Overview
Hereditary hemochromatosis type 2A, also known as juvenile hemochromatosis, is a rare autosomal recessive disorder driven by mutations in the HJV gene. It causes severe systemic iron overload with multiorgan involvement that often presents at a younger age than classic adult forms. The following case underscores how iron toxicity can manifest through endocrine and skeletal complications in a young woman, and how prompt, coordinated care can reverse or mitigate organ damage.
Case Summary
A 32-year-old woman presented with secondary amenorrhea, progressive skin hyperpigmentation, joint problems, and poorly controlled diabetes. Initial labs revealed alarmingly elevated ferritin levels (>2000 ng/mL) and a transferrin saturation of 93.8%, indicating profound iron overload. Imaging showed iron deposition in the pituitary gland, liver, pancreas, and heart, consistent with systemic iron accumulation. Genetic testing confirmed a homozygous mutation in the HJV gene (c.1063G > T, p.Asp355Tyr), establishing a diagnosis of hereditary hemochromatosis type 2A.
Endocrine and Skeletal Manifestations
The patient demonstrated hypogonadotropic hypogonadism, a common endocrinopathy in juvenile hemochromatosis resulting from iron deposition in the pituitary. This contributed to secondary amenorrhea and had implications for future fertility. Osteoporosis was identified with lumbar spine T-score of −3.3 and femoral neck T-score of −3.7, reflecting severe bone loss at a relatively young age. The combination of hypogonadism and osteoporosis highlights the systemic reach of iron toxicity beyond the liver and heart.
Additional Organ Involvement
Although not all patients present with symptomatic cardiac disease, MRI findings in this case showed iron deposition in the heart, alongside hepatic and pancreatic involvement. Pancreatic iron overload contributed to insulin deficiency and challenging glycemic control, explaining the patient’s diabetes. Cardiac iron loading raises concerns for potential arrhythmias or heart failure if left untreated, though timely therapy can prevent progression.
Management Strategy
The multidisciplinary treatment approach aimed to rapidly reduce body iron stores and stabilize organ function. Key components included:
- Therapeutic phlebotomy performed weekly with a target ferritin level around 50 ng/mL to deplete excess iron safely.
- Glycemic control with a basal-bolus insulin regimen to manage diabetes secondary to pancreatic iron deposition.
- Endocrine replacement estrogen-progestin therapy to address hypogonadism and support reproductive health, with consideration of long-term bone health management.
- Bone health optimization calcium and vitamin D supplementation, and ongoing monitoring for osteoporosis and fracture risk.
Remarkably, after three months of therapy, several outcomes improved: skin pigmentation lightened, glycated hemoglobin decreased from 8.5% to 7.8%, ferritin fell to 1294 ng/mL, and menstrual cycles resumed. These improvements illustrate the potential reversibility of some iron-related manifestations with aggressive iron reduction and comprehensive care.
Clinical Implications
This case reinforces the need for clinicians to suspect juvenile hemochromatosis in young patients who present with unexplained hypogonadism, diabetes, or osteoporosis. Early recognition is crucial because irreversible organ damage can be prevented with timely intervention. Family screening and genetic counseling may also be appropriate in confirmed cases to identify at-risk relatives and guide monitoring strategies.
Take-Home Messages
- Juvenile hemochromatosis type 2A can present with a triad of endocrine and skeletal abnormalities in young women.
- Comprehensive management combining phlebotomy, endocrine replacement, and bone and glycemic care can yield meaningful clinical improvements.
- High vigilance for iron overload in young patients with unexplained secondary amenorrhea, diabetes, or osteoporosis can enable earlier diagnosis and better outcomes.
