Children, newborn screening, Juvenile hemochromatosis (JH), 
Neonatal Hemochromatosis [NH], pregnancy, young adults, etc.
Click on the title to read how children may be affected by too much iron.

Click below to see a table of lab values for children, ages 1 day to 19 yrs. old
[Special thanks to Jim Hines for converting these to tables for me!]

• Hemoglobin, Hematocrit, RBC, MCV, MCH, MCHC

• Ferritin, Iron, TIBC, Transferrin Saturation,
  Transferrin, Folic Acid, Vit. B12

The above tables were taken from:  Nathan & Oskis Hematology of Infancy & Childhood,
5th Edition, Vol. 2, copyrighted 74, 81, 87, 93, 98 
edited by David G. Nathan & Stuart H. Orkin, of Harvard Medical School

• A population based study of the clinical expression of the clinical expression of the Hemochromatosis gene NEJM Sept 1999  Our findings have implications for population screening for hereditary hemochromatosis. 
   

• Association of sudden infant death syndrome with grossly deranged iron metabolism and nitric oxide overload  Med Hypotheses 2000 Jan;
  
• Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis   Parkkila S, Waheed A, Britton RS, Bacon BR, Zhou XY, Tomatsu S, Fleming RE, Sly WS The Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, MO 63104, USA Proc Natl Acad Sci U S A 1997 Nov 25.  These studies place the normal HFE protein at the site of contact with the maternal circulation where its association with transferrin receptor raises the possibility that the HFE protein plays some role in determining maternal/fetal iron homeostasis.
  
• Baby Formula -- Chemical Composition  Ask a Scientist 
  
• Body iron stores in relation to growth and pubertal maturation in healthy boys. 
  Br J Haematol 1997 Jan;96(1):12-8  During male puberty, erythropoiesis is exceptionally active.
  
• Breastfeeding and iron status  
  InFact Canada newsletter Fall 97  Are artificially fed infants at risk for receiving too much iron from birth through supplementation and/or fortification of baby milks and complementary foods?
  
• Classification and diagnosis of iron overload  
  Haematologica 1998 May The recent description of new conditions associated with iron overload and the identification of the genetic defect of hereditary hemochromatosis prompted us to review this subject and to redefine the diagnostic criteria of iron overload disorders.
  
• Clinical and molecular aspects of juvenile hemochromatosis in Saguenay-Lac-Saint-Jean (Quebec, canada)  Blood Cells Mol Dis 2000 Feb   Although the mean age at onset of the first symptoms was 21. 5 years, their mean age at diagnosis was 23.8 years; the diagnosis was particularly delayed among women. Seventy-seven percent of the patients had hypogonadotrophic hypogonadism and 69% heart failure and/or cardiac arrhythmias.
  
• Diagnosis of liver cirrhosis in children based on colour Doppler ultrasonography with histopathological correlation.  Pediatr Radiol 1998 Nov  Portal vein velocity, arterio-portal vein ratio and hepatic artery visualisation together were reliable in diagnosis of cirrhosis in the paediatric age group
  
• Dietary Iron Supplements - Use or not to use?  Nutrition Today James R. Connor John L. Beard 05-06-1997 There is little reason to support a general need for iron supplementation in the diet at any age. Perhaps this article and review of supplementation pros and cons should conclude with a new interpretation of an old saying: "It is better to wear out than to rust out;" don't expose your system to more iron than it needs.
  
• Does a nursing mom need to take iron?   iVillage/ParentsPlace.com  Iron deficiency is uncommon in breastfed babies during the first six months of life.
  
• Effects of HFE C282Y and H63D Polymorphisms and Polygenic Background on Iron Stores in a Large Community Sample of Twins Am. J. Hum. Genet., 66:1246-1258, 2000 These studies and the present study show that HFE polymorphisms affect iron stores even among heterozygotes but that ferritin is less affected than is transferrin saturation.
  
