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Hyperlipoproteinemia, type 1D

MedGen UID:
863204
Concept ID:
C4014767
Disease or Syndrome
Synonym: Hyperlipoproteinemia, type ID
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): GPIHBP1 (8q24.3)
 
Monarch Initiative: MONDO:0014412
OMIM®: 615947
Orphanet: ORPHA535458

Definition

Hyperlipoproteinemia type ID is a rare autosomal recessive disorder characterized by impaired clearance of triglyceride (TG)-rich lipoproteins in plasma, leading to severe hypertriglyceridemia (chylomicronemia). Clinical features include eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, episodes of abdominal pain, and pancreatitis. Onset usually occurs in adulthood (summary by Brahm and Hegele, 2013). For a discussion of genetic heterogeneity of familial chylomicronemia, see 238600. [from OMIM]

Clinical features

From HPO
Premature coronary artery atherosclerosis
MedGen UID:
356830
Concept ID:
C1867743
Disease or Syndrome
Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries before age of 45.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Colitis
MedGen UID:
40385
Concept ID:
C0009319
Disease or Syndrome
Ulcerative colitis is a chronic disorder that affects the digestive system. This condition is characterized by abnormal inflammation of the inner surface (epithelium) of the rectum and colon. The rectum and colon make up most of the length of the large intestine. The inflammation usually causes open sores (ulcers) to develop in the large intestine. Ulcerative colitis usually appears between the age of 15 and 30, although it can develop at any age. The inflammation tends to flare up multiple times throughout a person's life, which causes recurring signs and symptoms.\n\nThe most common symptoms of ulcerative colitis are cramping abdominal pain and frequent diarrhea, often with blood, pus, or mucus in the stool. Other signs and symptoms include nausea, loss of appetite, bowel urgency, fatigue, and fevers. Chronic bleeding from the inflamed and ulcerated intestinal tissue can cause a shortage of red blood cells (anemia) in some affected individuals. People with this disorder have difficulty absorbing enough fluids and nutrients from their diet and often experience weight loss. Affected children usually grow more slowly than normal. Less commonly, ulcerative colitis causes problems with the skin, joints, eyes, kidneys, or liver, which are most likely due to abnormal inflammation.\n\nToxic megacolon is a rare complication of ulcerative colitis that can be life-threatening. Toxic megacolon involves a widening (dilation) of the colon and an overwhelming inflammatory response. Ulcerative colitis also increases the risk of developing colon cancer, especially in people whose entire colon is inflamed and in those who have had ulcerative colitis for 8 years or more.\n\nUlcerative colitis is one common form of inflammatory bowel disease (IBD). Another type of IBD, Crohn's disease, also causes chronic inflammation of the intestines. Unlike ulcerative colitis, which affects only the inner surface of the large intestine, Crohn's disease can cause inflammation in any part of the digestive system, and the inflammation extends deeper into the intestinal tissue.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Pancreatitis
MedGen UID:
14586
Concept ID:
C0030305
Disease or Syndrome
The presence of inflammation in the pancreas.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Recurrent pancreatitis
MedGen UID:
1639431
Concept ID:
C4551632
Disease or Syndrome
A recurrent form of pancreatitis.
Hyperlipoproteinemia
MedGen UID:
9363
Concept ID:
C0020476
Disease or Syndrome
An abnormal increase in the level of lipoprotein cholesterol in the blood.
Decreased HDL cholesterol concentration
MedGen UID:
57731
Concept ID:
C0151691
Finding
An decreased concentration of high-density lipoprotein cholesterol in the blood.
Hypertriglyceridemia
MedGen UID:
167238
Concept ID:
C0813230
Finding
An abnormal increase in the level of triglycerides in the blood.
Decreased LDL cholesterol concentration
MedGen UID:
776554
Concept ID:
C0853085
Finding
An decreased concentration of low-density lipoprotein cholesterol in the blood.
Increased circulating chylomicron concentration
MedGen UID:
853340
Concept ID:
C1535978
Finding
Increased plasma concentrations of chylomicrons, the large lipid droplet (up to 100 mm in diameter) of reprocessed lipid synthesized in epithelial cells of the small intestine and containing triacylglycerols, cholesterol esters, and several apolipoproteins.
Eruptive xanthomas
MedGen UID:
66366
Concept ID:
C0221252
Disease or Syndrome
Eruptive xanthomas are yellow-orange-to-red-brown papules that are often surrounded by an erythematous halo. They appear in crops on the buttocks, extensor surfaces of the extremities, and flexural creases. Acutely, variable amounts of pruritus and pain occur.
Lipemia retinalis
MedGen UID:
137918
Concept ID:
C0339477
Disease or Syndrome
A creamy appearance of the retinal blood vessels that occurs when the concentration of lipids in the blood are extremely increased, with pale pink to milky white retinal vessels and altered pale reflexes from choroidal vasculature.

