Hermansky-Pudlak syndrome with neutropenia

General Information (adopted from Orphanet):

Synonyms, Signs: HPS2
Hermansky-Pudlak syndrome type 2
Number of Symptoms 45
OrphanetNr: 183678
OMIM Id: 608233
ICD-10: E70.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 8 cases [Orphanet]
Inheritance: Autosomal recessive
25117010 [IBIS]
Age of onset: Congenital onset
[Omim]

Disease classification (adopted from Orphanet):

Parent Diseases: Constitutional neutropenia with extra-haematopoietic manifestations
 -Rare genetic disease
 -Rare immune disease
Hermansky-Pudlak syndrome
 -Rare eye disease
 -Rare genetic disease
 -Rare hematologic disease
 -Rare skin disease
Immunodeficiency syndrome with hypopigmentation
 -Rare genetic disease
 -Rare immune disease
Unclassified primitive or secondary maculopathy
 -Rare eye disease
 -Rare genetic disease

Comment:

Hermansky-Pudlak syndrome type 2 (HPS2) is a sub-type of Hermansky-Pudlak syndrome and is characterized by neutropenia and immunodeficiency (PMID:25117010). HPS2 is caused by mutations in the gene AP3B1 encoding the adaptor-related protein complex 3, beta 1 subunit. AP3B1 is involved in organelle biogenesis associated with melanosomes, platelet dense granules, and lysosomes (PMID:27345985).

Symptom Information: Sort by abundance 

1
 (HPO:0011869) Abnormal platelet function Very frequent [IBIS] 12 / 7739
2
 (HPO:0002721) Immunodeficiency Frequent [IBIS] 25117010 IBIS 97 / 7739
3
 (HPO:0000252) Microcephaly 832 / 7739
4
 (HPO:0000670) Carious teeth 145 / 7739
5
 (HPO:0000319) Smooth philtrum 72 / 7739
6
 (HPO:0000343) Long philtrum 262 / 7739
7
 (HPO:0000280) Coarse facial features 189 / 7739
8
 (HPO:0000219) Thin upper lip vermilion 112 / 7739
9
 (HPO:0000704) Periodontitis 24 / 7739
10
 (HPO:0000431) Wide nasal bridge 290 / 7739
11
 (HPO:0000582) Upslanted palpebral fissure 185 / 7739
12
 (HPO:0007663) Reduced visual acuity 100 / 7739
13
 (HPO:0000486) Strabismus 576 / 7739
14
 (HPO:0000505) Visual impairment 297 / 7739
15
 (HPO:0001107) Ocular albinism 40 / 7739
16
 (HPO:0000639) Nystagmus 555 / 7739
17
 (HPO:0000613) Photophobia 158 / 7739
18
 (HPO:0000358) Posteriorly rotated ears 163 / 7739
19
 (HPO:0000369) Low-set ears 372 / 7739
20
 (HPO:0001270) Motor delay 322 / 7739
21
 (HPO:0001256) Intellectual disability, mild 141 / 7739
22
 (HPO:0001385) Hip dysplasia 242 / 7739
23
 (HPO:0008807) Acetabular dysplasia 6 / 7739
24
 (HPO:0001744) Splenomegaly 337 / 7739
25
 (HPO:0002240) Hepatomegaly 467 / 7739
26
 (HPO:0001022) Albinism 43 / 7739
27
 (HPO:0002286) Fair hair 20 / 7739
28
 (HPO:0007513) Generalized hypopigmentation 12 / 7739
29
 (HPO:0007384) Aberrant melanosome maturation 4 / 7739
30
 (HPO:0001873) Thrombocytopenia 224 / 7739
31
 (HPO:0001875) Neutropenia Very frequent [IBIS] 25117010 IBIS 83 / 7739
32
 (HPO:0002206) Pulmonary fibrosis 51 / 7739
33
 (HPO:0002718) Recurrent bacterial infections 75 / 7739
34
 (OMIM) Cutaneous albinism, tyrosinase-positive 1 / 7739
35
 (OMIM) Long, flat philtrum 5 / 7739
36
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
37
 (OMIM) Protruding midface 1 / 7739
38
 (OMIM) Decreased numbers of natural killer cells (NK) 1 / 7739
39
 (OMIM) Neutrophils show disorganized lysosomal compartments on ultrastructural analysis 1 / 7739
40
 (OMIM) Dental decay due to recurrent bacterial periodontitis 1 / 7739
41
 (OMIM) Pulmonary fibrosis due to recurrent infections 1 / 7739
42
 (HPO:0003577) Congenital onset 133 / 7739
43
 (OMIM) Absence of platelet dense bodies 1 / 7739
44
 (OMIM) Motor retardation, mild 1 / 7739
45
 (OMIM) Ocular albinism, tyrosinase-positive 1 / 7739

Associated genes:

AP3B1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by platelet defects and oculocutaneous albinism. HPS2 differs from the other forms of HPS in that it includes immunodeficiency in its phenotype, and patients with HPS2 have an ...
Clinical Description OMIM Kotzot et al. (1994) reported a boy and girl with tyrosinase (TYR; 606933)-positive oculocutaneous albinism, recurrent bacterial infections, granulocytopenia, intermittent thrombocytopenia, microcephaly, protruding midface, rough and projecting hair, and mild mental retardation. The patients were first cousins born ...
Molecular genetics OMIM Dell'Angelica et al. (1999) identified mutations in the AP3B1 gene (603401.0001-603401.0002) in 2 brothers with HPS2.

In a patient with a severe form of HPS2, Huizing et al. (2002) identified compound heterozygosity for 2 nonsense mutations ...