• Genetic hemochromatosis, a Celtic disease: is it now time for population screening?  Genet Test 2001 Summer;The high C282Y allele frequency in the Irish population together with its close linkage to HH indicate that C282Y genotyping is the preferred screening strategy for this disease in Ireland.
  
• Hemochromatosis: A Common, Rarely Diagnosed Disease 
  By Vincent J. Felitti, MD, FACP  Commentary by David Baer, MD, FACP.  Hemochromatosis is the most common, life-threatening genetic disorder in North America, yet most physicians have never personally diagnosed a case: all see an unrecognized case in their offices every two weeks.

• Hereditary Haemochromatosis and Iron Metabolism, Carlson J, Olsson S, eJIFCC vol 13 no 2, THE JOURNAL OF THE INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY.  An early laboratory finding seen in HH is an abnormal saturation of transferrin (TS)to a level >45% (33). This elevation is absent in rapidly growing adolescent males and in menstruating and reproducing females.

• Hereditary hemochromatosis in children, adolescents, and young adults.  Am J Pediatr Hematol Oncol. 1988 Spring  Young individuals who should be screened for iron overload include patients with cardiac myopathies, hypogonadism, amenorrhea, loss of libido, diabetes mellitus, other endocrine disorders, cirrhosis of the liver, and arthritis, as well as the siblings, parents, and children of patients with hereditary hemochromatosis or iron loading of unknown cause.
  
• Heterozygosity for the C282Y mutation in the hemochromatosis gene is associated with increased serum iron, transferrin saturation, and hemoglobin in young women:
  a protective role against iron deficiency? Clinical Chemistry. 1998;44:2429-2432

• High incidence of blood disease in Irish babies  
  Irish Medical Times April 14, 2000 Routine genetic testing of newborn babies may be warranted because of the high incidence of a serious blood disease in the Irish population. Dr John Crowe, gastroenterologist at the Centre for Liver Disease, Mater Hospital said that one in 86 Irish babies are genetically predisposed to haemachromatosis, which is the highest incidence in the world.
  
• Hypophyseal gonadotropin insufficiency in a young woman with idiopathic hemochromatosis
  Isr J Med Sci 1981   May A 24-year-old women suffering from primary sterility was diagnosed in 1971 as having idiopathic hemochromatosis (IH).

• Hypothyroidism and hypoparathyroidism in an 11 year old boy with hemochromatosis secondary to aplastic anemia.  Acta Paediatr Jpn. 1995 Aug  This is the first reported case, to our knowledge, of hypoparathyroidism and hypothyroidism due to secondary hemochromatosis with onset during childhood. The patient was a boy with refractory aplastic anemia in whom primary hypothyroidism and hypoparathyroidism became apparent at the age of 10 and 11 years old, respectively.
  

• Idiopathic hemochromatosis presenting as amenorrhea and arthritis 
  Am J Med 1987 May A young woman with idiopathic hemochromatosis is described.
  

• Infant diet and salmonellosis Am J Public Health 1991 Aug   Interviews of case parents suggested that the use of high-iron infant formula was associated with this problem. Breast-feeding apparently protects against the development of physician-diagnosed clinical salmonellosis, while the feeding of high-iron infant formula has the opposite effect.

• Inherited iron overload.  
  Acta Paediatr Scand Suppl. 1989 Several inherited forms of iron overload have been described. It is now accepted that HC, usually regarded as a disease of adult life, is an inherited disorder, hence all first degree relatives must be presumed to be at increased risk of developing iron overload and the diagnosis is now frequently made in young relatives. The combination of serum iron, transferrin saturation and serum ferritin determination will detect iron overload in an early, precirrhotic stage
  
• Interpretation of iron studies in adolescent haemochromatosis Clin Lab Haematol 1999 Apr;21(2):129-31 This case highlights that a low serum ferritin does not exclude the diagnosis of HH and that the availability of genetic testing can now enable probands and affected family members to be identified.
  
