Chylomicron Retention Disease
Disease Details
Family Health Simplified
- Description
- Chylomicron retention disease is a rare inherited disorder characterized by the body's inability to properly absorb and transport dietary fats.
- Type
- Chylomicron retention disease is transmitted in an autosomal recessive manner.
- Signs And Symptoms
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Physical symptoms of CMRD involving the development and function of the gastrointestinal tract and nervous system typically manifest between infancy and adolescence. The symptoms of CmRD are similar to the physical symptoms of malnutrition, as the disease arises due to the poor absorption of lipids and fat-soluble nutrients such as vitamin E. For this reason, the disease is likely to be underdiagnosed by physicians. Fat-soluble nutrients are essential for growth, development, and normal bodily function. Vitamin E deficiency is especially serious, as the vitamin is necessary for proper neurological function and development. Without Vitamin E, neurons cannot operate correctly and signals from the brain are weakened. This leads to reduced muscle development and reduced muscle contraction.
Symptoms that manifest in the GI tract are likely to be a consequence of both reduced absorption of fats and physiological stress imposed on enterocytes that can not shuttle fats into circulation. Additional symptoms that occur throughout the body can be attributed to the lack of sufficient lipid sources.
Chronic Malabsorptive Diarrhea- Diarrhea that results from the poor absorption of fats
Steatorrhea- Abnormal stools, often foul smelling, due to the increased presence of undigested fats
Vomiting
Vitamin E deficiency- Low levels of Vitamin E due to the malabsorption of fats in the diet, causes poor brain, muscle, and eye development.
Cardiomyopathy- A class of diseases that affects heart muscle, causing shortness of breath, tiredness, and swelling of the legs
Slowed Growth
Failure to thrive- Insufficient weight gain, or drastic levels of weight loss in children
Hypocholesterolemia- Low blood cholesterol levels
Hepatic Steatosis (Fatty Liver)- Excessive fat buildup in the liver, a result of the abnormal lipid panels of CMRD patients
Hyporeflexia- Absent or low levels of muscle reflexes
Amyotrophy- Muscle tissue "wasting," the loss of muscle tissue - Prognosis
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As of March 2020, only 50 cases of CMRD have been documented in the medical literature. This small number speaks to the rarity of the disease as well as the lack of thorough research and documentation. As a result, the full course of the disease, life expectancy, and mortality are also poorly documented.
Clinical manifestation of CMRD symptoms begin during infancy and early childhood but may go undetected due to the non-specific symptoms associated with the disease. Many of these symptoms can be attributed to malnutrition and nonspecific postnatal diarrhea, confounding early diagnosis. Careful regulation of diet and nutrition are required for management of CMRD since the disease results from the poor absorption of nutrients from food. - Onset
- For chylomicron retention disease (CMRD), the onset typically occurs in infancy or early childhood. Symptoms may include chronic diarrhea, failure to thrive, fat malabsorption, and deficiencies in fat-soluble vitamins.
- Prevalence
- Chylomicron retention disease, also known as Anderson's disease, is an extremely rare genetic disorder. The exact prevalence is not well-established due to its rarity, but it is considered to affect fewer than 1 in 1,000,000 individuals globally.
- Epidemiology
- Chylomicron retention disease (CRD), also known as Anderson's disease, is an extremely rare genetic disorder. The precise prevalence is not well-established due to its rarity. It typically presents in infancy or early childhood, often diagnosed through symptoms such as chronic diarrhea, failure to thrive, and fat malabsorption.
- Intractability
- Chylomicron retention disease (CMRD) is relatively intractable due to its genetic basis. Management primarily focuses on dietary modifications, such as a low-fat diet and fat-soluble vitamin supplementation, but there is no cure currently available. Lifelong adherence to these interventions is typically necessary to manage symptoms and complications.
- Disease Severity
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Chylomicron retention disease, also known as Anderson's disease, is a rare genetic disorder characterized by the body's inability to effectively absorb fats, cholesterol, and fat-soluble vitamins from the diet. Disease severity can vary:
1. **Mild**: Patients might experience subtle symptoms such as mild gastrointestinal discomfort and slight growth delays.
2. **Moderate**: More noticeable symptoms arise, including chronic diarrhea, steatorrhea (fatty stools), poor weight gain, and vitamin deficiencies that can affect growth and development.
