U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Sea-blue histiocyte syndrome

MedGen UID:
19908
Concept ID:
C0036489
Disease or Syndrome
Synonyms: Inherited Lipemic Splenomegaly; Sea-Blue histiocyte disease; Sea-blue histiocytosis
SNOMED CT: Sea-blue histiocyte syndrome (37821003); Sea-blue histiocytosis (37821003)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): APOE (19q13.32)
 
HPO: HP:0001982
Monarch Initiative: MONDO:0010017
OMIM®: 269600
Orphanet: ORPHA158029

Definition

An abnormality of histiocytes, in which the cells take on a sea blue appearance due to abnormally increased lipid content. Histiocytes are a type of macrophage. Sea-blue histiocytes are typically large macrophages from 20 to 60 micrometers in diameter with a single eccentric nucleus whose cytoplasm if packed with sea-blue or blue-green granules when stained with Wright-Giemsa. [from HPO]

Clinical features

From HPO
Foam cells
MedGen UID:
924121
Concept ID:
C4281786
Finding
The presence of foam cells, a type of macrophage that localizes to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Sea-blue histiocyte syndrome
MedGen UID:
19908
Concept ID:
C0036489
Disease or Syndrome
An abnormality of histiocytes, in which the cells take on a sea blue appearance due to abnormally increased lipid content. Histiocytes are a type of macrophage. Sea-blue histiocytes are typically large macrophages from 20 to 60 micrometers in diameter with a single eccentric nucleus whose cytoplasm if packed with sea-blue or blue-green granules when stained with Wright-Giemsa.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Absent axillary hair
MedGen UID:
347869
Concept ID:
C1859392
Finding
Absence of axillary hair.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSea-blue histiocyte syndrome
Follow this link to review classifications for Sea-blue histiocyte syndrome in Orphanet.

