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 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  . 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)  . 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  . 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  . Conversely, pigmentary retinopathy leads to scotomas, loss of color and night vision, and even blindness  . 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   .
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]
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]
Zeissig S 1, Dougan SK, Barral DC, Junker Y, Chen Z, Kaser A, Ho M, Mandel H, McIntyre A, Kennedy SM, Painter GF, Veerapen N, Besra GS, Cerundolo V, Yue S, Beladi S, Behar SM, Chen X, Gumperz JE, Breckpot K, Raper A, Baer A, Exley MA, Hegele RA, Cuchel [ncbi.nlm.nih.gov]
- Failure to Thrive
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]
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]
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]
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]
- 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). If ABL is not treated, it progresses and a condition called ataxia develops. [forgottendiseases.org]
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]
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]
- 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]
- Spastic Gait
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. [symptoma.com]
gait • Babinski positive • Severe spasticity by 3rd-4th decades Cerebellar Pathways: • Ataxia • Dysmetria Myopathy: Generalised muscular weakness leads to • kyphoscoiosis, • Lordosis, • pes cavus • untreated: progress to immobility • Complex conduction [pediatriconcall.com]
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 . 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 . 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  , 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 . 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 . 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.
- Zamel R, Khan R, Pollex RL, Hegele RA. Abetalipoproteinemia: two case reports and literature review. Orphanet Journal of Rare Diseases. 2008;3:19.
- 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.
- Burnett JR, Hooper AJ. Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia. Free Radic Biol Med. 2015;88(Pt A):59-62.
- 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.