3. **Severe**: Significant malnutrition, severe growth retardation, failure to thrive, and serious complications due to vitamin deficiencies, such as neuropathy (nerve damage), anemia, and bone abnormalities.
Early diagnosis and appropriate dietary management, including supplementation of fat-soluble vitamins and medium-chain triglycerides, are crucial for reducing disease severity and improving quality of life. - Healthcare Professionals
- Disease Ontology ID - DOID:0060357
- Pathophysiology
- Chylomicron retention disease, also known as Anderson's disease, is a rare genetic disorder characterized by an inability to properly form and secrete chylomicrons, which are lipoproteins responsible for the transportation of dietary fats and fat-soluble vitamins from the intestines to other parts of the body. The pathophysiology involves mutations in the SAR1B gene, which encodes a protein essential for the transport of chylomicrons out of the enterocytes (intestinal cells). As a result, lipids accumulate within enterocytes, leading to fat malabsorption, steatorrhea (fatty stools), and deficiencies in fat-soluble vitamins (A, D, E, and K). This can cause various clinical manifestations, including growth retardation, diarrhea, and neurological symptoms due to vitamin deficiencies.
- Carrier Status
- Chylomicron retention disease is an autosomal recessive disorder. Carrier status for autosomal recessive diseases means that an individual carries one copy of the mutated gene but does not typically show symptoms of the disease. Carriers can pass the mutated gene to their offspring, who might develop the disease if they inherit two copies of the mutated gene (one from each parent).
- Mechanism
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Chylomicron retention disease (CMRD), also known as Anderson's disease, is a rare genetic disorder that affects the body's ability to absorb dietary fats, cholesterol, and certain vitamins.
**Mechanism:**
In CMRD, the primary defect occurs in the enterocytes, the absorptive cells in the lining of the small intestine. Normally, after dietary fats are digested, they are packaged into lipoprotein particles called chylomicrons in the enterocytes and then secreted into the lymphatic system for transport to the bloodstream. In individuals with CMRD, this process is disrupted, leading to the retention of chylomicrons within the enterocytes. This results in malabsorption of dietary fats and fat-soluble vitamins, which can lead to various clinical symptoms such as failure to thrive, chronic diarrhea, steatorrhea (fatty stools), and deficiencies in vitamins A, D, E, and K.
**Molecular Mechanisms:**
CMRD is primarily caused by mutations in the SAR1B gene, which encodes the SAR1B protein, a small GTPase that is critical for transport vesicle formation from the endoplasmic reticulum (ER). The SAR1B protein plays a crucial role in the COPII complex, which is involved in the transport of proteins and lipids from the ER to the Golgi apparatus. Mutations in SAR1B disrupt this process, preventing the proper packaging and secretion of chylomicrons. As a result, chylomicrons accumulate within the enterocytes, interfering with the normal absorption and transport of dietary fats. This molecular defect underscores the vital role of SAR1B in lipid metabolism and gut physiology. - Treatment
- It is recommended that patients with CMRD follow a strict low-fat diet in addition to fat-soluble vitamin supplementation. The fat soluble vitamins are A,D,E, and K. A combination of vitamin A and vitamin E are effective for combating ophthalmologic complications. When vitamin D is administered early, it aids in preventing osteopenia. People with CMRD are at an increased risk for essential fatty acid deficiency, so dietary counseling is required to maintain the low-fat diet, while attaining sufficient caloric intake and essential fatty acid intake.
- Compassionate Use Treatment
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Chylomicron retention disease (CMRD) is a rare inherited disorder characterized by the improper absorption and transport of dietary fats. For compassionate use or off-label treatments, some approaches may include:
1. **Vitamin Supplementation**: High doses of fat-soluble vitamins (A, D, E, and K) are often recommended to address deficiencies caused by impaired absorption.
2. **Medium-Chain Triglycerides (MCTs)**: MCTs can be added to the diet because they are absorbed directly into the portal circulation and do not require chylomicron formation for transport.
3. **Fat-Restricted Diet**: A diet low in long-chain fatty acids can help manage symptoms by reducing the burden on the defective chylomicron retention mechanisms.
4. **Antioxidant Therapy**: There is some experimental interest in using antioxidants to mitigate oxidative stress caused by fat malabsorption.
