HLAS
MCID: HST017
MIFTS: 57

Histiocytosis-Lymphadenopathy Plus Syndrome (HLAS)

Categories: Ear diseases, Endocrine diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Histiocytosis-Lymphadenopathy Plus Syndrome

MalaCards integrated aliases for Histiocytosis-Lymphadenopathy Plus Syndrome:

Name: Histiocytosis-Lymphadenopathy Plus Syndrome 56 12 52 25 73 29 6
Histiocytosis with Joint Contractures and Sensorineural Deafness 56 12 52 73 13 71
H Syndrome 56 12 52 58 73 36
Faisalabad Histiocytosis 56 12 52 73
Hjcd 56 12 52 73
Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus 56 12 73
Sinus Histiocytosis and Massive Lymphadenopathy 56 12 73
Phid 56 12 73
Shml 56 12 73
Familial Rosai-Dorfman Disease 12 73
Slc29a3 Spectrum Disorder 52 25
Hyperpigmentation, Cutaneous, with Hypertrichosis, Hepatosplenomegaly, Heart Anomalies, and Hypogonadism with or Without Hearing Loss 56
Histiocytosis and Lymphadenopathy with or Without Cutaneous, Cardiac, and/or Endocrine Features, Joint Contractures, and/or Deafness 56
Cutaneous Hyperpigmentation with Hypertrichosis, Hepatosplenomegaly, Heart Anomalies, and Hypogonadism with or Without Hearing Loss 12
Histiocytosis and Lymphadenopathy with or Without Cutaneous, Cardiac, and/or Endocrine Features, Joint Contractures and/or Deafness 12
Cutaneous Hyperpigmentation with Hypertrichosis Hepatosplenomegaly Heart Anomalies and Hypogonadism with or Without Hearing Loss 73
Histiocytosis and Lymphadenopathy with or Without Cutaneous Cardiac and/or Endocrine Features Joint Contractures and/or Deafness 73
Pigmented Hypertrichosis with Insulin-Dependent Diabetes Mellitus; Phid 56
Histiocytosis with Joint Contractures and Sensorineural Deafness; Hjcd 56
Sinus Histiocytosis and Massive Lymphadenopathy; Shml 56
Syndrome, Histiocytosis-Lymphadenopathy Plus 39
Rosai-Dorfman Disease, Familial 56
Histiocytosis, Sinus 43
Slc29a3 Disorder 25
H Disease 54
Hlas 73

Characteristics:

Orphanet epidemiological data:

58
h syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: any age;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
very variable phenotype, with some patients having many features and others only a few


HPO:

31
histiocytosis-lymphadenopathy plus syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare otorhinolaryngological diseases
Rare skin diseases
Rare endocrine diseases


Summaries for Histiocytosis-Lymphadenopathy Plus Syndrome

Genetics Home Reference : 25 Histiocytosis-lymphadenopathy plus syndrome (also known as SLC29A3 spectrum disorder) is a group of conditions with overlapping signs and symptoms that affect many parts of the body. This group of disorders includes H syndrome, pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID), Faisalabad histiocytosis, and familial Rosai-Dorfman disease (also known as sinus histiocytosis with massive lymphadenopathy or SHML). These conditions were once thought to be distinct disorders; however, because of the overlapping features and shared genetic cause, they are now considered to be part of the same disease spectrum. While some affected individuals have signs and symptoms characteristic of one of the conditions, others have a range of features from two or more of the conditions. The pattern of signs and symptoms can vary even within the same family. SLC29A3 A feature common to the disorders in this spectrum is histiocytosis, which is the overgrowth of immune system cells called histiocytes. The cells abnormally accumulate in one or more tissues in the body, which can lead to organ or tissue damage. The buildup often occurs in the lymph nodes, leading to swelling of the lymph nodes (lymphadenopathy). Other areas of cell accumulation can include the skin, kidneys, brain and spinal cord (central nervous system), or digestive tract. This spectrum is known as histiocytosis-lymphadenopathy plus syndrome because the disorders that make up the spectrum can have additional signs and symptoms. A characteristic feature of H syndrome is abnormal patches of skin (lesions), typically on the lower body. These lesions are unusually dark (hyperpigmented) and have excessive hair growth (hypertrichosis). In addition, histiocytes accumulate at the site of the skin lesions. Other features of H syndrome include enlargement of the liver (hepatomegaly), heart abnormalities, hearing loss, reduced amounts of hormones that direct sexual development (hypogonadism), and short stature. Like H syndrome, PHID causes patches of hyperpigmented skin with hypertrichosis. PHID is also characterized by the development of type 1 diabetes (also known as insulin-dependent diabetes mellitus), which usually begins in childhood. Type 1 diabetes occurs when the body does not produce enough of the hormone insulin, leading to dysregulation of blood sugar levels. Faisalabad histiocytosis typically causes lymphadenopathy and swelling of the eyelids due to accumulation of histiocytes. Affected individuals can also have joint deformities called contractures in their fingers or toes and hearing loss. The most common feature of familial Rosai-Dorfman disease is lymphadenopathy, usually affecting lymph nodes in the neck. Histiocytes can also accumulate in other parts of the body.

