Question 1 of 10

    Abetalipoproteinemia (Bassen Kornzweig Syndrome)

    Abetalipoproteinemia - very high mag[1]

    Abetalipoproteinemia is a rare autosomal recessive disorder characterized by the inability of the body to absorb lipoproteins from the gastroenterological system due to mutations of proteins responsible for their transport across enterocytes. Diarrhea, failure to thrive, acanthocytosis and central nervous system complications are most important features. The diagnosis requires a thorough diagnostic workup, including laboratory and genetic studies.

    The disease originates from this process: metabolic.

    Presentation

    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].

    Eyes
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  • gastrointestinal
    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]
    • The diarrhea improved with fasting.[journals.lww.com]
    • Peripheral blood acanthocytosis Failure to thrive Atypical retinitis pigmentosa Neuropathy Myopathy Liver: Steatosis, cirrhosis (rare), hepatomegaly Gastrointestinal: Chronic diarrhea (steatorrhea) Ophthalmic Atypical retinitis pigmentosa Anisocoria[basicmedicalkey.com]
    • Children are usually asymptomatic at birth but develop digestive symptoms including diarrhea, steatorrhea and failure to thrive in infancy.[pubmedcentralcanada.ca]
    • Clinically, this disease can cause failure to thrive, diarrhea, fatty stools, and abnormally shaped red blood cells.[sema4genomics.com]
    Chronic Diarrhea
    • diarrhea Peripheral blood acanthocytosis Failure to thrive Atypical retinitis pigmentosa Neuropathy Myopathy Liver: Steatosis, cirrhosis (rare), hepatomegaly Gastrointestinal: Chronic diarrhea (steatorrhea) Ophthalmic Atypical retinitis pigmentosa Anisocoria[basicmedicalkey.com]
    • diarrhea, anemia, FTT Lab Acanthocytosis, VLDL-cholesterol, LDL-cholesterol, absent apoB, when homozygous Management Medium-chain TGs, water-miscible vitamin E a·be·ta·lip·o·pro·tein·e·mi·a ( ā-bā'tă-lip'ō-prō'tē-nē'mē-ă ) A disorder characterized by[medical-dictionary.thefreedictionary.com]
    • One set of features includes signs of fat malabsorption (chronic diarrhea, steatorrhea, and endoscopy of the intestine with what has been described as a "gelee blanche" or "white hoar frosting" appearance (6).[forgottendiseases.org]
    • Case 3 This patient is a five-month-old female who presented to SMC with a history of chronic diarrhea, vomiting and failure to thrive.[omicsonline.org]
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  • neurologic
    Ataxia
    • Providing complementary sections on the anatomy of the spinocerebellar system, its normal function, and a history of ataxia research and management, the Handbook of Ataxia Disorders clarifies the impact of identifying the molecular causes of ataxia offers[books.google.com]
    • 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]
    • 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.[aibolita.com]
    Cerebellar Ataxia
    • Clinical findings Cerebellar ataxia, peripheral neuropathy, retinitis pigmentosa, fat malabsorption, steatorrhoea, chronic diarrhoea, anaemia, failure to thrive.[medical-dictionary.thefreedictionary.com]
    • Movement Disorders cerebellar ataxia: gait disturbances: 33% of patients by 10 years of age 100% of patients by 30 years of age loss of ambulation by 3rd decade dysarthria dysdiadochokinesia dysmetria chorea intention tremors 3.[pedbase.org]
    • . - ME Bouma, I Beucler, LP Aggerbeck - Journal of Clinical , 1986 - ncbi.nlm.nih.gov Cerebellar ataxia - SL Perlman - Current treatment options in neurology, 2000 - Springer Media References Abetalipoproteinemia - very high mag , CC BY-SA 3.0 Languages[symptoma.com]
    Absent Deep Tendon Reflex
    • Neurological problems tend to begin with reduced or absent deep tendon reflexes (e.g. knee jerks) and loss of balance when their eyes are closed (Romberg's sign).[forgottendiseases.org]
    • Neurologic examination may reveal diminished or absent deep tendon reflexes and, less frequently, deficits in proprioception and ataxia.[emedicine.medscape.com]
    • 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[ojrd.biomedcentral.com]
    Absent Knee Reflex
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  • Entire body system
    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]
    • 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[webmd.com]
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  • Workup

    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.

