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.


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
  • more...
  • gastrointestinal
    Diarrhea
    • 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]
    • 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]
    • Clinically, this disease can cause failure to thrive, diarrhea, fatty stools, and abnormally shaped red blood cells. The resulting vitamin deficiency can also cause ataxia and retinitis pigmentosa in adulthood.[sema4genomics.com]
    • […] related to the malabsorption of fat … —Hélène Puccio and Michel Koenig, in Neurodegenerative Diseases: Neurobiology, Pathogenesis, and Therapeutics , 2005 — called also Bassen-Kornzweig syndrome Note: Common symptoms of abetalipoproteinemia include diarrhea[merriam-webster.com]
    • […] synthesis and export of apoprotein B from intestinal mucosal cells As a result, free fatty acids and monoglycerides cannot be assembled into chylomicrons and become triglycerides stored within cells, causing lipid vacuolization Symptoms: failure to thrive, diarrhea[pathologyoutlines.com]
    Chronic Diarrhea
    • 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]
    • 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. The diarrhea and vomiting started at the age of ten days while weight loss was noticed at the age of two months.[omicsonline.org]
  • more...
  • 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]
    • 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. скачать dle 12.1 Contact Category: Eye diseases[aibolita.com]
    • Coverage includes separate chapters on autism, autosomal recessive ataxias, and autosomal dominant ataxias, and new chapters on endovascular neuroradiology, parkinsonian syndromes, Lewy body dementias, frontotemporal dementia, vanishing white matter,[books.google.com]
    Absent Deep Tendon Reflex
    • 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]
    • 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]
    Cerebellar Ataxia
    Absent Knee Reflex
    • Motor exam showed normal tone and power in major muscle groups with absent knee reflexes. The Babinski sign was negative.[ojrd.biomedcentral.com]
  • more...
  • Entire body system
    Difficulty Walking
    • 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]
    • 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]
  • more...
  • 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
  • more...
  • Treatment

    Prognosis

    Complications

    Cerebellar Ataxia
    Scoliosis
    • […] 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]
    • 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]
    • 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.[symptoma.com]
    • Patients with ABL usually presented during infancy with history of failure to thrive, severe diarrhea and lipid malabsorption syndrome [ 2 , 5 , 8 ]. They exhibit symptoms of intestinal lipid malabsorption and low plasma lipid levels [ 1 , 5 , 6 ].[omicsonline.org]
    Mental Retardation
    • 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
    • Disease characterized by abnormally low levels of plasma lecithin cholesterol acyl transferase; clinical manifestations include corneal opacity, anemia, and proteinuria.[icd10data.com]
    Vitamin A Deficiency
    • Until date, this has been reported in patients with vitamin-E deficiency due to other causes, [8] but not in patients with abetalipoproteinemia. Vitamin-E deficiency can also cause myopathy and neuropathy.[annalsofian.org]
    • The relation between ceroid accumulation, abetalipoproteinemia and vitamin E-deficiency is discussed.[link.springer.com]
    • Many of the signs and symptoms of abetalipoproteinemia result from a severe vitamin deficiency, especially vitamin E deficiency, which typically results in eye problems with degeneration of the spinocerebellar and dorsal column tracts.[en.wikipedia.org]
    • Vitamin D deficiency is not consistently described among ABL patients.[ojrd.biomedcentral.com]
    • Nervous system : Vitamin E deficiency leads to demyelination, hyporeflexia, decreased proprioception & vibration sense and ataxia. Muscles : Myopathy, weakness. Eyes : Retinitis Pigmentosa, blindness in later stages (if untreated).[genetics4medics.com]
    Vitamin E Deficiency
    • Until date, this has been reported in patients with vitamin-E deficiency due to other causes, [8] but not in patients with abetalipoproteinemia. Vitamin-E deficiency can also cause myopathy and neuropathy.[annalsofian.org]
    • The relation between ceroid accumulation, abetalipoproteinemia and vitamin E-deficiency is discussed.[link.springer.com]
    • "Ataxia with vitamin E deficiency and abetalipoproteinemia". Handbook of clinical neurology . Handbook of Clinical Neurology. 103 : 295–305. doi : 10.1016/B978-0-444-51892-7.00018-8 . ISBN 9780444518927 . PMID 21827896 .[en.wikipedia.org]
    • Nervous system : Vitamin E deficiency leads to demyelination, hyporeflexia, decreased proprioception & vibration sense and ataxia. Muscles : Myopathy, weakness. Eyes : Retinitis Pigmentosa, blindness in later stages (if untreated).[genetics4medics.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]
    • .: Malformation of the erythrocytes in a case of atypical retinitis pigmentosa.[link.springer.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]
    • The resulting vitamin deficiency can also cause ataxia and retinitis pigmentosa in adulthood. Without treatments, life expectancy is significantly reduced, but with medical management patients may have a near-normal lifespan.[sema4genomics.com]
    • In individuals with abetalipoproteinemia , the retinitis pigmentosa can result in complete vision loss.[ghr.nlm.nih.gov]

