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]

• Cerebral Palsy

  • Epsom Salt Cut Cerebral Palsy Rate in Half Among Preemies - Jan 31, 2008, 12:00 Researchers note most hospitals already stocked with simple, inexpensive solution. • Atkins-Like Diet Cuts Epileptic Seizures - Jan 31, 2008, 12:00 High-fat, low-carb [web.archive.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]

  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]

  C, who presented with failure to thrive due to steatorrhea. A four-month-old Sri Lankan girl presented to our pediatric service for evaluation of failure to thrive, having been exclusively breastfed. [rarediseasesjournal.com]

  Typically, patients present with failure to thrive, acanthocytosis, pigmented retinopathy and neurological features. It has been shown that ABL results from mutations in the gene encoding the microsomal triglyceride transfer protein (MTTP). [ncbi.nlm.nih.gov]

• Diarrhea

  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]

  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]

  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]

• 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]

• Scleral Icterus

  She had mild bilateral scleral icterus. Cranial nerve exam was normal apart from decreased visual acuity on the right side. The gait was wide-based. Romberg test was positive but she had no dysmetria and no dysdiadochokinesia. [ncbi.nlm.nih.gov]

• Proximal Muscle Weakness

  Neurological examination revealed mild dysarthria, reduced muscle bulk, bilateral proximal muscle weakness, absent deep-tendon reflexes, upgoing plantar reflexes, reduced sensitivity to light touch with loss of proprioception and vibration sense in a [ncbi.nlm.nih.gov]

• Oligomenorrhea

  She also had a long history of oligomenorrhea. Subjectively, her symptoms had otherwise remained stable for decades. Her parents were first cousins. Her family history included two sisters with Alport syndrome. There was no family history of ABL. [ncbi.nlm.nih.gov]

• Ataxia

  Cerebellar atrophy was negative on neuroimaging; the differential diagnosis to be considered in early onset ataxia without cerebellar atrophy include Friedrich ataxia, ataxia with vitamin-E deficiency, Refsum disease, glucose transporter 1 deficiency, [annalsofian.org]

  The resulting disease causes muscle weakness, ataxia, cardiac hypertrophy, deafness, and retinal degeneration. Contact Category: Eye diseases [aibolita.com]

  In severe cases, steatorrhea, ataxia, nystagmus, motor incoordination, and retinitis pigmentosa occur. [medical-dictionary.thefreedictionary.com]

  The good outcome of the early-treated patients contrasts with severe ataxia and retinopathy observed in the patient with delayed treatment. [ncbi.nlm.nih.gov]

• Absent Deep Tendon Reflexes

  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]

  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.com]

  However, deep-tendon reflexes remained absent and plantar reflexes were still upgoing. Light touch, vibration and proprioreception deficient and bilateral dysmetria persisted, but had not progressed. [ncbi.nlm.nih.gov]

• 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]

  Familial hypobetalipoproteinaemia complicated by cerebellar ataxia and steatocystoma multiplex. J Intern Med. 1991 Feb. 229(2):197-9. [Medline]. Bednarska-Makaruk M, Bisko M, Pulawska MF, Hoffman-Zacharska D, Rodo M, Roszczynko M, et al. [emedicine.medscape.com]

• 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]

• Positive Romberg Sign

  Romberg sign [ 8 ]. [ncbi.nlm.nih.gov]

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.

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

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]

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]

In 183 short chapters, the book provides the essentials clinicians need on symptoms/signs, diagnostic tests, and neurologic disorders of all etiologies. For this edition, Timothy A. [books.google.ro]

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]

These findings are difficult to interpret because of severe caudate atrophy, concurrent medications, and small sample sizes. [23] Epidemiology Frequency United States Neuroacanthocytosis is a rare disease for which insufficient epidemiological data are [emedicine.medscape.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]

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 primary pathophysiology is demyelination due to deficiency of lipid-soluble vitamins. The central and peripheral nervous systems are both affected. [statpearls.com]

The 32 cases, carefully selected to cover common diseases and important principles, are supplemented by clinical descriptions of each disease and a comprehensive discussion of the underlying pathophysiological mechanisms and associated enzymatic and chemical [books.google.com]

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

Treatment with vitamin E is effective in managing the neuropathy if instituted early, but the retinopathy may not be reversible or preventable. [mayoclinic.pure.elsevier.com]

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]

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.