    Laboratory

    Serum
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  • Treatment

    Prognosis

    Complications

    Cerebellar Ataxia
    • Clinical findings Cerebellar ataxia, peripheral neuropathy, retinitis pigmentosa, fat malabsorption, steatorrhoea, chronic diarrhoea, anaemia, failure to thrive.[medical-dictionary.thefreedictionary.com]
    • Movement Disorders cerebellar ataxia: gait disturbances: 33% of patients by 10 years of age 100% of patients by 30 years of age loss of ambulation by 3rd decade dysarthria dysdiadochokinesia dysmetria chorea intention tremors 3.[pedbase.org]
    • . - ME Bouma, I Beucler, LP Aggerbeck - Journal of Clinical , 1986 - ncbi.nlm.nih.gov Cerebellar ataxia - SL Perlman - Current treatment options in neurology, 2000 - Springer Media References Abetalipoproteinemia - very high mag , CC BY-SA 3.0 Languages[symptoma.com]
    Scoliosis
    • Muscle weakness Slurred speech Scoliosis [en.wikipedia.org] Vitamin A Deficiency However, many of the observed effects are due to vitamin E deficiency in particular.[symptoma.com]
    • […] in infancy [3] Steatorrhea /Fatty, pale stools [3] [4] Frothy stools [3] Foul smelling stools [3] Protruding abdomen Intellectual disability / developmental delay Developmental coordination disorder , evident by age ten Muscle weakness Slurred speech Scoliosis[en.wikipedia.org]
    • Other problems in ABL and AVED include high arches, spinal curvature problems such as scoliosis, retinitis pigmentosa, and cardiomyopathy (9).[forgottendiseases.org]
    • On examination, she was a short-statured (height: 143 cm), thin-built (weight: 31 kg) girl with a very low body mass index (BMI: 15.19 kg/m 2 ), dysmorphic facies in the form of prognathism, hypertelorism, malar hypoplasia, and scoliosis.[annalsofian.org]
    Malabsorption Syndrome
    • Lipid buildup in enterocytes reduces their capacity to absorb lipids from ingested food and thus yields a lipid malabsorption syndrome.[pathwaymedicine.org]
    • Prognosis Complications Malabsorption Syndrome Diarrhea and failure to thrive that appears in infancy are strongly suggestive of a malabsorption syndrome .[symptoma.com]
    • Malabsorption Syndrome fat malabsorption: steatorrhea - pale, foul-smelling, bulky stool abdominal distention, vomiting, diarrhea, failure to thrive malabsorption of fat-soluble vitamins - E, A, K - (vitamin D absorption does not appear to be affected[pedbase.org]
    • Patients with ABL usually presented during infancy with history of failure to thrive, severe diarrhea and lipid malabsorption syndrome [ 2 , 5 , 8 ].[omicsonline.org]
    Mental Retardation
    • Others muscle weakness muscle contractions: pes cavus, equinovarus, kyphoscoliosis mental retardation peripheral neuritis 3.[pedbase.org]
    • Diarrhea Reduced growth during infancy Inability to gain weight Bulging of the belly Inadequate growth, even in normal conditions Fatty, foul smelling or bloody stool Delay in mental development/mental retardation Problem with movement or body balance[hxbenefit.com]
    • Retardation Dysequilibrium Syndrom VLDLR Cerebral creatine deficiency syndrome 1 SLC6A8 Cerebrale Cavernome KRIT1, CCM2, PDCD10 Charcot-Marie-Tooth MPZ, GDAP1, GJB1, MFN2, PMP22, NEFL, KIF1B, LMNA, SBF2, HINT1 Charcot-Marie-Tooth Typ1 MPZ, GJB1, PMP22[meduniwien.ac.at]
    Proteinuria
    • It is manifested with corneal opacity, hemolytic anemia, and proteinuria.[icd10data.com]
    Vitamin A Deficiency
    • Neurologic findings in vitamin E deficiency.[annalsofian.org]
    • [www.symptoma.com] Vitamin E Deficiency However, many of the observed effects are due to vitamin E deficiency in particular.[symptoma.com]
    • J.: Increased rate of rapid axonal transport in vitamin E deficient rats.[link.springer.com]
    • "Ataxia with vitamin E deficiency and abetalipoproteinemia".[en.wikipedia.org]
    • Vitamin D deficiency is not consistently described among ABL patients.[ojrd.biomedcentral.com]
    Vitamin E Deficiency
    • Neurologic findings in vitamin E deficiency.[annalsofian.org]
    • J.: Increased rate of rapid axonal transport in vitamin E deficient rats.[link.springer.com]
    • "Ataxia with vitamin E deficiency and abetalipoproteinemia".[en.wikipedia.org]
    • [www.symptoma.com] Vitamin E Deficiency However, many of the observed effects are due to vitamin E deficiency in particular.[symptoma.com]
    • Long-term high dose vitamin E reduced neurological sequelae in other vitamin E-deficient diseases, such as chronic cholestasis [ 19 ], autosomal-recessive vitamin E deficiency (AVED) [ 20 ] and short-bowel syndrome [ 21 ].[ojrd.biomedcentral.com]
    Retinitis Pigmentosa
    • In severe cases, steatorrhea, ataxia, nystagmus, motor incoordination, and retinitis pigmentosa occur.[medical-dictionary.thefreedictionary.com]
    • pigmentosa Neuropathy Myopathy Liver: Steatosis, cirrhosis (rare), hepatomegaly Gastrointestinal: Chronic diarrhea (steatorrhea) Ophthalmic Atypical retinitis pigmentosa Anisocoria Strabismus Xerophthalmia Nyctalopia Ophthalmoplegia Nystagmus Ptosis[basicmedicalkey.com]
    • .: Malformation of the erythrocytes in a case of atypical retinitis pigmentosa.[link.springer.com]
    • The resulting vitamin deficiency can also cause ataxia and retinitis pigmentosa in adulthood.[sema4genomics.com]
    • Affected individuals may also develop degeneration of the retina of the eyes potentially resulting in loss of vision , a condition known as retinitis pigmentosa .[webmd.com]