• IRON DEPOSITION IN THE JOINTS OF CHILDREN WITH JUVENILE RHEUMATOID ARTHRITIS
  We adapted a machine called a gamma counter to measure the iron in eight patients' joints after giving them an iron isotope by vein.

• IRON FREE Multivitamins & minerals for adults & children.  www.health-pages.com  "Do You Know What's In Your Children's Chewable Multi-Vitamin? We're betting you don't. If you did, you would probably throw them away. Go get your child's current multi. If any of the following are listed on the ingredients panel, you'll want to switch to ours....."  Note: One of the ingredients listed is IRON!
   
• Iron is Hot:  An Update on the Pathophysiology of Hemochromatosis:  Blood Journal Sept. 15, 1998  Genetic iron overload disorders are prevalent yet poorly understood. [A pdf file.]
  
• Iron Loading and Disease Surveillance
  Eugene D. Weinberg   Indiana University, Bloomington, Indiana   Emerging Infectious Diseases Journal, National Center for Infectious Diseases, Centers for Disease Control and Prevention. Excessive iron in specific tissues and cells (iron loading) promotes development of infection, neoplasia, cardiomyopathy, arthropathy, and various endocrine and possibly neurodegenerative disorders.
  
• Iron overload, oxidative stress, and axonal dystrophy in brain disorders  
  Pediatr Neurol 2001 Aug
  
• Iron Poisoning  California Poison Control System Iron is important for good nutrition because it is used in blood and muscle tissue. However, it is also very poisonous if too much is taken.
  
• Liver failure with marked hyperferritinemia: 'ironing out' the diagnosis. 
  Can J Gastroenterol 2001 Aug;15(8):537-40
  
• Multiple endocrine abnormalities in a child with Blackfan-Diamond anemia and hemochromatosis.
  Significant improvement of growth velocity and predicted adult height following growth hormone treatment despite liver damage. J Pediatr Endocrinol Metab 2000 Mar;13(3):325-8

• Multiple hormone deficiencies in children with hemochromatosis  
  Journal of Clinical Endocrinology & Metabolism, Vol 76, 357-361, Copyright © 1993 by Endocrine Society.  We conclude that all patients with hemochromatosis need periodic careful endocrine evaluations because the incidence of endocrine dysfunction is substantial and they may benefit from hormonal therapy.
  
• Mutation screening for prenatal and presymptomatic diagnosis: cystic fibrosis and haemochromatosis Abstract. Eur J Pediatr 2000 Dec; Mutation analysis is widely recommended for presymptomatic diagnosis of cystic fibrosis and hereditary haemochromatosis because of the presumed benefit.  Click here for full text pdf file.
  
• Pediatric Liver Transplantation University of Virginia Health System
  
• Pediatric Iron Poisoning
  From Medscape Pharmacists Medscape, 2000  While it is clear that iron can cause serious morbidity and mortality, many families and even some clinicians are unaware of the dangers of iron.
  
• Primary hemochromatosis in childhood.
  Pediatrics 1987 Oct;80(4):549-54 Escobar GJ, Heyman MB, Smith WB, Thaler MM Department of Pediatrics, University of California, San Francisco A plan for evaluating and treating affected patients is proposed. Physicians caring for children must learn to recognize this potentially treatable disorder.
  
• Risk of disease in siblings of patients with hereditary hemochromatosis Digestion 2001
  
• Screening for Hereditary Hemochromatosis in Siblings and Children of Affected Patients
  A Cost-Effectiveness Analysis Hashem B. El-Serag, MD, MPH; John M. Inadomi, MD; and Kris V. Kowdley, MD Annals of Internal Medicine, 15 February 2000 Volume 132 Number 4,  HFE gene testing for the C282Y mutation is a cost-effective method of screening relatives of patients with hereditary hemochromatosis.