MalaCards based summary : Histiocytosis-Lymphadenopathy Plus Syndrome, also known as histiocytosis with joint contractures and sensorineural deafness, is related to hydrops fetalis, nonimmune and alpha-thalassemia, and has symptoms including fever An important gene associated with Histiocytosis-Lymphadenopathy Plus Syndrome is SLC29A3 (Solute Carrier Family 29 Member 3), and among its related pathways/superpathways are Binding and Uptake of Ligands by Scavenger Receptors and Malaria. The drugs Immunologic Factors and Vaccines have been mentioned in the context of this disorder. Affiliated tissues include heart, lymph node and liver, and related phenotypes are delayed puberty and decreased testicular size

Disease Ontology : 12 A syndrome characterized by histiocytosis, hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, and reduced height that has material basis in homozygous or compound heterozygous mutation in SLC29A3 on 10q22.1. This syndrome comprises features from 4 histiocytic disorders that were previously considered distinct: Faisalabad histiocytosis, sinus histiocytosis with massive lymphadenopathy, H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome.

NIH Rare Diseases : 52 Histiocytosis-lymphadenopathy plus syndrome is a group of conditions with overlapping signs and symptoms that affect many parts of the body. This group of disorders includes H syndrome , pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID) , Faisalabad histiocytosis , and familial Rosai-Dorfman disease (also known as familial sinus histiocytosis with massive lymphadenopathy or FSHML). These conditions were once thought to be distinct disorders; however, because of the overlapping features and shared genetic cause, they are now considered to be part of the same disease spectrum. While some affected individuals have signs and symptoms characteristic of one of these conditions, others have a range of features from two or more of the conditions. The pattern of signs and symptoms can vary, even within the same family. All of the conditions in the spectrum are characterized by histiocytosis, which is an overgrowth of immune system cells called histiocytes. These cells abnormally accumulate in one or more tissues in the body, which can lead to organ or tissue damage. The lymph nodes are commonly affected, leading to swelling of the lymph nodes (lymphadenopathy ). Other areas of cell accumulation can include skin, kidneys, brain and spinal cord (central nervous system ), or digestive tract. The spectrum is known as histiocytosis-lymphadenoapthy plus syndrome because the disorders that make up the spectrum can have additional signs and symptoms. H syndrome is named for the collection of symptoms - all starting with the letter H - that are commonly present. These include hyperpigmented skin lesions with excessive hair growth (hypertrichosis ) and histiocyte accumulation, enlargement of the liver or liver and spleen (hepatomegaly or hepatosplenomegaly ), heart abnormalities, hearing loss , reduced amounts of hormones that direct sexual development (hypogonadism ), and short stature (reduced height). In some cases, hyperglycemia /diabetes mellitus may also be present. PHID is characterized by patches of hyperpigmented skin with hypertrichosis and the development of type 1 diabetes during childhood. Faisalabad histiocytosis is characterized by lymphadenopathy and swelling of the eyelids due to the accumulation of histiocytes. Affected individuals may also have joint deformities (contractures ) in their fingers or toes, and hearing loss. Familial Rosai-Dorfman disease is characterized by lymphadenopathy, most often in the neck. Histiocytes can also accumulate in other parts of the body. Histiocytosis-lymphadenopathy plus syndrome is caused by mutations in the SLC29A3 gene . The condition is inherited in an autosomal recessive pattern. Treatment is aimed at treating the symptoms present in each individual.

OMIM : 56 The histiocytosis-lymphadenopathy plus syndrome comprises features of 4 histiocytic disorders previously thought to be distinct: Faisalabad histiocytosis (FHC), sinus histiocytosis with massive lymphadenopathy (SHML), H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID). FHC described an autosomal recessive disease involving joint deformities, sensorineural hearing loss, and subsequent development of generalized lymphadenopathy and swellings in the eyelids that contain histiocytes (summary by Morgan et al., 2010). SHML, or familial Rosai-Dorfman disease, was described as a rare cause of lymph node enlargement in children, consisting of chronic massive enlargement of cervical lymph nodes frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Extranodal sites were involved in approximately 25% of patients, including salivary glands, orbit, eyelid, spleen, and testes. The involvement of retropharyngeal lymphoid tissue sometimes caused snoring and sleep apnea (summary by Kismet et al., 2005). H syndrome was characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism; hearing loss was also found in about half of patients, and many had short stature. PHID was characterized by predominantly antibody-negative insulin-dependent diabetes mellitus associated with pigmented hypertrichosis and variable occurrence of other features of H syndrome, with hepatosplenomegaly occurring in about half of patients (Cliffe et al., 2009). Bolze et al. (2012) noted that mutations in the SLC29A3 gene (612373) had been implicated in H syndrome, PHID, FHC, and SHML, and that some patients presented a combination of features from 2 or more of these syndromes, leading to the suggestion that these phenotypes should be grouped together as 'SLC29A3 disorder.' Bolze et al. (2012) suggested that the histologic features of the lesions seemed to be the most uniform phenotype in these patients. In addition, the immunophenotype of infiltrating cells in H syndrome patients was shown to be the same as that seen in patients with the familial form of Rosai-Dorfman disease, further supporting the relationship between these disorders (Avitan-Hersh et al., 2011; Colmenero et al., 2012). (602782)

KEGG : 36 The H syndrome is an autosomal-recessive condition characterized by the association of cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, sensorineural hearing loss, hypogonadism, short stature, and hyperglycemia. Anomalies such as hallux valgus and fixed flexion contractures of the toe and finger joints are additional clinical fiindings.