Conditions with this feature

Sea-blue histiocyte syndrome
MedGen UID:
19908
Concept ID:
C0036489
Disease or Syndrome
An abnormality of histiocytes, in which the cells take on a sea blue appearance due to abnormally increased lipid content. Histiocytes are a type of macrophage. Sea-blue histiocytes are typically large macrophages from 20 to 60 micrometers in diameter with a single eccentric nucleus whose cytoplasm if packed with sea-blue or blue-green granules when stained with Wright-Giemsa.
Niemann-Pick disease, type A
MedGen UID:
78650
Concept ID:
C0268242
Disease or Syndrome
The phenotype of acid sphingomyelinase deficiency (ASMD) occurs along a continuum. Individuals with the severe early-onset form, infantile neurovisceral ASMD, were historically diagnosed with Niemann-Pick disease type A (NPD-A). The later-onset, chronic visceral form of ASMD is also referred to as Niemann-Pick disease type B (NPD-B). A phenotype with intermediate severity is also known as chronic neurovisceral ASMD (NPD-A/B). The most common presenting symptom in NPD-A is hepatosplenomegaly, usually detectable by age three months; over time the liver and spleen become massive in size. Psychomotor development progresses no further than the 12-month level, after which neurologic deterioration is relentless. Failure to thrive typically becomes evident by the second year of life. A classic cherry-red spot of the macula of the retina, which may not be present in the first few months, is eventually present in all affected children. Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. Most children succumb before the third year of life. NPD-B generally presents later than NPD-A, and the manifestations are less severe. NPD-B is characterized by progressive hepatosplenomegaly, gradual deterioration in liver and pulmonary function, osteopenia, and atherogenic lipid profile. No central nervous system (CNS) manifestations occur. Individuals with NPD-A/B have symptoms that are intermediate between NPD-A and NPD-B. The presentation in individuals with NPD-A/B varies greatly, although all are characterized by the presence of some CNS manifestations. Survival to adulthood can occur in individuals with NPD-B and NPD-A/B.
Niemann-Pick disease, type B
MedGen UID:
78651
Concept ID:
C0268243
Disease or Syndrome
The phenotype of acid sphingomyelinase deficiency (ASMD) occurs along a continuum. Individuals with the severe early-onset form, infantile neurovisceral ASMD, were historically diagnosed with Niemann-Pick disease type A (NPD-A). The later-onset, chronic visceral form of ASMD is also referred to as Niemann-Pick disease type B (NPD-B). A phenotype with intermediate severity is also known as chronic neurovisceral ASMD (NPD-A/B). The most common presenting symptom in NPD-A is hepatosplenomegaly, usually detectable by age three months; over time the liver and spleen become massive in size. Psychomotor development progresses no further than the 12-month level, after which neurologic deterioration is relentless. Failure to thrive typically becomes evident by the second year of life. A classic cherry-red spot of the macula of the retina, which may not be present in the first few months, is eventually present in all affected children. Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. Most children succumb before the third year of life. NPD-B generally presents later than NPD-A, and the manifestations are less severe. NPD-B is characterized by progressive hepatosplenomegaly, gradual deterioration in liver and pulmonary function, osteopenia, and atherogenic lipid profile. No central nervous system (CNS) manifestations occur. Individuals with NPD-A/B have symptoms that are intermediate between NPD-A and NPD-B. The presentation in individuals with NPD-A/B varies greatly, although all are characterized by the presence of some CNS manifestations. Survival to adulthood can occur in individuals with NPD-B and NPD-A/B.
GM1 gangliosidosis type 2
MedGen UID:
120625
Concept ID:
C0268272
Disease or Syndrome
GLB1-related disorders comprise two phenotypically distinct lysosomal storage disorders: GM1 gangliosidosis and mucopolysaccharidosis type IVB (MPS IVB). The phenotype of GM1 gangliosidosis constitutes a spectrum ranging from severe (infantile) to intermediate (late-infantile and juvenile) to mild (chronic/adult). Type I (infantile) GM1 gangliosidosis begins before age 12 months. Prenatal manifestations may include nonimmune hydrops fetalis, intrauterine growth restriction, and placental vacuolization; congenital dermal melanocytosis (Mongolian spots) may be observed. Macular cherry-red spot is detected on eye exam. Progressive central nervous system dysfunction leads to spasticity and rapid regression; blindness, deafness, decerebrate rigidity, seizures, feeding difficulties, and oral secretions are observed. Life expectancy is two to three years. Type II can be subdivided into the late-infantile (onset age 1-3 years) and juvenile (onset age 3-10 years) phenotypes. Central nervous system dysfunction manifests as progressive cognitive, motor, and speech decline as measured by psychometric testing. There may be mild corneal clouding, hepatosplenomegaly, and/or cardiomyopathy; the typical course is characterized by progressive neurologic decline, progressive skeletal disease in some individuals (including kyphosis and avascular necrosis of the femoral heads), and progressive feeding difficulties leading to aspiration risk. Type III begins in late childhood to the third decade with generalized dystonia leading to unsteady gait and speech disturbance followed by extrapyramidal signs including akinetic-rigid parkinsonism. Cardiomyopathy develops in some and skeletal involvement occurs in most. Intellectual impairment is common late in the disease with prognosis directly related to the degree of neurologic impairment. MPS IVB is characterized by skeletal dysplasia with specific findings of axial and appendicular dysostosis multiplex, short stature (below 15th centile in adults), kyphoscoliosis, coxa/genu valga, joint laxity, platyspondyly, and odontoid hypoplasia. First signs and symptoms may be apparent at birth. Bony involvement is progressive, with more than 84% of adults requiring ambulation aids; life span does not appear to be limited. Corneal clouding is detected in some individuals and cardiac valvular disease may develop.
Niemann-Pick disease, type C2
MedGen UID:
335942
Concept ID:
C1843366
Disease or Syndrome
Niemann-Pick disease type C (NPC) is a slowly progressive lysosomal disorder whose principal manifestations are age dependent. The manifestations in the perinatal period and infancy are predominantly visceral, with hepatosplenomegaly, jaundice, and (in some instances) pulmonary infiltrates. From late infancy onward, the presentation is dominated by neurologic manifestations. The youngest children may present with hypotonia and developmental delay, with the subsequent emergence of ataxia, dysarthria, dysphagia, and, in some individuals, epileptic seizures, dystonia, and gelastic cataplexy. Although cognitive impairment may be subtle at first, it eventually becomes apparent that affected individuals have a progressive dementia. Older teenagers and young adults may present predominantly with apparent early-onset dementia or psychiatric manifestations; however, careful examination usually identifies typical neurologic signs.
Niemann-Pick disease, type C1
MedGen UID:
465922
Concept ID:
C3179455
Disease or Syndrome
Niemann-Pick disease type C (NPC) is a slowly progressive lysosomal disorder whose principal manifestations are age dependent. The manifestations in the perinatal period and infancy are predominantly visceral, with hepatosplenomegaly, jaundice, and (in some instances) pulmonary infiltrates. From late infancy onward, the presentation is dominated by neurologic manifestations. The youngest children may present with hypotonia and developmental delay, with the subsequent emergence of ataxia, dysarthria, dysphagia, and, in some individuals, epileptic seizures, dystonia, and gelastic cataplexy. Although cognitive impairment may be subtle at first, it eventually becomes apparent that affected individuals have a progressive dementia. Older teenagers and young adults may present predominantly with apparent early-onset dementia or psychiatric manifestations; however, careful examination usually identifies typical neurologic signs.

