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Granulocytopenia with immunoglobulin abnormality(IMD59)

MedGen UID:
383874
Concept ID:
C1856263
Disease or Syndrome
Synonym: Granulocytopenia with Immunoglobulin Abnormality
 
Gene (location): HYOU1 (11q23.3)
 
Monarch Initiative: MONDO:0009305
OMIM®: 233600

Definition

Immunodeficiency-59 and hypoglycemia (IMD59) is an autosomal recessive primary immunologic disorder characterized by combined immunodeficiency and recurrent septic infections of the respiratory tract, skin, and mucous membranes, as well as disturbed glucose metabolism. Granulocytopenia and B-cell and dendritic cell deficiency are present (Haapaniemi et al., 2017). [from OMIM]

Clinical features

From HPO
Slender finger
MedGen UID:
387832
Concept ID:
C1857482
Finding
Fingers that are disproportionately narrow (reduced girth) for the hand/foot size or build of the individual.
Arteritis
MedGen UID:
13916
Concept ID:
C0003860
Pathologic Function
Arterial inflammation.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Prolonged neonatal jaundice
MedGen UID:
347108
Concept ID:
C1859236
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Malabsorption
MedGen UID:
811453
Concept ID:
C3714745
Finding
Impaired ability to absorb one or more nutrients from the intestine.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Acne inversa
MedGen UID:
57993
Concept ID:
C0162836
Disease or Syndrome
A chronic skin condition involving the inflammation of the apocrine sweat glands, forming pimple-like bumps known as abscesses.
Herpes simplex encephalitis
MedGen UID:
75794
Concept ID:
C0276226
Disease or Syndrome
Infection of the brain parenchyma with herpes simplex virus, resulting in inflammation of the brain parenchyma with neurologic dysfunction.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Disease or Syndrome
Infections of the skin that happen multiple times.
Decreased circulating antibody concentration
MedGen UID:
892481
Concept ID:
C4048270
Finding
An abnormally decreased level of immunoglobulin in blood.
Decreased proportion of class-switched memory B cells
MedGen UID:
892709
Concept ID:
C4072925
Finding
A reduction in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA.
Complete or near-complete absence of specific antibody response to unconjugated pneumococcus vaccine
MedGen UID:
1704477
Concept ID:
C5139463
Finding
The inability to synthesize postvaccination antibodies against a pneumococcus antigen, as measured by antibody titer determination following vaccination.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Narrow nose
MedGen UID:
98086
Concept ID:
C0426422
Finding
Interalar distance more than 2 SD below the mean for age, or alternatively, an apparently decreased width of the nasal base and alae.
Narrow face
MedGen UID:
373334
Concept ID:
C1837463
Finding
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
Oval face
MedGen UID:
336480
Concept ID:
C1849025
Finding
A face with a rounded and slightly elongated outline.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Recurrent aphthous stomatitis
MedGen UID:
445425
Concept ID:
C2937365
Disease or Syndrome
Recurrent episodes of ulceration of the oral mucosa, typically presenting as painful, sharply circumscribed fibrin-covered mucosal defects with a hyperemic border.
High anterior hairline
MedGen UID:
477667
Concept ID:
C3276036
Finding
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella.

Professional guidelines

PubMed

Afzal W, Owlia MB, Hasni S, Newman KA
South Med J 2017 Apr;110(4):300-307. doi: 10.14423/SMJ.0000000000000637. PMID: 28376530
Pontikoglou C, Kalpadakis C, Papadaki HA
Expert Rev Hematol 2011 Jun;4(3):317-28. doi: 10.1586/ehm.11.26. PMID: 21668396
Higdon ML, Higdon JA
Am Fam Physician 2006 Dec 1;74(11):1873-80. PMID: 17168344

Recent clinical studies

Etiology

Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P
Lancet Haematol 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30 doi: 10.1016/S2352-3026(20)30099-5. PMID: 32359506
Kumari R, Timshina DK, Thappa DM
Indian J Dermatol Venereol Leprol 2011 Jan-Feb;77(1):7-15. doi: 10.4103/0378-6323.74964. PMID: 21220873
Akhtari M, Curtis B, Waller EK
Autoimmun Rev 2009 Sep;9(1):62-6. Epub 2009 Mar 14 doi: 10.1016/j.autrev.2009.03.006. PMID: 19293004
Higdon ML, Higdon JA
Am Fam Physician 2006 Dec 1;74(11):1873-80. PMID: 17168344
Capsoni F, Sarzi-Puttini P, Zanella A
Arthritis Res Ther 2005;7(5):208-14. Epub 2005 Aug 31 doi: 10.1186/ar1803. PMID: 16207350Free PMC Article

