NIH Rare Diseases
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54
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 71Disease definitionChylomicron retention disease (CRD) is a type of familial hypocholesterolemia characterized by malnutrition, failure to thrive, growth failure, vitamin E deficiency and hepatic, neurologic and ophthalmologic complications.EpidemiologyAbout 55 cases have been described to date.Clinical descriptionChylomicron retention disease manifests in infancy or early childhood. Features include an abnormal lipid profile, failure to thrive, chronic malabsorptive diarrhea, vomiting and abdominal distension in early infancy (1-6 months), and vitamin E deficiency. Cardiomyopathy and muscular manifestations have also been described. Essential fatty acid (EFA) deficiency is especially severe early in life. Poor mineralization and delayed bone maturation can occur. Hepatic steatosis is common and hepatomegaly is reported to occur in about 20% of CRD patients. Neurologic complications (areflexia, ataxia, myopathy, sensory neuropathy) and ophthalmologic complications (minor visual abnormalities) are less severe in CRD than in other types of familial hypocholesterolemia.EtiologyThe SAR1B gene has been identified as the cause of CRD. More than 14 different mutations in about 30 patients have been described. This gene encodes the Sar1b protein, which is involved in the transport of chylomicrons (carriers of dietary lipids) from the endoplasmic reticulum to the Golgi apparatus. This mutation results in accumulation of pre-chylomicron transport vesicles in the cytoplasm of enterocytes. Genotyping has revealed that Anderson's disease and CRD are in fact the same condition.Diagnostic methodsDiagnosis is often delayed because symptoms are nonspecific and hypocholesterolemia may be attributed to malnutrition secondary to chronic diarrhea. Diagnosis is based on a history of chronic diarrhea with fat malabsorption and a characteristic abnormal lipid profile: generally a 50% decrease in total cholesterol, LDL-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) in the presence of normal triglycerides. Upper endoscopy and histology reveal fat-laden enterocytes. Elevated creatine kinase (CK) in patients with hypocholesterolemia may be suggestive of CRD. Genotyping makes it possible to identify the SAR1B gene mutations. Parental lipid screening may clarify the diagnosis. An absence of hypocholesterolemia in both parents favors CRD. Consanguinity is frequent in patients with the disorder.Differential diagnosisDifferential diagnosis includes abetalipoproteinemia and other genetic hypocholesterolemias characterized by decreased LDL-C, such as homozygous hypobetalipoproteinemia (HBL; see these terms), and acquired disorders associated with low HDL-C.Genetic counselingThe disease follows an autosomal recessive pattern of inheritance.Management and treatmentFollow-up should be directed toward monitoring nutrition and growth, and treatment compliance. Management should focus on prevention and early detection of complications (hepatic, neuromuscular, retinal and bone). Control of vitamin E deficiency plays a key role in preventing neurological complications. Treatment includes fat-soluble vitamin supplements and large amounts of vitamin E. Vitamin A, in combination with vitamin E, may help to prevent ophthalmologic complications. Early vitamin D treatment makes it possible to prevent osteopenia. Vomiting, diarrhea and abdominal distension improve on a low-long chain fat diet. Dietary counseling is needed not only to monitor fat intake and improve symptoms, but also to maintain sufficient caloric and EFA intake.PrognosisVery long-term follow-up into adulthood is poorly documented.Visit the Orphanet disease page for more resources.
MalaCards based summary
:
Chylomicron Retention Disease, also known as
cmrd, is related to
hypobetalipoproteinemia, familial, 2 and
hypolipoproteinemia, and has symptoms including
nausea and vomiting,
constipation and
vomiting. An important gene associated with Chylomicron Retention Disease is
SAR1B (Secretion Associated Ras Related GTPase 1B), and among its related pathways/superpathways are
Protein processing in endoplasmic reticulum and
Metabolism. Affiliated tissues include
bone,
eye and
lung, and related phenotypes are
diarrhea and
hypocholesterolemia
Disease Ontology
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12
A lipid metabolism disorder characterized by malnutrition, failure to thrive, growth failure, vitamin E deficiency and the absence of chylomicrons and apolipoprotein B48 post-prandially. It has an autosomal recessive inheritance pattern and has material basis in mutations in the SAR1B gene on chromosome 5q31.1.
Genetics Home Reference
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26
Chylomicron retention disease is an inherited disorder that impairs the normal absorption of fats, cholesterol, and certain vitamins from food. The features of chylomicron retention disease primarily affect the gastrointestinal system and nervous system.
OMIM
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58
Chylomicron retention disease is an autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy (Dannoura et al., 1999).
(246700)
UniProtKB/Swiss-Prot
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76
Chylomicron retention disease: An autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy. The condition is characterized by deficiency of fat-soluble vitamins, low blood cholesterol levels, and a selective absence of chylomicrons from blood. Affected individuals accumulate chylomicron-like particles in membrane-bound compartments of enterocytes, which contain large cytosolic lipid droplets.
Wikipedia
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77
Chylomicron retention disease is a disorder of fat absorption. It is associated with SAR1B. Mutations in...
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