    Etiology

    Causes

    Malabsorption Syndrome
    • Lipid buildup in enterocytes reduces their capacity to absorb lipids from ingested food and thus yields a lipid malabsorption syndrome.[pathwaymedicine.org]
    • Prognosis Complications Malabsorption Syndrome Diarrhea and failure to thrive that appears in infancy are strongly suggestive of a malabsorption syndrome .[symptoma.com]
    • Malabsorption Syndrome fat malabsorption: steatorrhea - pale, foul-smelling, bulky stool abdominal distention, vomiting, diarrhea, failure to thrive malabsorption of fat-soluble vitamins - E, A, K - (vitamin D absorption does not appear to be affected[pedbase.org]
    • Patients with ABL usually presented during infancy with history of failure to thrive, severe diarrhea and lipid malabsorption syndrome [ 2 , 5 , 8 ].[omicsonline.org]

    Epidemiology

    Sex distribution
    Age distribution

    Pathophysiology

    Prevention

    Summary

    Patient Information

    Self-assessment

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    References

    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.

    • Abetalipoproteinemia [OMIM# 200100] - AJ Larner - 2011 - Springer
    • Cerebellar ataxia - SL Perlman - Current treatment options in neurology, 2000 - Springer
    • Anesthesia for genetic, metabolic, and dysmorphic syndromes of childhood - VC Baum, JE O'Flaherty - 2006 - books.google.com
    • Acanthocytosis Without - EMR Critchley, DB Clark, A Wikler - Archives of Neurology, 1968 - Am Med Assoc
    • Abetalipoproteinemia - D Pautler, D Easley, JF Pohl - Journal of pediatric , 2008 - journals.lww.com
    • Abetalipoproteinemia: two case reports and literature review - R Zamel, R Khan, RL Pollex, RA Hegele - Orphanet J Rare , 2008 - biomedcentral.com
    • Clinical and genetic abnormalities in patients with Friedreich's ataxia - A Dürr, M Cossee, Y Agid, V Campuzano - England Journal of , 1996 - Mass Medical Soc
    • A truncated species of apolipoprotein B (B-38.7) in a patient with homozygous hypobetalipoproteinemia associated with diabetes mellitus - K Ohashi, S Ishibashi, M Yamamoto - , and vascular biology, 1998 - Am Heart Assoc
    • Abetalipoproteinemia presenting as severe vitamin K deficiency - FM Caballero, GR Buchanan - Pediatrics, 1980 - Am Acad Pediatrics
    • Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families - L Cavalier, K Ouahchi, HJ Kayden, S Di Donato - The American Journal of , 1998 - Elsevier
    • A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X–linked retinitis pigmentosa (RP3) - A Meindl, K Dry, K Herrmann, E Manson - Nature , 1996 - nature.com
    • Abetalipoproteinemia and metastatic spinal cord glioblastoma - RP Newman, EJ Schaefer, CB Thomas - Archives of , 1984 - Am Med Assoc
    • With accumulation of an apoprotein B-like protein in intestinal cells. Immunoenzymatic and biochemical characterization of seven cases of Anderson's disease. - ME Bouma, I Beucler, LP Aggerbeck - Journal of Clinical , 1986 - ncbi.nlm.nih.gov
    • AAEM minimonograph# 34: polyneuropathy: classification by nerve conduction studies and electromyography - PD Donofrio, JW Albers - Muscle & nerve, 1990 - Wiley Online Library
    • APPROACH TO A FIVE YEAR OLD WHO PRESENTS WITH ONE MONTH HISTORY OF ATAXIA - M IYPE - NEUROPED 2011 PG TRAINING PROGRAM AND , 2011 - iapkerala.org
    • Abetalipoproteinemia (Bassen-Kornzweig syndrome) - E Kott, G Delpre, U Kadish, M Dziatelovsky - Acta , 1977 - Springer
    • A clinical and neurophysiological investigation of a Danish kindred with heterozygous familial hypobetalipoproteinemia - GE Andersen, W Trojaborg, HC Lou - Acta Paediatrica, 2008 - Wiley Online Library
    • Abetalipoproteinemia in an Indian family - MV Padma, S Jain, MC Maheshwari - Indian journal of pediatrics, 1996 - Springer
    • A possible cause of decreased vision in cryptococcal meningitis - C KUPFER, E McCRANE - Investigative Ophthalmology & Visual Science, 1974 - ARVO
    • A paucity of colonic enteroendocrine and/or enterochromaffin cells characterizes a subset of patients with chronic unexplained diarrhea/malabsorption - S Ohsie, G Gerney, D Gui, D Kahana, MG Martín - Human pathology, 2009 - Elsevier
    • Abetalipoproteinemia: Metabolic, endocrine, and electron-microscopic investigations - MA Sperling, F Hengstenberg, E Yunis, FM Kenny - Pediatrics, 1971 - Am Acad Pediatrics

    Media References

    1. Abetalipoproteinemia - very high mag, CC BY-SA 3.0

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