Diagnosis

Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P
Lancet Haematol 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30 doi: 10.1016/S2352-3026(20)30099-5. PMID: 32359506
Kumari R, Timshina DK, Thappa DM
Indian J Dermatol Venereol Leprol 2011 Jan-Feb;77(1):7-15. doi: 10.4103/0378-6323.74964. PMID: 21220873
Akhtari M, Curtis B, Waller EK
Autoimmun Rev 2009 Sep;9(1):62-6. Epub 2009 Mar 14 doi: 10.1016/j.autrev.2009.03.006. PMID: 19293004
Young GA, Vincent PC
Clin Haematol 1980 Oct;9(3):483-504. PMID: 7004683
Spivak JL
Johns Hopkins Med J 1977 Sep;141(3):156-62. PMID: 330914

Therapy

Hamadani M, Radford J, Carlo-Stella C, Caimi PF, Reid E, O'Connor OA, Feingold JM, Ardeshna KM, Townsend W, Solh M, Heffner LT, Ungar D, Wang L, Boni J, Havenith K, Qin Y, Kahl BS
Blood 2021 May 13;137(19):2634-2645. doi: 10.1182/blood.2020007512. PMID: 33211842Free PMC Article
Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P
Lancet Haematol 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30 doi: 10.1016/S2352-3026(20)30099-5. PMID: 32359506
Kumari R, Timshina DK, Thappa DM
Indian J Dermatol Venereol Leprol 2011 Jan-Feb;77(1):7-15. doi: 10.4103/0378-6323.74964. PMID: 21220873
Higdon ML, Higdon JA
Am Fam Physician 2006 Dec 1;74(11):1873-80. PMID: 17168344
Young GA, Vincent PC
Clin Haematol 1980 Oct;9(3):483-504. PMID: 7004683

Prognosis

Karlowicz JR, Klakegg M, Aarseth JH, Bø L, Myhr KM, Torgauten HM, Torkildsen Ø, Wergeland S
Mult Scler Relat Disord 2023 Mar;71:104556. Epub 2023 Feb 11 doi: 10.1016/j.msard.2023.104556. PMID: 36842313
Hamadani M, Radford J, Carlo-Stella C, Caimi PF, Reid E, O'Connor OA, Feingold JM, Ardeshna KM, Townsend W, Solh M, Heffner LT, Ungar D, Wang L, Boni J, Havenith K, Qin Y, Kahl BS
Blood 2021 May 13;137(19):2634-2645. doi: 10.1182/blood.2020007512. PMID: 33211842Free PMC Article
Ibrahim U, Keyzner A
Hematol Oncol Stem Cell Ther 2021 Jun;14(2):104-109. Epub 2020 Aug 26 doi: 10.1016/j.hemonc.2020.07.009. PMID: 32882204
Kumari R, Timshina DK, Thappa DM
Indian J Dermatol Venereol Leprol 2011 Jan-Feb;77(1):7-15. doi: 10.4103/0378-6323.74964. PMID: 21220873
Capsoni F, Sarzi-Puttini P, Zanella A
Arthritis Res Ther 2005;7(5):208-14. Epub 2005 Aug 31 doi: 10.1186/ar1803. PMID: 16207350Free PMC Article

Clinical prediction guides

Karlowicz JR, Klakegg M, Aarseth JH, Bø L, Myhr KM, Torgauten HM, Torkildsen Ø, Wergeland S
Mult Scler Relat Disord 2023 Mar;71:104556. Epub 2023 Feb 11 doi: 10.1016/j.msard.2023.104556. PMID: 36842313
Pehlivan UA, Gürkan E, Açar İH, Bıçakcı YK
J Oncol Pharm Pract 2023 Jan;29(1):246-251. Epub 2022 May 20 doi: 10.1177/10781552221102591. PMID: 35593112
Ganju A, Stock JC, Jordan K
J Pharm Pract 2023 Feb;36(1):168-172. Epub 2021 Jun 25 doi: 10.1177/08971900211021235. PMID: 34169768
Fleischmann R, Genovese MC, Maslova K, Leher H, Praestgaard A, Burmester GR
Rheumatology (Oxford) 2021 Nov 3;60(11):4991-5001. doi: 10.1093/rheumatology/keab355. PMID: 33871596
Guiddir T, Frémond ML, Triki TB, Candon S, Croisille L, Leblanc T, de Pontual L
Pediatrics 2014 Oct;134(4):e1189-93. doi: 10.1542/peds.2014-0054. PMID: 25266439

Recent systematic reviews

Lee A, Arasaratnam M, Chan DLH, Khasraw M, Howell VM, Wheeler H
Cochrane Database Syst Rev 2020 May 12;5(5):CD013238. doi: 10.1002/14651858.CD013238.pub2. PMID: 32395825Free PMC Article

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