and secretion of apoB containing lipoproteins in the liver and intestine [ 3 ]. [link.springer.com]

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]

Abstract 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. [jstage.jst.go.jp]

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]

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

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. [leehealth.org]

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.