Iron Studies in Hemochromatosis During Pregnancy.
Authors: Sokoloff Alisa , Brook Scott , Cooper Marvin 
Published: October 2019

Abstract 5099

Hereditary hemochromatosis is usually caused by a mutation in HFE gene that regulates iron uptake from the diet. The two most common mutations in the HFE gene are the well described C282Y and H63D mutations. Homozygous inheritance of either one of these mutations as well as compound heterozygous inheritance of one of each of the mutant alleles may result in a spectrum of phenotypic variants of the disease ranging from asymptomatic to multi-organ compromise. One half of a percent of the United States population carries two copies of the mutant HFE gene therefore making hemochromatosis the most common genetically inherited disease. On average one half of these patients will develop clinically significant disease.

Usually hemochromatosis is a clinical diagnosis, however genetic testing as well as liver biopsy are utilized as confirmatory diagnostic modalities. Besides, hemochromatosis should be suspected in females with transferrin saturation over 45% and males over >50%. It is well established that in females hemochromatosis is usually identified later in life, likely secondary to menstruation, childbirth, and breastfeeding.

We hypothesized that hemochromatotic women with elevated ferritin levels at time of conception probably do not require phlebotomies during the course of their pregnancies. In addition, this patient population likely does not require iron supplementation, otherwise indicated during pregnancy and breastfeeding.

We are reporting a case of 36-year-old female found to be homozygous for C282Y mutation five months prior to becoming pregnant. This patient's transferrin saturation at the time of diagnosis was 75% and her ferritin level was 320ng/ml. Her past medical history is only significant for mitral valve prolapse. Her physical exam at the time of diagnosis was normal, except for a known II/IV systolic murmur. Although asymptomatic at presentation, this patient was found to have increased iron deposition in the liver detected with abdominal MRI. During the course of her pregnancy this patient received no iron supplementation and likewise she did not receive any phlebotomy treatments. Her iron studies were carefully monitored on average every four weeks to assess for phlebotomy or iron supplementation needs. The patient never became symptomatic from either iron overload or anemia during this pregnancy. Evidently the fetus was able to utilize maternal iron sufficiently with secondary benefit of decreasing maternal ferritin levels. Besides, despite withholding iron supplementation during pregnancy this patient did not develop a clinically significant degree of anemia. Likewise she did not develop any evidence of exacerbation of mitral valve prolapse symptoms – this complication is not uncommon during pregnancy secondary to anemia. A healthy child was delivered at term via normal vaginal delivery, with minimal complications secondary to umbilical cord enlargement without compression and a 1st degree perianal laceration with minimal blood loss. The iron panel on the child was not obtained.

Date 7/28/08 at diagnosis 12/11/08 7 weeks of gestation 1/12/09 13 weeks of gestation 1/26/09 15 weeks of gestation 2/23/09 19 weeks of gestation 3/16/09 22 weeks of gestation 4/13/09 26 weeks of gestation 5/11/09 30 weeks of gestation 6/08/09 34 weeks of gestation 7/02/09 37 weeks of gestation 7/20/09 6 days postpartum Hemoglobin/Hematocrit (g/dL/%) 14.3/40.0 13.7/38.4 12.9/36.0 12.1/34.1 11.7/33.5 11.6/34.0 13.2/36.1 13.1/36.7 12.6/35.4 13.2/37.0 13.3/38.3 Serum Iron (μg/dL) 153 169 207 214 233 260 260 247 285 287 95 TIBC (μg/dL) 203 220 217 234 243 270 311 295 295 310 307 Ferritin (ng/mL) 320 258 268 220 180 147 95 75 66 145 174 Transferrin Saturation (%) 75 77 92 91 92 93 84 92 94 93 31

Maternal ferritin levels decreased significantly during the course of this pregnancy, reaching a nadir of 66ng/mL by 34 weeks of gestation, with subsequent rise to 145ng/mL two weeks prior to delivery.

In conclusion, the favorable outcome of this case supports our stated hypothesis in at least the homozygous C282Y HFE gene mutation patient population with elevated preconception ferritin levels (to at least 320 ng/mL) and increased preconception transferrin saturations (to at least 75%). Further studies of hemochromatotic pregnant women with the aforementioned genotype (most common) as well as other hereditary hemochromatosis genotypes during both pregnancy, and breastfeeding may be warranted.

Disclosures

No relevant conflicts of interest to declare.