UniProtKB/Swiss-Prot : 73 Histiocytosis-lymphadenopathy plus syndrome: A syndrome characterized by the combination of features from 2 or more of four histiocytic disorders, originally thought to be distinct: Faisalabad histiocytosis (FHC), sinus histiocytosis with massive lymphadenopathy (SHML), H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID). FHC features include joint deformities, sensorineural hearing loss, and subsequent development of generalized lymphadenopathy and swellings in the eyelids that contain histiocytes. SHML causes lymph node enlargement in children frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. H syndrome is characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism; hearing loss is found in about half of patients. PHID is characterized by predominantly antibody-negative insulin-dependent diabetes mellitus associated with pigmented hypertrichosis and variable occurrence of other features of H syndrome.

Wikipedia : 74 H syndrome, also known as Histiocytosis-lymphadenopathy plus syndrome or PHID, is a rare genetic... more...

Related Diseases for Histiocytosis-Lymphadenopathy Plus Syndrome

Diseases related to Histiocytosis-Lymphadenopathy Plus Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 1911)
# Related Disease Score Top Affiliating Genes
1 hydrops fetalis, nonimmune 29.6 HBB HBA2
2 alpha-thalassemia 29.6 HBB HBA2 G6PD
3 hypochromic microcytic anemia 29.4 HBB HBA2
4 plasmodium falciparum malaria 29.4 HBB G6PD
5 thalassemia 29.3 HBB HBA2 G6PD
6 deficiency anemia 29.1 HBB HBA2 G6PD
7 sickle cell disease 29.0 HBB HBA2 G6PD
8 beta-thalassemia 29.0 HBB HBA2 G6PD
9 sickle cell anemia 28.9 HBB HBA2 G6PD
10 methemoglobinemia 28.9 HBB G6PD
11 microcytic anemia 28.8 HBB HBA2 G6PD
12 hemoglobin zurich 28.8 HBB HBA2
13 iron metabolism disease 28.7 HBB HBA2
14 malaria 28.7 HBB HBA2 G6PD
15 hemoglobinopathy 28.7 HBB HBA2 G6PD
16 polycythemia 28.6 HBB HBA2
17 hemolytic anemia 28.6 HBB HBA2 G6PD
18 glucosephosphate dehydrogenase deficiency 28.6 HBB G6PD
19 hereditary spherocytosis 28.5 HBB G6PD
20 acute chest syndrome 28.5 HBB G6PD
21 hereditary elliptocytosis 28.5 HBB G6PD
22 hemoglobin h disease 28.0 HBB HBA2 G6PD
23 anti-hla hyperimmunization 12.4
24 immunodeficiency, partial combined, with absence of hla determinants and beta-2-microglobulin from lymphocytes 12.3
25 t-cell subgroups, non-hla-linked 12.3
26 hla modifier 12.3
27 bare lymphocyte syndrome, type i 12.2
28 bare lymphocyte syndrome, type ii 12.1
29 alpha-thalassemia myelodysplasia syndrome 11.8
30 graft-versus-host disease 11.8
31 rheumatoid arthritis 11.7
32 celiac disease 1 11.7
33 severe cutaneous adverse reaction 11.6
34 dermatitis herpetiformis 11.6
35 temporal arteritis 11.6
36 panbronchiolitis, diffuse 11.5
37 spondyloarthropathy 1 11.5
38 graves' disease 11.5
39 stevens-johnson syndrome/toxic epidermal necrolysis 11.5
40 combined t cell and b cell immunodeficiency 11.5
41 narcolepsy 11.5
42 hashimoto thyroiditis 11.4
43 psoriasis 1 11.4
44 behcet syndrome 11.4
45 sjogren syndrome 11.4
46 diabetes mellitus, ketosis-prone 11.4
47 narcolepsy 1 11.4
48 cutaneous lupus erythematosus 11.4
49 goodpasture syndrome 11.4
50 adult-onset still's disease 11.4

Graphical network of the top 20 diseases related to Histiocytosis-Lymphadenopathy Plus Syndrome:



Diseases related to Histiocytosis-Lymphadenopathy Plus Syndrome

Symptoms & Phenotypes for Histiocytosis-Lymphadenopathy Plus Syndrome

Human phenotypes related to Histiocytosis-Lymphadenopathy Plus Syndrome:

58 31 (show top 50) (show all 69)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 delayed puberty 58 31 hallmark (90%) Very frequent (99-80%) HP:0000823
2 decreased testicular size 58 31 hallmark (90%) Very frequent (99-80%) HP:0008734
3 hyperpigmentation of the skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0000953
4 stiff skin 58 31 hallmark (90%) Very frequent (99-80%) HP:0030053
5 scleroderma 58 31 hallmark (90%) Very frequent (99-80%) HP:0100324
6 histiocytosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0100727
7 hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000365
8 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
9 lymphadenopathy 58 31 frequent (33%) Frequent (79-30%) HP:0002716
10 hepatosplenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001433
11 hypertrichosis 58 31 frequent (33%) Frequent (79-30%) HP:0000998
12 camptodactyly 58 31 frequent (33%) Frequent (79-30%) HP:0012385
13 hyperreflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001347
14 hydrocephalus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000238
15 diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000819
16 delayed skeletal maturation 58 31 occasional (7.5%) Occasional (29-5%) HP:0002750
17 gingival overgrowth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000212
18 pes planus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001763
19 malabsorption 58 31 occasional (7.5%) Occasional (29-5%) HP:0002024
20 alopecia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001596
21 hallux valgus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001822
22 ichthyosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0008064
23 intellectual disability, mild 58 31 occasional (7.5%) Occasional (29-5%) HP:0001256
24 full cheeks 58 31 occasional (7.5%) Occasional (29-5%) HP:0000293
25 hypertriglyceridemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002155
26 psoriasiform dermatitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0003765
27 hernia 58 31 occasional (7.5%) Occasional (29-5%) HP:0100790
28 osteolysis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002797
29 microcytic anemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001935
30 lipodystrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0009125
31 hypogonadism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000135
32 micropenis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000054
33 proptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000520
34 cleft upper lip 58 31 occasional (7.5%) Occasional (29-5%) HP:0000204
35 varicose veins 58 31 occasional (7.5%) Occasional (29-5%) HP:0002619
36 azoospermia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000027
37 recurrent fractures 58 31 occasional (7.5%) Occasional (29-5%) HP:0002757
38 recurrent pharyngitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0100776
39 gynecomastia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000771
40 enlarged kidney 58 31 occasional (7.5%) Occasional (29-5%) HP:0000105
41 bronchiectasis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002110
42 amenorrhea 58 31 occasional (7.5%) Occasional (29-5%) HP:0000141
43 corneal arcus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001084
44 chronic rhinitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002257
45 facial telangiectasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0007380
46 upper eyelid edema 58 31 occasional (7.5%) Occasional (29-5%) HP:0012724
47 ventricular septal defect 31 occasional (7.5%) HP:0001629
48 cardiomegaly 31 occasional (7.5%) HP:0001640
49 atrial septal defect 31 occasional (7.5%) HP:0001631
50 mitral valve prolapse 31 occasional (7.5%) HP:0001634

Symptoms via clinical synopsis from OMIM:

56
Skeletal Hands:
clinodactyly
camptodactyly
contractures of fingers

Abdomen Liver:
hepatomegaly

Skeletal Feet:
hallux valgus
contractures of toes

Endocrine Features:
hypergonadotropic hypogonadism
growth hormone deficiency
hypogonadotropic hypogonadism (rare)
diabetes mellitus, insulin-dependent

Head And Neck Neck:
cervical lymphadenopathy

Head And Neck Ears:
hearing loss, sensorineural

Head And Neck Face:
submandibular lymphadenopathy

Head And Neck Mouth:
retropharyngeal lymphadenopathy

Skeletal:
intrauterine fractures of long bones and clavicles

Muscle Soft Tissue:
retroperitoneal fibrosis (rare)

Immunology:
hyperglobulinemia, polyclonal (in some patients)
lymphadenopathy, generalized (in some patients)

Abdomen Spleen:
splenomegaly

Growth Height:
short stature

Metabolic Features:
fever

Head And Neck Eyes:
episcleritis
exophthalmos
histiocytic deposits in eyelids
eyelid infiltrates
orbital mass due to histiocytosis

Cardiovascular Heart:
ventricular septal defect (rare)
atrial septal defect (rare)
septal thickening (rare)
mitral valve prolapse (rare)
cardiomegaly (rare)
more
Abdomen Pancreas:
diabetes mellitus, insulin-dependent
pancreatic exocrine deficiency
pancreatomegaly (rare)
pancreatic hypoplasia, mild (rare)

Head And Neck Nose:
nasal mass due to histiocytosis

Abdomen External Features:
inguinal lymphadenopathy, bilateral, extending across suprapubic area

Skeletal Limbs:
contractures of elbows

Hematology:
nonclonal myeloproliferation

Laboratory Abnormalities:
elevated inflammatory markers

Clinical features from OMIM:

602782

UMLS symptoms related to Histiocytosis-Lymphadenopathy Plus Syndrome:


fever

GenomeRNAi Phenotypes related to Histiocytosis-Lymphadenopathy Plus Syndrome according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-181 9.1 HBA2 SLC29A3
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-184 9.1 SLC29A3
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.1 SLC29A3
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.1 HBA2
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 9.1 HBA2