• Screening Newborns for Genetic Disease Helps Parents By Anne Harding NEW YORK (Reuters Health) -Dec. 7, 2000  Screening newborns for hemochromatosis is effective, practical, and can save their parents' lives, according to French researchers who have developed a program for identifying infants with this common and potentially fatal genetic disease.  [no longer available online]

• The Answer to Crib Death  “Sudden Infant Death Syndrome” (SIDS) 
  Joseph G. Hattersley From Journal of Orthomolecular Medicine Volume 8, Number 4, 1993, pp.229-245  2.3 The role of iron in crib death has been almost universally ignored. Some have found excess iron in SID autopsies. Ferritin is a strong oxidant; an excess promotes oxidation reactions.
  
• Use of HFE Mutation Analysis for Hereditary Hemochromatosis:  The Need for Physician Education in the Translation of Basic Science to Clinical Practice  Manish Kohli, MB, ChB, Steven A. Schichman, MD, PhD, Louis Fink, MD, Clive S. Zent, MB, BCh, Department of Internal Medicine, Division of Hematology/Oncology and the Department of Pathology, John L. McClellan Memorial Veteran's Hospital and University of Arkansas for Medical Sciences, Little Rock.  Southern Medical Journal 

• Why concentration of serum ferritin does not in all circumstances reflect storage iron but is still of value in its estimation.  Rajantie J, Siimes MA. We describe a 10-year-old girl with familial haemochromatosis which is associated with a normal concentration of S-ferritin, myocardial disease and diabetes mellitus. We speculate that iron is accumulated primarily in the heart and pancreas as such isoferritins are not detected by the routine assay of serum ferritin based on antispleen or placenta ferritin.
  
• Zellweger Syndrome Information Page  
  National Institute of Neurological Disorders and Stroke   The most common features of Zellweger syndrome include an enlarged liver, high levels of iron and copper in the blood, and vision disturbances.

Links specific to Neonatal Hemochromatosis [NH]

• Acute liver failure in infancy: A 14-year experience of a pediatric liver transplantation center 
  J Pediatr 2001 Dec  We conclude that ALF during the first year of life is a severe condition with poor prognosis, despite the advent of liver transplantation.
  

• Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary hemochromatosis Parkkila S, Waheed A, Britton RS, Bacon BR, Zhou XY, Tomatsu S, Fleming RE, Sly WS The Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, MO 63104, USA Proc Natl Acad Sci U S A 1997 Nov 25. These studies place the normal HFE protein at the site of contact with the maternal circulation where its association with transferrin receptor raises the possibility that the HFE protein plays some role in determining maternal/fetal iron homeostasis.

• Congenital generalized infantile myofibromatosis and neonatal hemochromatosis. An autopsy case report.   Turk J Pediatr.   2000 Oct-Dec   In addition to infantile myofibromatosis, neonatal hemochromatosis characterized by iron deposition in parenchymatous organs such as liver, pancreas, lungs, thyroid, and adrenal glands was another important characteristic of the case.

• Diagnosis of neonatal hemochromatosis with MR imaging and duplex Doppler sonography   Publication Date 11/23/1999  With the help of MRI, plus increasing awareness of the disorder, diagnosis is now often made early, even in utero. Duplex Doppler sonography does not provide information on siderosis but shows abnormalities in the liver or blood-flow patterns associated with liver disease.
  

• IDIOPATHIC NEONATAL HEMOCHROMATOSIS OMIM entry

• Infant thrives on dad’s big liver graft  
  RANCHO MIRAGE, Calif.- Despite a 24-to-1 size mismatch, a father’s donated liver lobe is doing fine 15 months after transplant to his month-old daughter. Physicians Weekly, August 1999

• Information on NH at the American Hemochromatosis Society's website.  Includes excellent information by AHS pediatric medical advistory council member, Dr. Alex Knisely. 

