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Pancreatic insufficiency-anemia-hyperostosis syndrome

MedGen UID:
436369
Concept ID:
C2675184
Disease or Syndrome
Synonym: Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis
SNOMED CT: Pancreatic insufficiency, dyserythropoietic anemia, calvarial hyperostosis syndrome (722207000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): COX4I2 (20q11.21)
 
Monarch Initiative: MONDO:0012992
OMIM®: 612714
Orphanet: ORPHA199337

Definition

This syndrome is characterized by exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis. It has been described in four children, three boys and one girl, from two consanguineous families. The disease is due to a mutation in the COX4I2 gene, encoding a mitochondrial cytochrome C oxidase sub-unit. Transmission is autosomal recessive. [from SNOMEDCT_US]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Steatorrhea
MedGen UID:
20948
Concept ID:
C0038238
Finding
Greater than normal amounts of fat in the feces. This is a result of malabsorption of lipids in the small intestine and results in frothy foul-smelling fecal matter that floats.
Malnutrition
MedGen UID:
56429
Concept ID:
C0162429
Disease or Syndrome
A deficiency in the intake of energy and nutrients.
Exocrine pancreatic insufficiency
MedGen UID:
75647
Concept ID:
C0267963
Disease or Syndrome
Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Anemia of inadequate production
MedGen UID:
95937
Concept ID:
C0392708
Pathologic Function
A kind of anemia characterized by inadequate production of erythrocytes.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Calvarial hyperostosis
MedGen UID:
350147
Concept ID:
C1863351
Finding
Excessive growth of the calvaria.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Allergic rhinitis
MedGen UID:
382012
Concept ID:
C2607914
Disease or Syndrome
It is characterized by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhea.
Skin rash
MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
A red eruption of the skin.
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPancreatic insufficiency-anemia-hyperostosis syndrome
Follow this link to review classifications for Pancreatic insufficiency-anemia-hyperostosis syndrome in Orphanet.

Professional guidelines

PubMed

Shimizu K, Ito T, Irisawa A, Ohtsuka T, Ohara H, Kanno A, Kida M, Sakagami J, Sata N, Takeyama Y, Tahara J, Hirota M, Fujimori N, Masamune A, Mochida S, Enomoto N, Shimosegawa T, Koike K
J Gastroenterol 2022 Oct;57(10):709-724. Epub 2022 Aug 22 doi: 10.1007/s00535-022-01911-6. PMID: 35994093Free PMC Article
Baron TH, DiMaio CJ, Wang AY, Morgan KA
Gastroenterology 2020 Jan;158(1):67-75.e1. Epub 2019 Aug 31 doi: 10.1053/j.gastro.2019.07.064. PMID: 31479658
ASGE Standards of Practice Committee, Buxbaum JL, Abbas Fehmi SM, Sultan S, Fishman DS, Qumseya BJ, Cortessis VK, Schilperoort H, Kysh L, Matsuoka L, Yachimski P, Agrawal D, Gurudu SR, Jamil LH, Jue TL, Khashab MA, Law JK, Lee JK, Naveed M, Sawhney MS, Thosani N, Yang J, Wani SB
Gastrointest Endosc 2019 Jun;89(6):1075-1105.e15. Epub 2019 Apr 9 doi: 10.1016/j.gie.2018.10.001. PMID: 30979521Free PMC Article

