Iron Study is a Weak Indicator in Symptomatic C282Y/ H63D Compound Heterozygotes

Wael Toama Almaan El

doi:10.4172/2167-7921.1000153

Abstract

Hemochromatosis is a metabolic disease with protean manifestations including polyarthritis. It is often under diagnosed due to poor classification criteria, ambiguity in laboratory testing and the inability to obtain a histological diagnosis. The current DNA testing for hemochromatosis may not adequately identify patients at risk for indolent chronic migratory arthropathy secondary to this condition. In this case, we present a patient with compound heterozygotes of hemochromatosis laboratory testing, indolent chronic migratory polyarthritis, generalized weakness, depression and abnormal iron studies. Our subject presented to medical attention with a four-year history of indolent chronic migratory polyarthritis resulting in multiple orthopedic surgeries including right shoulder replacement and left ankle fusion. The patient?s laboratory results including Complete Blood Count (CBC) and Comprehensive Metabolic Panel (CMP) showed mild elevated liver enzymes and transferrin saturation percentage. Iron studies demonstrated mild elevation in ferritin value, but returned to normal limits with oral steroid and NSAID treatments. A thorough serologic work-up for rheumatic, immunologic and infectious diseases were within normal limits. Physical examination revealed thickening and tenderness of the meta-carpophalangeal joints. The distribution of joint involvement prompted further testing for secondary causes of polyarthritis such as hemochromatosis. Genetic testing for hemochromatosis identified the C282Y and H63D alleles of the HFE gene. The variable range of iron studies in patients with compound heterozygotes portends iron studies alone as a weak indicator of probability of the disease. Laboratory testing in classical hemochromatosis is typically associated with, elevated iron studies, elevated ferritin and transferrin saturation in addition to abnormal liver associated enzymes depending upon the duration and severity of the disease. This standard laboratory studies may not be sensitive enough to identify patients with hemochromatosis with or without associated polyarthritis early in their disease course.

Highlights

The most common mutations of the HFE gene involved in Hereditary Hemochromatosis (HH) are C282Y and H63D
The clinical presentation of hemochromatosis was associated in 85 to 90 percent of cases with homozygosity for the C282Y mutation of HFE gene which is known as classical hemochromatosis, but clinical hemochromatosis presents in a small portion of cases with compound heterozygotes
The typical clinical manifestations of iron overload seen in homozygous HH appear to be quite uncommon in patients who are compound heterozygotes for HH [10,11] even in cases have serum transferrin saturation values that is compatible with homozygous HH [10]

Summary

Introduction

The most common mutations of the HFE gene involved in Hereditary Hemochromatosis (HH) are C282Y and H63D. The triad of Hemochromatosis diagnosis, which includes clinical symptoms, abnormal iron studies and confirmed genetic tests, has avoided many liver biopsies. A 47-year-old male presented with intermittent polyarthritis including wrists, low back, shoulders, hips, and knees with morning stiffness His symptoms started gradually during the last 4 years have prompted orthopedic surgeries to include right shoulder replacement and left ankle fusion. The patient’s laboratory results were all, except iron studies, unremarkable and included the following: hemoglobin 15.6 g/dl, hematocrit 46.3%, PLT 213 K/μL, WBC 7.7 K/μL, basic metabolic panel ,urinalysis, Lyme disease titers, ANA, rheumatoid factor, anti-CCP, RPR, HLA-B27, TSH,homocysteine, B12, and folic acid His inflammatory markers, ESR and CRP, were elevated but returned to normal limits with oral steroid and NSAID treatments. Genetic testing for hemochromatosis identified the C282Y and H63D alleles of the HFE gene

Findings

Discussion

Conclusion