5. **Clinical Trials**: Participation in clinical trials that explore new treatments for CMRD may provide access to experimental therapies not otherwise available.
Consultation with a specialist in metabolic disorders or a clinical geneticist is essential for managing CMRD and exploring these treatment options. - Lifestyle Recommendations
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For Chylomicron Retention Disease (Anderson's disease), lifestyle recommendations include:
1. **Dietary Modifications**:
- A low-fat diet rich in medium-chain triglycerides (MCTs) is often recommended. MCTs are absorbed directly into the bloodstream without the need for chylomicron formation.
- Avoid long-chain triglycerides, as the body cannot process them effectively.
- Small, frequent meals can help manage symptoms and ensure adequate nutrient absorption.
- Supplement fat-soluble vitamins (A, D, E, and K) as these are often deficient due to malabsorption issues.
2. **Regular Monitoring**:
- Regular follow-ups with healthcare providers to monitor nutritional status and overall health.
3. **Physical Activity**:
- Engage in regular physical activity as tolerated. This can help maintain overall health, though it's important to ensure nutritional needs are met to support physical activity.
4. **Support Systems**:
- Consider joining support groups for individuals with rare diseases, which can provide emotional support and practical advice.
It is crucial to work with a healthcare team, including a dietitian, to tailor these recommendations to individual needs. - Medication
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Chylomicron retention disease (CMRD), also known as Anderson's disease, is a rare genetic disorder affecting the body's ability to properly absorb dietary fats, cholesterol, and fat-soluble vitamins. The management of CMRD primarily involves dietary modifications rather than specific medications. Key elements include:
1. **Low-Fat Diet**: Reducing dietary fat intake to minimize symptoms.
2. **Supplementation**: Ensuring adequate intake of fat-soluble vitamins (A, D, E, K) in water-soluble forms.
3. **Medium-Chain Triglycerides (MCTs)**: These can be better absorbed and used as an alternative energy source.
Medications are generally not the primary treatment but may be used to manage specific symptoms as needed. - Repurposable Drugs
- Chylomicron retention disease (CMRD), also known as Anderson’s disease, is a rare genetic disorder affecting the absorption and transport of dietary fats. Due to its rarity and specificity, there are no well-established repurposable drugs currently identified for this condition. Treatments are generally focused on dietary modifications, including a low-fat diet supplemented with fat-soluble vitamins (A, D, E, K) and medium-chain triglycerides, which are more easily absorbed. Further research is necessary to explore potential therapeutic options, including repurposing existing medications from other indications.
- Metabolites
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Chylomicron retention disease (CRD) is a rare genetic disorder that affects the metabolism of lipids. Individuals with CRD typically exhibit abnormalities in their blood lipid profiles, including:
- Elevated levels of certain fatty acids and triglycerides in intestinal mucosal cells.
- Reduced levels of chylomicrons, which are lipoproteins responsible for transporting dietary lipids from the intestines to other tissues.
- Low levels of plasma lipid metabolites such as triglycerides and cholesterol due to impaired chylomicron formation and release.
Nutritional absorption notably involves deficiencies in fat-soluble vitamins (A, D, E, and K) due to impaired lipid absorption. Additionally, CRD patients typically exhibit normal plasma levels of other metabolites, related to proteins and carbohydrates, highlighting the specificity of the lipid metabolism defect. - Nutraceuticals
- Chylomicron retention disease (CRD), also known as Anderson's disease, is a rare genetic disorder affecting lipid metabolism. Currently, there are limited specific nutraceuticals proven to treat CRD directly. However, management of the condition often includes dietary adjustments and vitamin supplementation. This primarily involves a low-fat diet and supplementation with fat-soluble vitamins (A, D, E, and K), as individuals with CRD have difficulty absorbing these nutrients. Always consult with a healthcare professional for tailored advice.
- Peptides
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For chylomicron retention disease (CRD), also known as Anderson's disease, specific peptides are not typically associated with its diagnosis or treatment. The disease is primarily caused by mutations in the SAR1B gene, which affects the secretion of chylomicrons from enterocytes.
The term "nan" isn't commonly associated with this condition. If referring to "nan" as not a number or not applicable, it may indicate there's no relevant information related to peptides in the context of CRD. The primary focus for managing CRD lies in dietary modifications, such as a low-fat diet supplemented with fat-soluble vitamins, rather than peptide-based treatments.