Recent clinical studies

Etiology

Shimizu K, Ito T, Irisawa A, Ohtsuka T, Ohara H, Kanno A, Kida M, Sakagami J, Sata N, Takeyama Y, Tahara J, Hirota M, Fujimori N, Masamune A, Mochida S, Enomoto N, Shimosegawa T, Koike K
J Gastroenterol 2022 Oct;57(10):709-724. Epub 2022 Aug 22 doi: 10.1007/s00535-022-01911-6. PMID: 35994093Free PMC Article
Beyer G, Habtezion A, Werner J, Lerch MM, Mayerle J
Lancet 2020 Aug 15;396(10249):499-512. doi: 10.1016/S0140-6736(20)31318-0. PMID: 32798493
Gardner TB, Adler DG, Forsmark CE, Sauer BG, Taylor JR, Whitcomb DC
Am J Gastroenterol 2020 Mar;115(3):322-339. doi: 10.14309/ajg.0000000000000535. PMID: 32022720
Baron TH, DiMaio CJ, Wang AY, Morgan KA
Gastroenterology 2020 Jan;158(1):67-75.e1. Epub 2019 Aug 31 doi: 10.1053/j.gastro.2019.07.064. PMID: 31479658
Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology
Am J Gastroenterol 2013 Sep;108(9):1400-15; 1416. Epub 2013 Jul 30 doi: 10.1038/ajg.2013.218. PMID: 23896955

Diagnosis

Shimizu K, Ito T, Irisawa A, Ohtsuka T, Ohara H, Kanno A, Kida M, Sakagami J, Sata N, Takeyama Y, Tahara J, Hirota M, Fujimori N, Masamune A, Mochida S, Enomoto N, Shimosegawa T, Koike K
J Gastroenterol 2022 Oct;57(10):709-724. Epub 2022 Aug 22 doi: 10.1007/s00535-022-01911-6. PMID: 35994093Free PMC Article
Beyer G, Habtezion A, Werner J, Lerch MM, Mayerle J
Lancet 2020 Aug 15;396(10249):499-512. doi: 10.1016/S0140-6736(20)31318-0. PMID: 32798493
Gardner TB, Adler DG, Forsmark CE, Sauer BG, Taylor JR, Whitcomb DC
Am J Gastroenterol 2020 Mar;115(3):322-339. doi: 10.14309/ajg.0000000000000535. PMID: 32022720
Baron TH, DiMaio CJ, Wang AY, Morgan KA
Gastroenterology 2020 Jan;158(1):67-75.e1. Epub 2019 Aug 31 doi: 10.1053/j.gastro.2019.07.064. PMID: 31479658
Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology
Am J Gastroenterol 2013 Sep;108(9):1400-15; 1416. Epub 2013 Jul 30 doi: 10.1038/ajg.2013.218. PMID: 23896955

Therapy

Shimizu K, Ito T, Irisawa A, Ohtsuka T, Ohara H, Kanno A, Kida M, Sakagami J, Sata N, Takeyama Y, Tahara J, Hirota M, Fujimori N, Masamune A, Mochida S, Enomoto N, Shimosegawa T, Koike K
J Gastroenterol 2022 Oct;57(10):709-724. Epub 2022 Aug 22 doi: 10.1007/s00535-022-01911-6. PMID: 35994093Free PMC Article
Hernandez P, Passi N, Modarressi T, Kulkarni V, Soni M, Burke F, Bajaj A, Soffer D
Curr Atheroscler Rep 2021 Sep 13;23(11):72. doi: 10.1007/s11883-021-00962-z. PMID: 34515873Free PMC Article
Baron TH, DiMaio CJ, Wang AY, Morgan KA
Gastroenterology 2020 Jan;158(1):67-75.e1. Epub 2019 Aug 31 doi: 10.1053/j.gastro.2019.07.064. PMID: 31479658
Parhofer KG, Laufs U
Dtsch Arztebl Int 2019 Dec 6;116(49):825-832. doi: 10.3238/arztebl.2019.0825. PMID: 31888796Free PMC Article
Habtezion A, Gukovskaya AS, Pandol SJ
Gastroenterology 2019 May;156(7):1941-1950. Epub 2019 Jan 18 doi: 10.1053/j.gastro.2018.11.082. PMID: 30660726Free PMC Article

