Homozygous familial sitosterolaemia Treatment in UAE

Overview Of Homozygous familial sitosterolaemia

Homozygous familial sitosterolaemia, also known as phytosterolaemia or sitosterolaemia, is a rare autosomal recessive metabolic disorder characterized by the abnormal accumulation of plant sterols (phytosterols) in the blood and tissues. This condition results from mutations in the ABCG5 or ABCG8 genes, which encode proteins responsible for limiting the absorption of dietary sterols and promoting their excretion from the body. In affected individuals, these mutations lead to increased absorption of plant sterols (such as sitosterol) and reduced excretion, causing elevated levels of these sterols in the plasma. This accumulation can lead to the development of xanthomas (cholesterol deposits in the skin and tendons), premature atherosclerosis, and cardiovascular complications. The condition is typically diagnosed in childhood or early adulthood and requires lifelong management to prevent complications.

Symptoms of Homozygous familial sitosterolaemia

The symptoms of homozygous familial sitosterolaemia can vary in severity and may include:
Xanthomas: Cholesterol-rich deposits in the skin, tendons, and other tissues, often appearing as yellowish nodules or plaques.
Premature Atherosclerosis: Accelerated buildup of plaque in the arteries, leading to an increased risk of cardiovascular events such as heart attacks or strokes.
Hematologic Abnormalities: Hemolytic anemia or macrothrombocytopenia (enlarged platelets) due to the effects of sterol accumulation on red blood cells and platelets.
Arthralgia and Arthritis: Joint pain and inflammation caused by sterol deposition in joint tissues.
Hepatic Dysfunction: Liver involvement, including hepatomegaly (enlarged liver) or elevated liver enzymes.
Ophthalmic Manifestations: Rarely, corneal arcus (a white or gray ring around the cornea) may be observed. Symptoms often appear in childhood or adolescence, but milder cases may not be diagnosed until adulthood.

Causes of Homozygous familial sitosterolaemia

Homozygous familial sitosterolaemia is caused by mutations in the ABCG5 or ABCG8 genes, which are located on chromosome
These genes encode for sterolin-1 and sterolin-2, respectively, which form a heterodimeric transporter complex in the liver and intestines. This complex plays a critical role in limiting the absorption of dietary sterols and promoting their excretion into the bile. Mutations in either gene disrupt the function of this transporter, leading to excessive absorption of plant sterols (e.g., sitosterol, campesterol) and reduced excretion. As a result, phytosterols accumulate in the blood and tissues, contributing to the clinical manifestations of the disease. The condition is inherited in an autosomal recessive pattern, meaning that an individual must inherit two defective copies of the gene (one from each parent) to develop the disorder.

Risk Factors of Homozygous familial sitosterolaemia

The primary risk factor for homozygous familial sitosterolaemia is having two parents who are carriers of mutations in the ABCG5 or ABCG8 genes. Other risk factors include:
Family History: A family history of the condition or consanguineous marriages increases the likelihood of inheriting two defective copies of the gene.
Dietary Intake: High consumption of plant-based foods rich in phytosterols (e.g., vegetable oils, nuts, seeds) can exacerbate the condition.
Ethnicity: Certain populations, such as those of Japanese or Amish descent, have a higher prevalence of the disorder due to founder mutations.
Age: Symptoms often manifest in childhood or early adulthood, making early screening important in at-risk individuals.

Prevention of Homozygous familial sitosterolaemia

Preventing complications in homozygous familial sitosterolaemia involves early diagnosis and strict adherence to treatment. Key preventive measures include:
Newborn Screening: Early identification through genetic testing or plasma sterol analysis in at-risk families.
Dietary Management: Avoiding foods high in plant sterols to minimize absorption.
Regular Monitoring: Frequent assessment of plasma sterol levels and cardiovascular health to guide treatment adjustments.
Genetic Counseling: Providing information and support to families to understand the inheritance pattern and risks for future pregnancies.

Prognosis of Homozygous familial sitosterolaemia

The prognosis for individuals with homozygous familial sitosterolaemia depends on the severity of the condition and the timeliness of diagnosis and treatment. With early intervention and strict adherence to dietary and medical therapies, many patients can achieve significant reductions in plasma sterol levels and prevent the progression of complications such as atherosclerosis and xanthomas. However, untreated or poorly managed cases can lead to severe cardiovascular disease, disability, or premature death. Regular monitoring of sterol levels and cardiovascular health is critical for optimizing outcomes.

Complications of Homozygous familial sitosterolaemia

Complications of homozygous familial sitosterolaemia include:
Cardiovascular Disease: Accelerated atherosclerosis increases the risk of heart attacks, strokes, and peripheral artery disease.
Xanthomas: These deposits can cause cosmetic concerns, pain, or functional impairment if they occur in critical areas like tendons or joints.
Hematologic Issues: Hemolytic anemia or macrothrombocytopenia can lead to fatigue, bleeding, or other complications.
Liver Dysfunction: Chronic liver involvement may progress to fibrosis or cirrhosis in severe cases.
Psychosocial Impact: The physical manifestations and dietary restrictions associated with the condition can affect quality of life and mental health.

Related Diseases of Homozygous familial sitosterolaemia

Homozygous familial sitosterolaemia is related to several other lipid metabolism disorders and genetic conditions, including:
Familial Hypercholesterolemia: A condition characterized by high levels of LDL cholesterol due to mutations in the LDL receptor gene.
Cerebrotendinous Xanthomatosis: A rare disorder involving the accumulation of cholestanol and cholesterol in tissues, caused by mutations in the CYP27A1 gene.
Smith-Lemli-Opitz Syndrome: A genetic disorder affecting cholesterol synthesis due to mutations in the DHCR7 gene.
Abetalipoproteinemia: A condition characterized by the inability to absorb dietary fats and fat-soluble vitamins, leading to low cholesterol levels.
Tangier Disease: A disorder caused by mutations in the ABCA1 gene, leading to low HDL cholesterol and cholesterol accumulation in tissues. Understanding these related conditions can aid in differential diagnosis and management.

Treatment of Homozygous familial sitosterolaemia

The treatment of homozygous familial sitosterolaemia focuses on reducing the absorption of dietary sterols and promoting their excretion. Key treatment strategies include: 1. **Dietary Modifications**: Restricting intake of foods high in plant sterols, such as vegetable oils, nuts, seeds, and certain fortified products. 2. **Bile Acid Sequestrants**: Medications like cholestyramine or colestipol bind to bile acids in the intestines, reducing sterol absorption. 3. **Ezetimibe**: This cholesterol absorption inhibitor blocks the NPC1L1 transporter in the intestines, further reducing sterol uptake. 4. **Statins**: While not directly targeting phytosterols, statins may be used to manage associated hypercholesterolemia. 5. **Liver Transplantation**: In severe cases, liver transplantation may be considered to restore normal sterol metabolism. Lifelong adherence to treatment is essential to prevent complications.