Drugs & Therapeutics for Histiocytosis-Lymphadenopathy Plus Syndrome

Drugs for Histiocytosis-Lymphadenopathy Plus Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Immunologic Factors Phase 4
2 Vaccines Phase 4
3 Heptavalent Pneumococcal Conjugate Vaccine Phase 4
4 Aluminum phosphate Phase 4
5
tannic acid Approved Phase 3 1401-55-4
6
Benzocaine Approved, Investigational Phase 3 1994-09-7, 94-09-7 2337
7 Immunoglobulin G Phase 3
8 Pharmaceutical Solutions Phase 3
9 Antibodies Phase 3
10 Rho(D) Immune Globulin Phase 3
11 Immunoglobulins Phase 3
12 Immunoglobulins, Intravenous Phase 3
13 gamma-Globulins Phase 3
14
nivolumab Approved Phase 2 946414-94-4
15 Antineoplastic Agents, Immunological Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Randomised Controlled Trial of Pneumococcal Conjugate Vaccines Synflorix and Prevenar13 in Sequence or Alone in High-risk Indigenous Infants (PREV-IX_COMBO): Immunogenicity, Carriage and Otitis Media Outcomes Completed NCT01174849 Phase 4 Synflorix;Prevenar13;COMBO
2 Pneumococcal Conjugate Vaccine (PCV) Schedules for the Northern Territory (NT): Randomised Controlled Trial of Booster Vaccines to Broaden and Strengthen Protection From Invasive and Mucosal Infections. Active, not recruiting NCT01735084 Phase 4
3 An Open-Label, Single-Arm, Historically Controlled, Prospective, Multicenter Phase III Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Immune Globulin Intravenous (Human) GC5107 in Subjects With Primary Humoral Immunodeficiency Unknown status NCT02783482 Phase 3
4 An Alternative Booster Vaccine Against Meningitis and Ear Infections. Completed NCT01443416 Phase 3
5 Phase III Study of Immune Globulin Intravenous (Human) IGIV-SN in Pediatric Subjects With Primary Humoral Immunodeficiency Not yet recruiting NCT03492710 Phase 3
6 A Phase 2 Study to Assess the Safety and Efficacy of Cobimetinib in Refractory Langerhans Cell Histiocytosis, LCH-Associated Neurodegenerative Disease, and Other Histiocytic Disorders. Not yet recruiting NCT04079179 Phase 2 Cobimetinib
7 Phase II Trial of VB-111 in Combination With Nivolumab in Patients With Metastatic Colorectal Cancer (mCRC) Not yet recruiting NCT04166383 Phase 2 Nivolumab
8 Impact of Introduction of PHiD-CV (Pneumococcal Nontypeable H. Influenza Protein D-conjugate Vaccine) for Nunavik Children, Quebec, Canada Unknown status NCT01694329
9 International Rare Histiocytic Disorders Registry (IRHDR) Recruiting NCT02285582
10 Determination of the Oxygen Dissociation Curve Under the Conditions of an Avalanche Burial With an Air Pocket Not yet recruiting NCT04041531

Search NIH Clinical Center for Histiocytosis-Lymphadenopathy Plus Syndrome

Cochrane evidence based reviews: histiocytosis, sinus

Genetic Tests for Histiocytosis-Lymphadenopathy Plus Syndrome

Genetic tests related to Histiocytosis-Lymphadenopathy Plus Syndrome:

# Genetic test Affiliating Genes
1 Histiocytosis-Lymphadenopathy Plus Syndrome 29 SLC29A3

Anatomical Context for Histiocytosis-Lymphadenopathy Plus Syndrome

MalaCards organs/tissues related to Histiocytosis-Lymphadenopathy Plus Syndrome:

40
Heart, Lymph Node, Liver, T Cells, Kidney, Skin, Thyroid

Publications for Histiocytosis-Lymphadenopathy Plus Syndrome

Articles related to Histiocytosis-Lymphadenopathy Plus Syndrome:

(show all 32)
# Title Authors PMID Year
1
Whole-exome sequencing identifies mutations in the nucleoside transporter gene SLC29A3 in dysosteosclerosis, a form of osteopetrosis. 61 56 6
22875837 2012
2
A mild form of SLC29A3 disorder: a frameshift deletion leads to the paradoxical translation of an otherwise noncoding mRNA splice variant. 56 6
22238637 2012
3
Progressive hearing loss associated with a unique cervical node due to a homozygous SLC29A3 mutation: a very mild phenotype. 56 6
21888995 2012
4
Identification of two novel mutations in SLC29A3 encoding an equilibrative nucleoside transporter (hENT3) in two distinct Syrian families with H syndrome: expression studies of SLC29A3 (hENT3) in human skin. 56 6
22653152 2012
5
A case of H syndrome showing immunophenotye similarities to Rosai-Dorfman disease. 56 6
21178579 2011
6
Expanding the clinical spectrum of SLC29A3 gene defects. 56 6
20619369 2010
7
Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease. 56 6
20140240 2010
8
The H syndrome: two novel mutations affecting the same amino acid residue of hENT3. 56 6
19889517 2010
9
SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway. 56 6
19336477 2009
10
Diabetes mellitus, exocrine pancreatic deficiency, hypertrichosis, hyperpigmentation, and chronic inflammation: confirmation of a syndrome. 56 6
19175903 2009
11
Rhinoscleroma: a French national retrospective study of epidemiological and clinical features. 56 6
18947330 2008
12
The H syndrome is caused by mutations in the nucleoside transporter hENT3. 56 6
18940313 2008
13
Pigmented hypertrichotic dermatosis and insulin dependent diabetes: manifestations of a unique genetic disorder? 56 6
17461801 2007
14
Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness. 56 6
16155931 2006
15
POEMS in childhood. 56 6
16650224 2006
16
Sinus histiocytosis with massive lymphadenopathy in three brothers. 56 6
16118898 2005
17
Autozygosity mapping, to chromosome 11q25, of a rare autosomal recessive syndrome causing histiocytosis, joint contractures, and sensorineural deafness. 56 6
9545394 1998
18
Mutation in the SLC29A3 gene: a new cause of a monogenic, autoinflammatory condition. 6
23530176 2013
19
Emperipolesis: an additional common histopathologic finding in H syndrome and Rosai-Dorfman disease. 56
22356918 2012
20
Human equilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impair nucleoside transport, protein localization, and stability. 6
20595384 2010
21
The H syndrome: a genodermatosis characterized by indurated, hyperpigmented, and hypertrichotic skin with systemic manifestations. 56
18410979 2008
22
Autosomal recessive plasma cell panniculitis with morphea-like clinical manifestation. 56
16631937 2006
23
Histiocytes and histiocytosis. 56
7524755 1994
24
Tocilizumab for the Treatment of SLC29A3 Mutation Positive PHID Syndrome. 61
29079714 2017
25
Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome is associated with severe chronic inflammation and cardiomyopathy, and represents a new monogenic autoinflammatory syndrome. 61
23729543 2013
26
PIP4KIIA and beta-globin: transcripts differentially expressed in reticulocytes and associated with high levels of Hb H in two siblings with Hb H disease. 54
19656170 2009
27
A laboratory strategy for genotyping haemoglobin H disease in the Chinese. 54
17018682 2007
28
Universal newborn screening for Hb H disease in California. 54
11551109 2001
29
Phenotypic and molecular diversity of haemoglobin H disease: a Greek experience. 54
11122156 2000
30
HB H disease with homozygosity for red cell G6PD deficiency in a Turkish female. 54
9576333 1998
31
Capillary isoelectric focusing of hemoglobin variants in the pediatric clinical laboratory. 54
9372271 1997
32
Hb Seal Rock [(alpha 2)142 term-->Glu, codon 142 TAA-->GAA]: an extended alpha chain variant associated with anemia, microcytosis, and alpha-thalassemia-2 (-3.7 Kb). 54
9255612 1997