• Inherited iron overload.  
  Acta Paediatr Scand Suppl. 1989 Several inherited forms of iron overload have been described. It is now accepted that HC, usually regarded as a disease of adult life, is an inherited disorder, hence all first degree relatives must be presumed to be at increased risk of developing iron overload and the diagnosis is now frequently made in young relatives. The combination of serum iron, transferrin saturation and serum ferritin determination will detect iron overload in an early, precirrhotic stage
  

• Iron-overload disease in infants involving fetal growth retardation, lactic acidosis, liver haemosiderosis, and aminoaciduria.  Fellman V, Rapola J, Pihko H, Varilo T, Raivio KO Lancet 1998 Feb 14;351(9101):490-3
  

• Iron storage disease in parents and sibs of infants with neonatal hemochromatosis: 30-year follow-up.  Dalhoj J, Kiaer H, Wiggers P, Grady RW, Jones RL, Knisely AS Am J Med Genet 1990 Nov;37(3):342-5 These findings suggest that first-degree relatives of persons with NH are not necessarily at increased risk of iron storage disease in later life.

• Juvenile idiopathic haemochromatosis: a life-threatening disorder presenting as hypogonadotropic hypogonadism.   Hum Genet 1983  We describe here four cases of idiopathic haemochromatosis having onset of symptoms before or around the age of 20 years.  These subjects may have a history of unexplained abdominal pain, present with hypogonadotropic hypogonadism, and, unless proper treatment is started, die early because of cardiac dysfunction.

• Neonatal hemochromatosis  Tidsskr Nor Laegeforen. 1998 Feb 28  With the help of MRI and salivary gland biopsies, plus increasing awareness of this disorder, the diagnosis is now often made quite early, and successful liver transplantations have been reported.

• Neonatal hemochromatosis: significance of early identification Acta Biomed Ateneo Parmense. 2000.   We report two sisters with neonatal hemochromatosis with different outcome.

• Neonatal (perinatal) hemochromatosis.  Elleder M, Chlumska A, Hadravska S, Pilat D  Cesk Patol 2001 Nov;37(4):146-53  Autopsy findings are described of six cases (from four families) of neonatal hemochromatosis, a defect featured by severe prenatal iron storage in the liver and in a number of visceral organs similarly as in the hereditary adult-type hemochromatosis.

Links specific to JUVENILE HEMOCHROMATOSIS [JH]

Research currently suggests that JH & HH are separate conditions of iron overload, with JH not being connected to the HFE related iron overload.  I am not personally convinced that this is the case.  In my opinion, much more research into iron overload in children needs done to prove this to be true.

• Hemochromatosis:  Genetics, Pathophysiology, Diagnosis and Treatment, "Introduction to Hemochromatosis"  Part I,  by Barton & Edwards.  Except from their book, [a pdf file] This is a large & excellent book covering all areas of hemochromatosis.  Published in 2000, $225.00

• Hereditary juvenile haemochromatosis: a genetically heterogeneous life-threatening iron-storage disease.  QJM 1998 Sep;  We report four patients (two of each sex) from three pedigrees affected by juvenile haemochromatosis with a mean onset at 22 years (range 14-30). All had endocrine deficiency with postpubertal gonadal failure secondary to pituitary disease; two suffered near-fatal cardiomyopathy with heart failure.

• Inherited iron overload.  
  Acta Paediatr Scand Suppl. 1989 Several inherited forms of iron overload have been described. It is now accepted that HC, usually regarded as a disease of adult life, is an inherited disorder, hence all first degree relatives must be presumed to be at increased risk of developing iron overload and the diagnosis is now frequently made in young relatives. The combination of serum iron, transferrin saturation and serum ferritin determination will detect iron overload in an early, precirrhotic stage

 

• Juvenile haemochromatosis.
   Baillieres Clin Gastroenterol 1998 Jun Early diagnosis of JH is important to avoid cardiac complications which can lead to premature death. As with HFE-linked disease, JH is responsive to phlebotomies.

• Juvenile hemochromatosis (JH) OMIM entry  Iron accumulation begins early in life and causes clinical symptoms before the age of 30 years. JH is a more severe disease.

