Introduction

Abetalipoproteinemia (ABL) is a seldom-seen autosomal recessive condition characterised by decreased or non-existent quantities of plasma cholesterol, low-density lipoproteins (LDLs), and very-low-density lipoproteins (VLDLs). It should not be mistaken for a lack of beta-lipoproteins. Key symptoms include difficulty absorbing fats, degeneration of the spinal cord and cerebellum, abnormally shaped red blood cells, and inflammation of the retina. 

Microsomal Triglyceride Transfer protein (MTP) serves as a chaperone to transfer lipids onto apolipoprotein B (apo B), situated in the microsomes of the liver and intestinal mucosa to aid in the movement of various lipids between membranes. The rates of lipid transport decrease in the sequence from triglyceride to cholesteryl ester to diglyceride to cholesterol to phosphatidylcholine. MTP, unlike other lipid transfer proteins, consists of subunits with molecular masses of 58 and 97 kDa, forming a heterodimer. The lipid transfer activity is present in the 97-kDa subunit or is given to the complex by it. Abetalipoproteinemia may lack the large subunit of MTP.

In the endoplasmic reticulum, the initial step of assembly occurs and involves the formation of apolipoproteins, cholesterol, phospholipid, and triacylglycerides within lipoprotein particles. While apoB-48 lacks it, apoB-100 includes the necessary binding site for hepatocyte LDL receptor uptake of LDL. ApoB-48 originates from the same gene as apoB-100 and is transported by CMs.¹

Overview of clinical manifestations

Neurological symptoms

• Loss of night and/or colour vision
• Acquired atypical pigmentation of the retina
• Spinocerebellar ataxia and myopathy

Gastrointestinal symptoms

• Failure to thrive, with diarrhoea and vomiting
• Fat malabsorption with steatorrhea (excessive fat in your faeces)
• Hepatomegaly (enlarged liver)²

Skeletal and growth-related abnormalities

Short stature and severely retarded skeletal maturation were found to be related to ABL.³

Skeletal abnormalities

Osteopenia

Osteopenia is a term used in the medical field to indicate a reduction in bone mineral density (BMD) that is lower than normal levels, but not severe enough to be classified as osteoporosis. BMD is detected through DXA bone scans and can also be attributed to secondary causes. Medical issues encompass hyperparathyroidism, anorexia, malabsorption syndromes, hyperthyroidism, chronic kidney disease, hypogonadism, amenorrhea/oligomenorrhea, early menopause, and chronic health problems causing calcium and/or vitamin D deficiencies. Medications linked to the development of the disease include high levels of glucocorticoids/extended use of steroids, valproic acid, proton pump inhibitors, antiepileptic drugs, and chemotherapy medications.⁴

Osteoporosis

Osteoporosis is defined by low bone mass, poor bone quality, and a higher risk of fractures. It is now considered a major issue of the skeletal system due to major metabolic shifts affecting not just bones, but also overall body balance. The development of osteoporosis involves various factors and is difficult to pinpoint. Changes in bone density can indicate the ultimate route through which disease-causing factors impact the likelihood of experiencing a fracture due to osteoporosis in the future. Understanding how different physiological processes work together to achieve peak bone mass and maintain adult bone mass is crucial in grasping the development of this illness.⁵

Rickets-like symptoms

Rickets is a condition that affects the development of children's bones, resulting in bone discomfort, stunted growth, and fragile bones that may result in bone abnormalities. However, adults can also suffer from a similar condition called osteomalacia, which results in fragile bones.

Usually, the main reason for rickets is a deficiency in vitamin D or calcium. While sunlight is the main source of Vitamin D, it can also be found in certain foods like oily fish and eggs. Children require Vitamin D to assist in the strengthening and proper formation of their bones. Children can sometimes be born with a genetic type of rickets. It may also occur when another illness hinders the body's absorption of nutrients.⁶

Other skeletal issues

• Curved spine in the opposite direction (lordosis)
• Curvature of the spine in a backwards and sideways direction (kyphoscoliosis)
• An extremely curved foot (pes cavus) or clubfoot.

ABL can result in the development of these skeletal deformities. As time passes, individuals may no longer have the capacity to stand or walk independently due to deteriorating neurological and skeletal conditions.⁷

Growth retardation

Growth failure in children

• Mechanisms that lead to growth failure are
  • Malabsorption of essential nutrients
  • Energy deficits and poor weight gain
• Clinical manifestations include
  • Stunted growth
  • Delayed development milestones

Interventions and management

• Nutritional support
  • Supplementation with fat-soluble vitamins (A, D, E, K)
  • Use of special formulas and diets
• Monitoring and follow-up
  • Regular bone density assessments
  • Growth tracking and developmental evaluations⁸

Diagnostic and therapeutic considerations

Blood tests to measure metabolic function 

Testing is conducted to diagnose metabolic alterations and assess the levels of vitamins A, D, E, and K. At times, apolipoprotein B levels may be assessed as well. Complete blood count and lipid levels are also analysed for a more thorough assessment.

Blood tests that analyse genetic information

An MTP gene test is required if there is a history of ABL. This can help to reach a diagnosis.

Additional examinations

Additional tests include stool samples, EMG, and eye examination. Also, a liver test is performed to identify abnormalities, whereas upper gastrointestinal endoscopy with intestinal biopsy is utilised to identify increased fat in epithelial cells. A liver biopsy is conducted to evaluate the fat buildup in the liver.⁹

Summary

Skeletal abnormalities seen in abetalipoproteinemia include osteopenia and osteoporosis, which signal a decrease in bone mineral density below normal levels, but not to a severe extent to be classified as osteoporosis.

Fluctuations in bone density are the primary way disease-causing factors influence the risk of future osteoporosis-related fractures.