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Neonatal hemochromatosis

MedGen UID:
82768
Concept ID:
C0268059
Disease or Syndrome
Synonyms: ALLOIMMUNE HEPATITIS, CONGENITAL; NEONATAL HEPATITIS
SNOMED CT: Neonatal hemochromatosis (6160004); Idiopathic neonatal hemochromatosis (6160004)
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).
 
Monarch Initiative: MONDO:0009275
OMIM®: 231100
Orphanet: ORPHA446

Definition

Neonatal hemochromatosis (NH) is characterized by hepatic failure in the newborn period and heavy iron staining in the liver. In addition, there is marked siderosis of extrahepatic tissues, including the heart and pancreas (Driscoll et al., 1988). Whitington (2007) postulated that some cases of neonatal hemochromatosis result from maternal alloimmunity directed at the fetal liver, and therefore do not represent an inherited mendelian disorder. Other causes may result from metabolic disease or perinatal infection. In particular, he commented that the disorder is not related to the family of inherited liver diseases that fall under the classification of hereditary hemochromatosis (see, e.g., 235200). Whitington (2007) proposed the term 'congenital alloimmune hepatitis.' In the past, the disorder has loosely been labeled 'neonatal hepatitis' and 'giant cell hepatitis,' which are pathologic findings in the liver representing a common response to a variety of insults, including cholestatic disorders and infection, among others (Fawaz et al., 1975; Knisely et al., 1987; Kelly et al., 2001). [from OMIM]

Clinical features

From HPO
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Cholestasis
MedGen UID:
925
Concept ID:
C0008370
Disease or Syndrome
Impairment of bile flow due to obstruction in bile ducts.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Hepatocellular necrosis
MedGen UID:
343247
Concept ID:
C1855038
Disease or Syndrome
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.
Abnormal bleeding
MedGen UID:
264316
Concept ID:
C1458140
Pathologic Function
An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Increased serum iron
MedGen UID:
57739
Concept ID:
C0151900
Finding
Increased circulating ferritin concentration
MedGen UID:
69130
Concept ID:
C0241013
Finding
Increased concentration of ferritin in the blood circulation.
Abnormality of iron homeostasis
MedGen UID:
869163
Concept ID:
C4023583
Finding
An abnormality of the homeostasis (concentration) of iron cation.
Oligohydramnios
MedGen UID:
86974
Concept ID:
C0079924
Pathologic Function
Diminished amniotic fluid volume in pregnancy.
Non-immune hydrops fetalis
MedGen UID:
105327
Concept ID:
C0455988
Disease or Syndrome
Hydrops fetalis is a descriptive term for generalized edema of the fetus, with fluid accumulation in extravascular components and body cavities. It is not a diagnosis in itself, but a symptom and end-stage result of a wide variety of disorders. In the case of immune hydrops fetalis, a frequent cause is maternofetal incompatibility as in that related to a number of genetic anemias and metabolic disorders expressed in the fetus; in other instances, it remains idiopathic and likely multifactorial (summary by Bellini et al., 2009). Nonimmune hydrops fetalis accounts for 76 to 87% of all described cases of hydrops fetalis (Bellini et al., 2009). Genetic Heterogeneity of Hydrops Fetalis In southeast Asia, alpha-thalassemia (604131) is the most common cause of hydrops fetalis, accounting for 60 to 90% of cases. Almost all of these cases result from homozygous deletion of the HBA1 (141800) and HBA2 (141850) genes. A few cases have been reported that had 1 apparently normal alpha-globin gene, termed the hemoglobin H (613978) hydrops fetalis syndrome (summary by Chui and Waye, 1998). Other genetic disorders predisposing to NIHF include other congenital anemias, such as erythropoietic porphyria (e.g., 606938.0013), and many metabolic disorders, such as one form of Gaucher disease (e.g., 606463.0009), infantile sialic acid storage disease (269920), mucopolysaccharidosis type VII (253220), glycogen storage disease IV (232500), congenital disorder of glycosylation type Ia (212065), and disorders of lymphatic malformation (see, e.g., LMPHM1, 153100).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNeonatal hemochromatosis
Follow this link to review classifications for Neonatal hemochromatosis in Orphanet.

Professional guidelines

PubMed

Lopriore E, Mearin ML, Oepkes D, Devlieger R, Whitington PF
Prenat Diagn 2013 Dec;33(13):1221-5. Epub 2013 Oct 4 doi: 10.1002/pd.4232. PMID: 24030714
Shanmugam NP, Bansal S, Greenough A, Verma A, Dhawan A
Eur J Pediatr 2011 May;170(5):573-81. Epub 2010 Oct 2 doi: 10.1007/s00431-010-1309-1. PMID: 20886352
Ekong U
Pediatr Transplant 2007 Jun;11(4):347-8. doi: 10.1111/j.1399-3046.2007.00708.x. PMID: 17493212