• Successful pregnancy following gonadotropin therapy in a young female with juvenile idiopathic hemochromatosis and secondary hypogonadotropic hypogonadism 
  Haematologica 1995 Jul-Aug; Heart failure and hypogonadotropic hypogonadism are the most frequent clinical problems encountered in patients with juvenile idiopathic hemochromatosis.

  ---

Should a pregnant woman routinely be given prenatal vitamins with iron?  Many women who have been diagnosed with HH recall that many of their HH problems began with their pregnancies.  Perhaps it could be attributed to the iron that they were ingesting for 9 months?  A midwife that I once worked with supported my "theory" that pregnancy induced hypertension [PIH,] preeclampsia, gestational diabetes & other problems in pregnancy may be related to IO and/or undiagnosed HH.  Hopefully, someday there will be studies done to see if there is indeed a connection.

Links specific to pregnancy

• Classification and diagnosis of iron overload 
  Haematologica 1998 May The recent description of new conditions associated with iron overload and the identification of the genetic defect of hereditary hemochromatosis prompted us to review this subject and to redefine the diagnostic criteria of iron overload disorders. [mentions placenta absorptin of iron.]

• IRON/PRETERM DELIVERY
  SCIENCE/HEALTH ABSTRACTS Volume 14, Number 4, Copyright 1995, Phylis A. Austin Pregnant women with high serum ferritin concentrations are at increased risk of early preterm spontaneous delivery, according to a report from the Departments of Nutrition Sciences and Obstetrics and Gynecology at the University of Alabama at Birmingham. They concluded that serum ferritin levels can be used to predict early preterm delivery. (American Journal of Clinical Nutrition 61(4)911, April 1995)

• Iron—Too Much of a Good Thing? Archived Articles: 12-04-2000 Steven Bratman, M.D.   A new study suggests that too much iron can cause problems of its own in pregnancy. An evaluation of 488 pregnant women found that very high levels of iron are also associated with pre-term delivery and low-birthweight infants, as well as other complications.

• Maternal hemoglobin concentration during pregnancy and risk of stillbirth.
  JAMA. 2000 Nov 22-29 High hemoglobin concentration at first measurement during antenatal care appears to be associated with increased risk of stillbirth, especially preterm and SGA antepartum stillbirths.
  

• Safety aspects of iron in food. 
  Ann Nutr Metab 2001;  There is no regulated iron excretion in overload. Excess of pharmaceutical iron may cause toxicity and therapeutic doses may cause gastrointestinal side effects.

• Successful pregnancy following gonadotropin therapy in a young female with juvenile idiopathic hemochromatosis and secondary hypogonadotropic hypogonadism 
  Haematologica 1995 Jul-Aug; Heart failure and hypogonadotropic hypogonadism are the most frequent clinical problems encountered in patients with juvenile idiopathic hemochromatosis.

• THE ADVERSE EFFECTS OF ZINC DEFICIENCY  
  A review from the literature by Tuula E. Tuormaa for FORESIGHT, the Association for the Promotion of Preconceptual Care  [first published in: Journal of Orthomolecular Medicine, 10 (3 & 4): 149-164, (1995)

• The Answer to Crib Death  “Sudden Infant Death Syndrome” (SIDS) 
  Joseph G. Hattersley From Journal of Orthomolecular Medicine Volume 8, Number 4, 1993, pp.229-245  2.3 The role of iron in crib death has been almost universally ignored. Some have found excess iron in SID autopsies. Ferritin is a strong oxidant; an excess promotes oxidation reactions. Giving supplemental iron during lactation, or formula “with iron,” can precipitate one avoidable form of SID. Suppose a baby contracts botulism (Clostridium botulinum). If it lives on its mother’s milk alone botulism develops slowly, the baby can be brought to the hospital and treated successfully. If the baby gets formula “with iron,” botulism strikes like lightning. In 69 botulism cases, 39 had been breast- and 30 formula-fed. The ten who died were all formula babies getting added iron. ⁴⁰

Back to the "Munnsters" main Hemochromatosis page