Professional guidelines

PubMed

Am J Cardiol 1993 Sep 30;72(10):1D-84D. PMID: 8105672
Bild DE, Williams RR, Brewer HB, Herd JA, Pearson TA, Stein E
Am J Cardiol 1993 Sep 30;72(10):1D-5D. doi: 10.1016/0002-9149(93)90002-t. PMID: 8105671

Recent clinical studies

Etiology

Romanelli F, Corbo A, Salehi M, Yadav MC, Salman S, Petrosian D, Rashidbaigi OJ, Chait J, Kuruvilla J, Plummer M, Radichev I, Margulies KB, Gerdes AM, Pinkerton AB, Millán JL, Savinov AY, Savinova OV
PLoS One 2017;12(10):e0186426. Epub 2017 Oct 12 doi: 10.1371/journal.pone.0186426. PMID: 29023576Free PMC Article
Bild DE, Williams RR, Brewer HB, Herd JA, Pearson TA, Stein E
Am J Cardiol 1993 Sep 30;72(10):1D-5D. doi: 10.1016/0002-9149(93)90002-t. PMID: 8105671
Lee DM, Downs D
J Lipid Res 1982 Jan;23(1):14-27. PMID: 6799599
Angelin B, Einarsson K, Hellström K, Leijd B
J Lipid Res 1978 Nov;19(8):1004-16. PMID: 731122

Diagnosis

Am J Cardiol 1993 Sep 30;72(10):1D-84D. PMID: 8105672
Bild DE, Williams RR, Brewer HB, Herd JA, Pearson TA, Stein E
Am J Cardiol 1993 Sep 30;72(10):1D-5D. doi: 10.1016/0002-9149(93)90002-t. PMID: 8105671

Therapy

Trifiletti A, Lasco A, Scamardi R, Pizzoleo MA, Gaudio A, La Rocca R, Morini E, Frisina N
Pathophysiol Haemost Thromb 2003 Mar-Apr;33(2):84-7. doi: 10.1159/000073851. PMID: 14624049

Prognosis

Romanelli F, Corbo A, Salehi M, Yadav MC, Salman S, Petrosian D, Rashidbaigi OJ, Chait J, Kuruvilla J, Plummer M, Radichev I, Margulies KB, Gerdes AM, Pinkerton AB, Millán JL, Savinov AY, Savinova OV
PLoS One 2017;12(10):e0186426. Epub 2017 Oct 12 doi: 10.1371/journal.pone.0186426. PMID: 29023576Free PMC Article
Schaefer JR, Winkler K, Schweer H, Hoffmann MM, Soufi M, Scharnagl H, Maisch B, Wieland H, Steinmetz A, März W
Arterioscler Thromb Vasc Biol 2000 Jul;20(7):1796-9. doi: 10.1161/01.atv.20.7.1796. PMID: 10894819

Clinical prediction guides

Romanelli F, Corbo A, Salehi M, Yadav MC, Salman S, Petrosian D, Rashidbaigi OJ, Chait J, Kuruvilla J, Plummer M, Radichev I, Margulies KB, Gerdes AM, Pinkerton AB, Millán JL, Savinov AY, Savinova OV
PLoS One 2017;12(10):e0186426. Epub 2017 Oct 12 doi: 10.1371/journal.pone.0186426. PMID: 29023576Free PMC Article

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