Variations for Histiocytosis-Lymphadenopathy Plus Syndrome

ClinVar genetic disease variations for Histiocytosis-Lymphadenopathy Plus Syndrome:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SLC29A3 NM_018344.6(SLC29A3):c.1309G>A (p.Gly437Arg)SNV Pathogenic 565 rs121912584 10:73122246-73122246 10:71362489-71362489
2 SLC29A3 NM_018344.6(SLC29A3):c.1045del (p.Leu349fs)deletion Pathogenic 566 rs869025176 10:73121978-73121978 10:71362221-71362221
3 SLC29A3 NM_018344.6(SLC29A3):c.940del (p.Tyr314fs)deletion Pathogenic 567 rs869025177 10:73121877-73121877 10:71362120-71362120
4 SLC29A3 NM_018344.6(SLC29A3):c.347T>G (p.Met116Arg)SNV Pathogenic 568 rs267607057 10:73104012-73104012 10:71344255-71344255
5 SLC29A3 NM_018344.6(SLC29A3):c.1346C>G (p.Thr449Arg)SNV Pathogenic 569 rs267607058 10:73122283-73122283 10:71362526-71362526
6 SLC29A3 SLC29A3, IVS2, G-A, +1SNV Pathogenic 30946
7 SLC29A3 NM_018344.6(SLC29A3):c.308_309del (p.Tyr102_Phe103insTer)deletion Pathogenic 30947 rs796052139 10:73103972-73103973 10:71344215-71344216
8 SLC29A3 NM_018344.6(SLC29A3):c.1088G>A (p.Arg363Gln)SNV Pathogenic 30948 rs387907066 10:73122025-73122025 10:71362268-71362268
9 SLC29A3 NM_018344.6(SLC29A3):c.1279G>A (p.Gly427Ser)SNV Pathogenic 563 rs121912583 10:73122216-73122216 10:71362459-71362459
10 SLC29A3 NM_018344.6(SLC29A3):c.1157G>A (p.Arg386Gln)SNV Pathogenic 39870 rs397515429 10:73122094-73122094 10:71362337-71362337
11 SLC29A3 NM_018344.6(SLC29A3):c.607T>C (p.Ser203Pro)SNV Pathogenic 39871 rs397514626 10:73111542-73111542 10:71351785-71351785
12 SLC29A3 NM_018344.6(SLC29A3):c.1228C>T (p.Gln410Ter)SNV Pathogenic 130338 rs587780462 10:73122165-73122165 10:71362408-71362408
13 SLC29A3 NM_018344.6(SLC29A3):c.300+1G>ASNV Pathogenic 130339 rs587780463 10:73082812-73082812 10:71323055-71323055
14 SLC29A3 NM_018344.6(SLC29A3):c.479G>A (p.Trp160Ter)SNV Pathogenic 573984 rs776960135 10:73111414-73111414 10:71351657-71351657
15 SLC29A3 NM_018344.6(SLC29A3):c.243del (p.Lys81fs)deletion Pathogenic 636986 10:73082752-73082752 10:71322995-71322995
16 SLC29A3 NM_018344.6(SLC29A3):c.984del (p.Asn329fs)deletion Likely pathogenic 664261 10:73121920-73121920 10:71362163-71362163
17 SLC29A3 NM_018344.6(SLC29A3):c.611-1G>TSNV Likely pathogenic 659679 10:73115837-73115837 10:71356080-71356080
18 SLC29A3 NM_018344.6(SLC29A3):c.473C>T (p.Ser158Phe)SNV drug response 130341 rs780668 10:73111408-73111408 10:71351651-71351651
19 SLC29A3 NM_018344.6(SLC29A3):c.1330G>T (p.Glu444Ter)SNV Likely pathogenic 564 rs267607056 10:73122267-73122267 10:71362510-71362510
20 SLC29A3 NM_018344.6(SLC29A3):c.1146C>T (p.Phe382=)SNV Conflicting interpretations of pathogenicity 198230 rs148092033 10:73122083-73122083 10:71362326-71362326
21 SLC29A3 NM_018344.6(SLC29A3):c.73C>T (p.Arg25Ter)SNV Conflicting interpretations of pathogenicity 212200 rs746408350 10:73082584-73082584 10:71322827-71322827
22 SLC29A3 NM_018344.6(SLC29A3):c.1087C>T (p.Arg363Trp)SNV Conflicting interpretations of pathogenicity 30949 rs387907067 10:73122024-73122024 10:71362267-71362267
23 SLC29A3 NM_018344.6(SLC29A3):c.855G>A (p.Ser285=)SNV Conflicting interpretations of pathogenicity 300365 rs566110994 10:73121792-73121792 10:71362035-71362035
24 SLC29A3 NM_018344.6(SLC29A3):c.1001A>G (p.Asn334Ser)SNV Conflicting interpretations of pathogenicity 300368 rs144665176 10:73121938-73121938 10:71362181-71362181
25 SLC29A3 NM_018344.6(SLC29A3):c.714_715inv (p.Val239Ile)inversion Conflicting interpretations of pathogenicity 300363 10:73115941-73115942 10:71356184-71356185
26 SLC29A3 NM_018344.6(SLC29A3):c.1202G>A (p.Arg401His)SNV Uncertain significance 300370 rs199861210 10:73122139-73122139 10:71362382-71362382
27 SLC29A3 NM_018344.6(SLC29A3):c.*11A>CSNV Uncertain significance 300371 rs776790087 10:73122376-73122376 10:71362619-71362619
28 SLC29A3 NM_018344.6(SLC29A3):c.*85G>ASNV Uncertain significance 300372 rs115915981 10:73122450-73122450 10:71362693-71362693
29 SLC29A3 NM_018344.6(SLC29A3):c.*353C>ASNV Uncertain significance 300377 rs886047117 10:73122718-73122718 10:71362961-71362961
30 SLC29A3 NM_018344.6(SLC29A3):c.*429C>TSNV Uncertain significance 300379 rs140867523 10:73122794-73122794 10:71363037-71363037
31 SLC29A3 NM_018344.6(SLC29A3):c.*603A>GSNV Uncertain significance 300382 rs886047120 10:73122968-73122968 10:71363211-71363211
32 SLC29A3 NM_018344.6(SLC29A3):c.*705G>ASNV Uncertain significance 300384 rs113080025 10:73123070-73123070 10:71363313-71363313
33 SLC29A3 NM_018344.6(SLC29A3):c.946T>G (p.Phe316Val)SNV Uncertain significance 300367 rs139066012 10:73121883-73121883 10:71362126-71362126
34 SLC29A3 NM_018344.6(SLC29A3):c.920G>A (p.Ser307Asn)SNV Uncertain significance 300366 rs556688985 10:73121857-73121857 10:71362100-71362100
35 SLC29A3 NM_018344.6(SLC29A3):c.*403C>TSNV Uncertain significance 300378 rs376297355 10:73122768-73122768 10:71363011-71363011
36 SLC29A3 NM_018344.6(SLC29A3):c.385G>A (p.Val129Ile)SNV Uncertain significance 300359 rs768974539 10:73111320-73111320 10:71351563-71351563
37 SLC29A3 NM_018344.6(SLC29A3):c.688G>A (p.Ala230Thr)SNV Uncertain significance 300362 rs147701543 10:73115915-73115915 10:71356158-71356158
38 SLC29A3 NM_018344.6(SLC29A3):c.862T>A (p.Ser288Thr)SNV Uncertain significance 566799 rs368747183 10:73121799-73121799 10:71362042-71362042
39 SLC29A3 NM_018344.6(SLC29A3):c.1219G>A (p.Val407Met)SNV Uncertain significance 572794 rs144517514 10:73122156-73122156 10:71362399-71362399
40 SLC29A3 NC_000010.10:g.(?_73079047)_(73082831_?)dupduplication Uncertain significance 583783 10:73079047-73082831 10:71319290-71323074
41 SLC29A3 NM_018344.6(SLC29A3):c.365A>G (p.Asn122Ser)SNV Uncertain significance 595707 rs772599816 10:73104030-73104030 10:71344273-71344273
42 SLC29A3 NM_018344.6(SLC29A3):c.*318C>TSNV Uncertain significance 300376 rs527551448 10:73122683-73122683 10:71362926-71362926
43 SLC29A3 NM_018344.6(SLC29A3):c.*657dupduplication Uncertain significance 300383 rs564371527 10:73123015-73123016 10:71363258-71363259
44 SLC29A3 NM_018344.6(SLC29A3):c.1147G>A (p.Val383Met)SNV Uncertain significance 468350 rs200001297 10:73122084-73122084 10:71362327-71362327
45 SLC29A3 NM_018344.6(SLC29A3):c.40A>G (p.Asn14Asp)SNV Uncertain significance 536248 rs541461094 10:73082551-73082551 10:71322794-71322794
46 SLC29A3 NM_018344.6(SLC29A3):c.986A>G (p.Asn329Ser)SNV Uncertain significance 536247 rs1554818046 10:73121923-73121923 10:71362166-71362166
47 SLC29A3 NM_018344.6(SLC29A3):c.148T>C (p.Phe50Leu)SNV Uncertain significance 536249 rs769621228 10:73082659-73082659 10:71322902-71322902
48 SLC29A3 NM_018344.6(SLC29A3):c.516G>A (p.Met172Ile)SNV Uncertain significance 536251 rs1554817114 10:73111451-73111451 10:71351694-71351694
49 SLC29A3 NM_018344.6(SLC29A3):c.68G>A (p.Ser23Asn)SNV Uncertain significance 571603 rs146423891 10:73082579-73082579 10:71322822-71322822
50 SLC29A3 NM_018344.6(SLC29A3):c.146G>C (p.Arg49Pro)SNV Uncertain significance 567196 rs201610819 10:73082657-73082657 10:71322900-71322900