    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]
    • 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.[symptoma.com]
    • Patients with ABL usually presented during infancy with history of failure to thrive, severe diarrhea and lipid malabsorption syndrome [ 2 , 5 , 8 ]. They exhibit symptoms of intestinal lipid malabsorption and low plasma lipid levels [ 1 , 5 , 6 ].[omicsonline.org]

    Epidemiology

    Sex distribution
    Age distribution

    Pathophysiology

    Prevention

    Summary

    Patient Information

    Self-assessment

    Ask Question


    5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.

    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.

    1. Abetalipoproteinemia [OMIM# 200100] - AJ Larner - 2011 - Springer
    2. Cerebellar ataxia - SL Perlman - Current treatment options in neurology, 2000 - Springer
    3. Anesthesia for genetic, metabolic, and dysmorphic syndromes of childhood - VC Baum, JE O'Flaherty - 2006 - books.google.com
    4. Acanthocytosis Without - EMR Critchley, DB Clark, A Wikler - Archives of Neurology, 1968 - Am Med Assoc
    5. Abetalipoproteinemia - D Pautler, D Easley, JF Pohl - Journal of pediatric , 2008 - journals.lww.com
    6. Abetalipoproteinemia: two case reports and literature review - R Zamel, R Khan, RL Pollex, RA Hegele - Orphanet J Rare , 2008 - biomedcentral.com
    7. [Eye movement abnormalities as a sign for the diagnosis in Niemann-Pick disease type C] - D Lengyel, M Weissert, L Schmid - Klinische Monatsblatter fur , 1999 - ukpmc.ac.uk
    8. 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
    9. Abetalipoproteinemia presenting as severe vitamin K deficiency - FM Caballero, GR Buchanan - Pediatrics, 1980 - Am Acad Pediatrics
    10. 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
    11. 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
    12. Abetalipoproteinemia and metastatic spinal cord glioblastoma - RP Newman, EJ Schaefer, CB Thomas - Archives of , 1984 - Am Med Assoc
    13. [alpha] 1-Antitrypsin Deficiency: From Genotype to Childhood Disease - N Marcus, JH Teckman - Journal of pediatric , 1998 - journals.lww.com
    14. AAEM minimonograph# 34: polyneuropathy: classification by nerve conduction studies and electromyography - PD Donofrio, JW Albers - Muscle & nerve, 1990 - Wiley Online Library
    15. 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
    16. Abetalipoproteinemia (Bassen-Kornzweig syndrome) - E Kott, G Delpre, U Kadish, M Dziatelovsky - Acta , 1977 - Springer
    17. 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
    18. Abetalipoproteinemia in an Indian family - MV Padma, S Jain, MC Maheshwari - Indian journal of pediatrics, 1996 - Springer
    19. A possible cause of decreased vision in cryptococcal meningitis - C KUPFER, E McCRANE - Investigative Ophthalmology & Visual Science, 1974 - ARVO
    20. 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
    21. 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

    Languages