Northwestern Medicine McHenry Hospital McHenry, IL
Introduction: Hereditary hemochromatosis (HH) is an autosomal recessive that usually affects middle-aged people [1]. In most patients, homozygous C282Y mutations in the HFE gene express the disease. But in some occurrences, compound heterozygous, including C282Y and H63D mutations, were also witnessed. We present an atypical case where heterozygous H63D manifested as HH in an 89-year-old man.
Case Description/Methods: An 89-year-old Caucasian man of Italian descent presented with confusion, left-sided facial droop, and slurring of speech. Past medical history included end-stage renal disease on hemodialysis and atrial fibrillation. For the past few months before presentation, the patient has been complaining of increasingly tired with intermittent episodes of slurring speech, mainly after he receives dialysis.
During the initial physical examination, the patient had confusion but was alert & oriented to self and time. There was mild abdominal distension and positive for asterixis, and the skin was bronze in color. Initial labs showed in table 1. The patient had persistent hypoglycemia and required intravenous glucose administration. Brain imaging was normal. CT scan of the abdomen, pelvis, and chest showed severe cardiomegaly and a moderate amount of ascites. Iron studies were abnormal. Ascites fluid analysis was consistent with cirrhosis. Although, an ultrasound right upper quadrant was negative for any cirrhotic morphology. MRI showed hemosiderosis. 2D Echo showed a severely dilated right ventricle. The patient empirically underwent two sessions of phlebotomy. Genetic testing confirmed heterozygous H63D mutation. The patient followed up for the phlebotomy sessions and demonstrated significant improvement.
Discussion: This case highlights the consideration of HH in differential regardless of age if a patient presents with symptoms suspected of HH. Standard genetic testing includes testing C282Y and H63D mutations in the HFE gene on chromosome 6. Less frequently tested S65C, HFE4, TFR2-HHC, and FTH1 gene mutations also have the expression of HH in sporadic cases [2-3]. Previously, heterozygous C282Y carriers with iron overload are assumed to have other genetic changes or influence by environmental factors, such as alcohol or liver disease, that increase disease expression [2]. However, no such literature is available for heterozygous H63D carriers. Given the unusual age for phenotype expression and atypical disease, the presentation makes this unique case for learning the pathophysiology and genetics of HH.