UniProtKB/Swiss-Prot genetic disease variations for Histiocytosis-Lymphadenopathy Plus Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 SLC29A3 p.Gly427Ser VAR_057884 rs121912583
2 SLC29A3 p.Gly437Arg VAR_057885 rs121912584
3 SLC29A3 p.Met116Arg VAR_067801 rs267607057
4 SLC29A3 p.Arg134Cys VAR_067802 rs143055760
5 SLC29A3 p.Ser184Arg VAR_067804 rs102325701
6 SLC29A3 p.Arg363Gln VAR_067806 rs387907066
7 SLC29A3 p.Arg363Trp VAR_067807 rs387907067
8 SLC29A3 p.Thr449Arg VAR_067809 rs267607058

Expression for Histiocytosis-Lymphadenopathy Plus Syndrome

Search GEO for disease gene expression data for Histiocytosis-Lymphadenopathy Plus Syndrome.

Pathways for Histiocytosis-Lymphadenopathy Plus Syndrome

GO Terms for Histiocytosis-Lymphadenopathy Plus Syndrome

Cellular components related to Histiocytosis-Lymphadenopathy Plus Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 blood microparticle GO:0072562 9.26 HBB HBA2
2 endocytic vesicle lumen GO:0071682 9.16 HBB HBA2
3 hemoglobin complex GO:0005833 8.96 HBB HBA2
4 haptoglobin-hemoglobin complex GO:0031838 8.62 HBB HBA2

Biological processes related to Histiocytosis-Lymphadenopathy Plus Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 receptor-mediated endocytosis GO:0006898 9.4 HBB HBA2
2 cellular oxidant detoxification GO:0098869 9.37 HBB HBA2
3 response to hydrogen peroxide GO:0042542 9.32 HBB HBA2
4 positive regulation of cell death GO:0010942 9.26 HBB HBA2
5 bicarbonate transport GO:0015701 9.16 HBB HBA2
6 hydrogen peroxide catabolic process GO:0042744 8.96 HBB HBA2
7 oxygen transport GO:0015671 8.62 HBB HBA2

Molecular functions related to Histiocytosis-Lymphadenopathy Plus Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 heme binding GO:0020037 9.37 HBB HBA2
2 peroxidase activity GO:0004601 9.32 HBB HBA2
3 oxygen binding GO:0019825 9.26 HBB HBA2
4 oxygen carrier activity GO:0005344 9.16 HBB HBA2
5 organic acid binding GO:0043177 8.96 HBB HBA2
6 haptoglobin binding GO:0031720 8.62 HBB HBA2

Sources for Histiocytosis-Lymphadenopathy Plus Syndrome

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