Prognosis

Shimizu K, Ito T, Irisawa A, Ohtsuka T, Ohara H, Kanno A, Kida M, Sakagami J, Sata N, Takeyama Y, Tahara J, Hirota M, Fujimori N, Masamune A, Mochida S, Enomoto N, Shimosegawa T, Koike K
J Gastroenterol 2022 Oct;57(10):709-724. Epub 2022 Aug 22 doi: 10.1007/s00535-022-01911-6. PMID: 35994093Free PMC Article
Gardner TB, Adler DG, Forsmark CE, Sauer BG, Taylor JR, Whitcomb DC
Am J Gastroenterol 2020 Mar;115(3):322-339. doi: 10.14309/ajg.0000000000000535. PMID: 32022720
Gutta A, Fogel E, Sherman S
Expert Rev Gastroenterol Hepatol 2019 Nov;13(11):1089-1105. Epub 2019 Nov 8 doi: 10.1080/17474124.2019.1685871. PMID: 31663403Free PMC Article
Nassar TI, Qunibi WY
Clin J Am Soc Nephrol 2019 Jul 5;14(7):1106-1115. Epub 2019 May 22 doi: 10.2215/CJN.13191118. PMID: 31118209Free PMC Article
Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology
Am J Gastroenterol 2013 Sep;108(9):1400-15; 1416. Epub 2013 Jul 30 doi: 10.1038/ajg.2013.218. PMID: 23896955

Clinical prediction guides

Ammer-Herrmenau C, Antweiler KL, Asendorf T, Beyer G, Buchholz SM, Cameron S, Capurso G, Damm M, Dang L, Frost F, Gomes A, Hamm J, Henker R, Hoffmeister A, Meinhardt C, Nawacki L, Nunes V, Panyko A, Pardo C, Phillip V, Pukitis A, Rasch S, Riekstina D, Rinja E, Ruiz-Rebollo ML, Sirtl S, Weingarten M, Sandru V, Woitalla J, Ellenrieder V, Neesse A
Gut 2024 Feb 23;73(3):485-495. doi: 10.1136/gutjnl-2023-330987. PMID: 38129103Free PMC Article
Liu F, Yao J, Liu C, Shou S
BMC Surg 2023 Sep 1;23(1):267. doi: 10.1186/s12893-023-02151-y. PMID: 37658375Free PMC Article
Oppenlander KE, Chadwick C, Carman K
Am Fam Physician 2022 Jul;106(1):44-50. PMID: 35839366
Beyer G, Habtezion A, Werner J, Lerch MM, Mayerle J
Lancet 2020 Aug 15;396(10249):499-512. doi: 10.1016/S0140-6736(20)31318-0. PMID: 32798493
Gutta A, Fogel E, Sherman S
Expert Rev Gastroenterol Hepatol 2019 Nov;13(11):1089-1105. Epub 2019 Nov 8 doi: 10.1080/17474124.2019.1685871. PMID: 31663403Free PMC Article

Recent systematic reviews

Wilson RB, Lathigara D, Kaushal D
Int J Mol Sci 2023 Mar 24;24(7) doi: 10.3390/ijms24076192. PMID: 37047163Free PMC Article
Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, Park S, Hegyi P, Nyirády P, Ács N, Várbíró S, Horváth EM
Reprod Biol Endocrinol 2023 Jan 26;21(1):10. doi: 10.1186/s12958-023-01055-z. PMID: 36703143Free PMC Article
Larsson SC, Burgess S
EBioMedicine 2022 Aug;82:104154. Epub 2022 Jul 8 doi: 10.1016/j.ebiom.2022.104154. PMID: 35816897Free PMC Article
Lee YC, Lee YL, Li CY
Medicina (Kaunas) 2021 Aug 30;57(9) doi: 10.3390/medicina57090905. PMID: 34577828Free PMC Article
Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D
Diabetes Care 2012 Nov;35(11):2402-11. doi: 10.2337/dc12-0336. PMID: 23093685Free PMC Article

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