Reticular dysgenesis

General Information (adopted from Orphanet):

Synonyms, Signs: Generalized hematopoietic hypoplasia
severe combined immunodeficiency with leukopenia
Hematopoietic hypoplasia, generalized
SCID with leukopenia
AK2 deficiency
Reticular dysgenesia
Aleukocytosis
Congenital aleukocytosis
Congenital aleukia
de vaal disease
Number of Symptoms 48
OrphanetNr: 33355
OMIM Id: 267500
ICD-10: D81.0
UMLs: C0272167
C1282908
MeSH: C538361
MedDRA:
Snomed: 111584000
350353007

Prevalence, inheritance and age of onset:

Prevalence: 52 cases - PMID: 28331055 [IBIS]
Inheritance: Autosomal recessive
- PMID: 19043417 [IBIS]
Age of onset: Neonatal
Infancy
- PMID: 19043417 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
T-B- severe combined immunodeficiency
 -Rare genetic disease
 -Rare immune disease

Symptom Information: Sort by abundance 

1
 (HPO:0003270) Abdominal distention 535190 IBIS 46 / 7739
2
 (HPO:0002014) Diarrhea Very frequent [Orphanet] 956962; 28331055; 535190 IBIS 225 / 7739
3
 (HPO:0002013) Vomiting 535190 IBIS 191 / 7739
4
 (HPO:0002098) Respiratory distress 956962 IBIS 75 / 7739
5
 (HPO:0002205) Recurrent respiratory infections Very frequent [Orphanet] 28331055 IBIS 254 / 7739
6
 (HPO:0001518) Small for gestational age 28331055 IBIS 107 / 7739
7
 (HPO:0005561) Abnormality of bone marrow cell morphology 13840590; 28331055 IBIS 11 / 7739
8
 (HPO:0100827) Lymphocytosis 28331055 IBIS 5 / 7739
9
 (HPO:0001888) Lymphopenia 19043417; 956962; 28331055; 535190 IBIS 43 / 7739
10
 (HPO:0005528) Bone marrow hypocellularity 535190 IBIS 31 / 7739
11
 (HPO:0001662) Bradycardia 956962 IBIS 41 / 7739
12
 (HPO:0003287) Abnormality of mitochondrial metabolism Very frequent [Orphanet] 19043417 IBIS 12 / 7739
13
 (HPO:0008151) Prolonged prothrombin time 13840590 IBIS 13 / 7739
14
 (HPO:0010701) Abnormal immunoglobulin level Very frequent [Orphanet] 28331055 IBIS 49 / 7739
15
 (HPO:0002721) Immunodeficiency 19043417 IBIS 97 / 7739
16
 (HPO:0004430) Severe combined immunodeficiency Very frequent [Orphanet] 19043417; 28331055 IBIS 16 / 7739
17
 (HPO:0002719) Recurrent infections 19043416 IBIS 107 / 7739
18
 (HPO:0045071) Decrease in T cell number 28331055 IBIS 2 / 7739
19
 (HPO:0005354) Absent cellular immunity 28331055 IBIS 2 / 7739
20
 (HPO:0100806) Sepsis Very frequent [Orphanet] 956962; 13840590; 28331055 IBIS 48 / 7739
21
 (HPO:0001913) Granulocytopenia 19043417 IBIS 5 / 7739
22
 (HPO:0012234) Agranulocytosis 28331055 IBIS 4 / 7739
23
 (HPO:0005541) Congenital agranulocytosis 28331055 IBIS 2 / 7739
24
 (HPO:0001882) Leukopenia Very frequent [Orphanet] 956962; 13840590; 535190 IBIS 51 / 7739
25
 (HPO:0002197) Generalized seizures 956962 IBIS 30 / 7739
26
 (HPO:0002611) Cholestatic liver disease 28331055 IBIS 19 / 7739
27
 (HPO:0000952) Jaundice 956962; 535190 IBIS 105 / 7739
28
 (HPO:0002240) Hepatomegaly 28331055 IBIS 467 / 7739
29
 (HPO:0001743) Abnormality of the spleen 13840590 IBIS 37 / 7739
30
 (HPO:0001744) Splenomegaly 28331055 IBIS 337 / 7739
31
 (HPO:0001541) Ascites 28331055 IBIS 94 / 7739
32
 (HPO:0004298) Abnormality of the abdominal wall 535190 IBIS 20 / 7739
33
 (HPO:0002715) Abnormality of the immune system 535190 IBIS 46 / 7739
34
 (HPO:0000407) Sensorineural hearing impairment 28331055 IBIS 524 / 7739
35
 (HPO:0008619) Bilateral sensorineural hearing impairment 19043416 IBIS 23 / 7739
36
 (HPO:0010515) Aplasia/Hypoplasia of the thymus Very frequent [Orphanet] 19043417 IBIS 17 / 7739
37
 (HPO:0005359) Aplasia of the thymus 956962; 13840590; 535190 IBIS 6 / 7739
38
 (HPO:0000778) Hypoplasia of the thymus 19043417; 956962; 535190 IBIS 13 / 7739
39
 (HPO:0002716) Lymphadenopathy 28331055 IBIS 129 / 7739
40
 (HPO:0000961) Cyanosis 956962 IBIS 60 / 7739
41
 (HPO:0001019) Erythroderma 28331055 IBIS 24 / 7739
42
 (HPO:0200042) Skin ulcer Occasional [Orphanet] 956962; 535190 IBIS 138 / 7739
43
 (HPO:0001873) Thrombocytopenia 28331055 IBIS 224 / 7739
44
 (HPO:0001622) Premature birth 956962; 13840590; 28331055 IBIS 100 / 7739
45
 (HPO:0001522) Death in infancy Frequent [Orphanet] 19043417; 956962 IBIS 275 / 7739
46
 (HPO:0003811) Neonatal death 956962; 13840590; 535190 IBIS 44 / 7739
47
 (MedDRA:10061308) Neonatal infection 535190 IBIS 2 / 7739
48
 (MedDRA:10030306) Omphalitis 28331055; 535190 IBIS 2 / 7739

Associated genes:

AK2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Reticular dysgenesis is one of the rarest and most severe forms of combined immunodeficiency. It is characterized by congenital agranulocytosis, lymphopenia, and lymphoid and thymic hypoplasia with absent cellular and humoral immunity functions. De Vaal and Seynhaeve (1959) described ...
Molecular genetics OMIM Pannicke et al. (2009) noted that 80 genes within the reticular dysgenesis critical region on chromosome 1 are expected to be expressed in bone marrow. They used RT-PCR to examine the expression of these genes in bone marrow mononuclear ...