Recent clinical studies

Etiology

Newman B, Hu W, Nigro K, Gilliam AC
J Am Acad Dermatol 2007 Feb;56(2):302-16. Epub 2006 Oct 9 doi: 10.1016/j.jaad.2006.06.010. PMID: 17097374
Howard MR, Kesteven PJ
J Clin Pathol 1993 Nov;46(11):1030-2. doi: 10.1136/jcp.46.11.1030. PMID: 8254090Free PMC Article
Lee RE
Hematol Oncol Clin North Am 1988 Dec;2(4):657-67. PMID: 3220804
Yan-Go FL, Yanagihara T, Pierre RV, Goldstein NP
Mayo Clin Proc 1984 Jun;59(6):404-10. doi: 10.1016/s0025-6196(12)61464-5. PMID: 6727430
Ashwal S, Thrasher TV, Rice DR, Wenger DA
Ann Neurol 1984 Aug;16(2):184-92. doi: 10.1002/ana.410160205. PMID: 6089645

Diagnosis

Bronte Anaut M, Arredondo Montero J
Ann Pathol 2024 Mar;44(2):150-151. Epub 2023 Oct 19 doi: 10.1016/j.annpat.2023.10.001. PMID: 37865572
Newman B, Hu W, Nigro K, Gilliam AC
J Am Acad Dermatol 2007 Feb;56(2):302-16. Epub 2006 Oct 9 doi: 10.1016/j.jaad.2006.06.010. PMID: 17097374
Hirayama Y, Kohda K, Andoh M, Matsumoto S, Nakazawa O, Nobuoka A, Mochizuki C, Takayanagi N, Ezoe A
Intern Med 1996 May;35(5):419-21. doi: 10.2169/internalmedicine.35.419. PMID: 8797061
Karayalcin G, Rosner F, Sawitsky A
Lancet 1971 Aug 7;2(7719):318. doi: 10.1016/s0140-6736(71)91365-1. PMID: 4105006
Zlotnick A, Fried K
Lancet 1970 Oct 10;2(7676):776. doi: 10.1016/s0140-6736(70)90254-0. PMID: 4195998

Therapy

Michot JM, Gubavu C, Fourn E, Maigne G, Teicher E, Angoulvant A, Blanche S, Lortholary O, Coilly A, Duclos-Vallée JC, Sebagh M, Guettier C, Aumont C, Delfraissy JF, Lambotte O
Int J Antimicrob Agents 2014 Jun;43(6):566-9. Epub 2014 Apr 12 doi: 10.1016/j.ijantimicag.2014.02.015. PMID: 24787480
Bigorgne C, Le Tourneau A, Vahedi K, Rio B, Messing B, Molina T, Audouin J, Diebold J
Leuk Lymphoma 1998 Feb;28(5-6):523-9. doi: 10.3109/10428199809058360. PMID: 9613982
Meiklejohn DJ, Baden H, Greaves M
Clin Lab Haematol 1997 Sep;19(3):219-21. PMID: 9352150
Bigorgne C, Le Tourneau A, Messing B, Rio B, Giraud V, Molina T, Audouin J, Diebold J
Br J Haematol 1996 Nov;95(2):258-62. doi: 10.1046/j.1365-2141.1996.d01-1907.x. PMID: 8904878
Mowat AP
Eur J Pediatr 1992;151 Suppl 1:S32-8. doi: 10.1007/BF02125800. PMID: 1345101

Prognosis

Newman B, Hu W, Nigro K, Gilliam AC
J Am Acad Dermatol 2007 Feb;56(2):302-16. Epub 2006 Oct 9 doi: 10.1016/j.jaad.2006.06.010. PMID: 17097374
Candoni A, Grimaz S, Doretto P, Fanin R, Falcomer F, Bembi B
Ann Hematol 2001 Oct;80(10):620-2. doi: 10.1007/s002770100354. PMID: 11732877
Yamauchi K, Shimamura K
Eur Respir J 1995 Sep;8(9):1620-3. PMID: 8575594
Okano S, Takeuchi Y, Kohmura E, Yoshioka H, Sawada T
Pediatr Neurol 1992 Jan-Feb;8(1):72-4. doi: 10.1016/0887-8994(92)90058-7. PMID: 1532715

Clinical prediction guides

Faivre L, Saugier-Veber P, Pais de Barros JP, Verges B, Couret B, Lorcerie B, Thauvin C, Charbonnier F, Huet F, Gambert P, Frebourg T, Duvillard L
Eur J Hum Genet 2005 Nov;13(11):1186-91. doi: 10.1038/sj.ejhg.5201480. PMID: 16094309
Yamauchi K, Shimamura K
Eur Respir J 1995 Sep;8(9):1620-3. PMID: 8575594

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...