Recent clinical studies

Etiology

Maisonneuve E, Ben M'Barek I, Leblanc T, Da Costa L, Friszer S, Pernot F, Thomas P, Castaigne V, Toly N'Dour C, Mailloux A, Cortey A, Jouannic JM
Fetal Diagn Ther 2020;47(2):156-164. Epub 2019 Sep 10 doi: 10.1159/000501554. PMID: 31505487
Kasko O, Klose E, Rama G, Newberry D, Jnah A
Neonatal Netw 2018 Sep;37(5):271-280. doi: 10.1891/0730-0832.37.5.271. PMID: 30567809
Bitar R, Thwaites R, Davison S, Rajwal S, McClean P
J Pediatr Gastroenterol Nutr 2017 Jan;64(1):70-75. doi: 10.1097/MPG.0000000000001202. PMID: 27007398
Lee CK, Jonas MM
Curr Opin Gastroenterol 2007 May;23(3):306-9. doi: 10.1097/MOG.0b013e32805b716d. PMID: 17414847
Knisely AS, Mieli-Vergani G, Whitington PF
Gastroenterol Clin North Am 2003 Sep;32(3):877-89, vi-vii. doi: 10.1016/s0889-8553(03)00050-5. PMID: 14562579

Diagnosis

Chavhan GB, Kamath BM, Siddiqui I, Tomlinson C
Pediatr Radiol 2022 Feb;52(2):334-339. Epub 2021 Mar 12 doi: 10.1007/s00247-021-05008-9. PMID: 33710405
Kasko O, Klose E, Rama G, Newberry D, Jnah A
Neonatal Netw 2018 Sep;37(5):271-280. doi: 10.1891/0730-0832.37.5.271. PMID: 30567809
Whitington PF
Semin Liver Dis 2012 Nov;32(4):325-32. Epub 2013 Feb 8 doi: 10.1055/s-0032-1329901. PMID: 23397533
Knisely AS, Mieli-Vergani G, Whitington PF
Gastroenterol Clin North Am 2003 Sep;32(3):877-89, vi-vii. doi: 10.1016/s0889-8553(03)00050-5. PMID: 14562579
Cox TM, Halsall DJ
Blood Cells Mol Dis 2002 Nov-Dec;29(3):411-7. doi: 10.1006/bcmd.2002.0580. PMID: 12547231

Therapy

Tsuge M, Kodera A, Sumitomo H, Araki T, Yoshida R, Yasui K, Sato H, Washio Y, Washio K, Shigehara K, Yashiro M, Yagi T, Tsukahara H
BMC Pediatr 2022 Oct 29;22(1):622. doi: 10.1186/s12887-022-03706-3. PMID: 36309641Free PMC Article
Maisonneuve E, Ben M'Barek I, Leblanc T, Da Costa L, Friszer S, Pernot F, Thomas P, Castaigne V, Toly N'Dour C, Mailloux A, Cortey A, Jouannic JM
Fetal Diagn Ther 2020;47(2):156-164. Epub 2019 Sep 10 doi: 10.1159/000501554. PMID: 31505487
Kasko O, Klose E, Rama G, Newberry D, Jnah A
Neonatal Netw 2018 Sep;37(5):271-280. doi: 10.1891/0730-0832.37.5.271. PMID: 30567809
Korkmaz L, Baştuğ O, Daar G, Doğanay S, Deniz K, Kurtoğlu S
J Neonatal Perinatal Med 2015;8(4):413-6. doi: 10.3233/NPM-1577113. PMID: 26836824
Sigurdsson L, Reyes J, Kocoshis SA, Hansen TW, Rosh J, Knisely AS
J Pediatr Gastroenterol Nutr 1998 Jan;26(1):85-9. doi: 10.1097/00005176-199801000-00015. PMID: 9443126

Prognosis

Kasko O, Klose E, Rama G, Newberry D, Jnah A
Neonatal Netw 2018 Sep;37(5):271-280. doi: 10.1891/0730-0832.37.5.271. PMID: 30567809
Lopriore E, Mearin ML, Oepkes D, Devlieger R, Whitington PF
Prenat Diagn 2013 Dec;33(13):1221-5. Epub 2013 Oct 4 doi: 10.1002/pd.4232. PMID: 24030714
Lee CK, Jonas MM
Curr Opin Gastroenterol 2007 May;23(3):306-9. doi: 10.1097/MOG.0b013e32805b716d. PMID: 17414847
Knisely AS, Mieli-Vergani G, Whitington PF
Gastroenterol Clin North Am 2003 Sep;32(3):877-89, vi-vii. doi: 10.1016/s0889-8553(03)00050-5. PMID: 14562579
Blisard KS, Bartow SA
Hum Pathol 1986 Apr;17(4):376-83. doi: 10.1016/s0046-8177(86)80461-0. PMID: 3957336

Clinical prediction guides

Zozaya Nieto C, Fernández Caamaño B, Muñoz Bartolo G, Menéndez Suso JJ, Frauca Remacha E, Valverde Núñez E
J Pediatr Gastroenterol Nutr 2017 May;64(5):754-759. doi: 10.1097/MPG.0000000000001501. PMID: 28437325
Lee CK, Jonas MM
Curr Opin Gastroenterol 2007 May;23(3):306-9. doi: 10.1097/MOG.0b013e32805b716d. PMID: 17414847
Knisely AS, Mieli-Vergani G, Whitington PF
Gastroenterol Clin North Am 2003 Sep;32(3):877-89, vi-vii. doi: 10.1016/s0889-8553(03)00050-5. PMID: 14562579
Cox TM, Halsall DJ
Blood Cells Mol Dis 2002 Nov-Dec;29(3):411-7. doi: 10.1006/bcmd.2002.0580. PMID: 12547231
Bottomley SS
Semin Hematol 1998 Jan;35(1):77-86. PMID: 9460811

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