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].

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.

The primary treatment for abetalipoproteinemia focuses on dietary management and supplementation. Patients are advised to follow a low-fat diet and take high doses of fat-soluble vitamins to address deficiencies. Vitamin E supplementation is particularly important to prevent neurological damage. Medium-chain triglycerides (MCTs) can be included in the diet as they are more easily absorbed. Regular monitoring by a multidisciplinary team, including a dietitian and neurologist, is essential to manage symptoms and prevent complications.

The prognosis for individuals with abetalipoproteinemia varies depending on the severity of the condition and the effectiveness of treatment. Early diagnosis and appropriate management can significantly improve quality of life and reduce the risk of complications. However, some neurological and visual impairments may be irreversible if not addressed promptly. Lifelong adherence to dietary modifications and vitamin supplementation is crucial for maintaining health and preventing disease progression.

Abetalipoproteinemia is caused by mutations in the MTTP gene, which encodes the microsomal triglyceride transfer protein. This protein is essential for the assembly and secretion of apolipoprotein B-containing lipoproteins. The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to develop the disease. Carriers, who have only one copy of the mutation, typically do not exhibit symptoms.

Abetalipoproteinemia is an extremely rare disorder, with only a few hundred cases reported worldwide. It affects both males and females equally and is found in various ethnic groups. Due to its rarity, the exact prevalence is not well established, but it is considered a very uncommon genetic condition.

The pathophysiology of abetalipoproteinemia involves the disruption of lipid transport and metabolism. The absence of functional microsomal triglyceride transfer protein impairs the formation of chylomicrons and very low-density lipoproteins (VLDL), which are necessary for the transport of dietary fats and fat-soluble vitamins from the intestines to the bloodstream. This leads to fat malabsorption, resulting in nutritional deficiencies and the accumulation of unabsorbed fats in the intestines. The lack of essential vitamins and nutrients contributes to the neurological, muscular, and ocular symptoms observed in affected individuals.

Currently, there is no known way to prevent abetalipoproteinemia, as it is a genetic disorder. However, genetic counseling can be beneficial for families with a history of the condition. Prospective parents who are known carriers of the MTTP gene mutation may consider genetic testing and counseling to understand the risks of passing the condition to their offspring.

Abetalipoproteinemia is a rare genetic disorder characterized by the inability to properly absorb and transport dietary fats and fat-soluble vitamins. It leads to a range of symptoms, including growth failure, neurological issues, and vision problems. Diagnosis involves clinical evaluation, laboratory tests, and genetic analysis. Treatment focuses on dietary management and vitamin supplementation to address deficiencies and prevent complications. While the condition is lifelong, early intervention can improve outcomes and quality of life.

If you or a loved one has been diagnosed with abetalipoproteinemia, it's important to understand the nature of the condition and the steps you can take to manage it. This genetic disorder affects the body's ability to absorb fats and certain vitamins, leading to various health issues. Working closely with healthcare providers, including a dietitian, can help you develop a tailored dietary plan that includes necessary vitamin supplements. Regular follow-ups and monitoring are crucial to ensure optimal health and prevent complications. Remember, while abetalipoproteinemia is a lifelong condition, with proper management, individuals can lead fulfilling lives.

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.