Case at a Glance
Juvenile hemochromatosis, or hereditary hemochromatosis type 2A, is a rare autosomal recessive disorder driven by mutations in the HJV gene. The condition causes severe systemic iron overload with multiorgan involvement, frequently affecting endocrine and skeletal health. This case describes a 32-year-old woman who presented with secondary amenorrhea, progressive skin hyperpigmentation, arthritis, and poorly controlled diabetes, ultimately leading to a diagnosis of HJV-related iron overload with multisystem consequences.
Clinical Presentation and Key Features
The patient reported several years of amenorrhea and new skin darkening, alongside joint pains and escalating insulin requirements for diabetes. Physical examination revealed signs consistent with iron overload, including skin hyperpigmentation. Endocrine testing demonstrated hypogonadotropic hypogonadism, contributing to her amenorrhea. Notably, there was evidence of osteoporosis on bone density testing, with lumbar spine T-score −3.3 and femoral neck T-score −3.7, highlighting compromised skeletal health at a young age.
Diagnostic Workup
Laboratory studies showed striking iron metrics: ferritin above 2000 ng/mL and transferrin saturation of 93.8%, indicating severe iron overload. The combination of endocrine dysfunction, early-onset osteoporosis, and systemic iron deposition prompted imaging and genetic assessment. Magnetic resonance imaging revealed iron deposition in the pituitary gland, liver, pancreas, and heart, consistent with multiorgan iron overload. Genetic testing confirmed a pathogenic homozygous mutation in HJV (c.1063G > T, p.Asp355Tyr), establishing the diagnosis of hereditary hemochromatosis type 2A.
Pathophysiology and Implications
HJV mutations disrupt hepcidin regulation, leading to unchecked intestinal iron absorption and rapid, extensive iron accumulation. The pituitary, liver, pancreas, and heart are particularly vulnerable, which explains the observed hypogonadism, diabetes, and cardiac concerns in affected individuals. Skeletal involvement—osteoporosis and fragility—often accompanies hormonal disturbances and iron toxicity. Early recognition is crucial, as irreversible organ damage can occur if treatment is delayed.
Treatment and Multidisciplinary Management
The patient underwent weekly therapeutic phlebotomy with the goal of achieving a ferritin target near 50 ng/mL, a critical step in limiting ongoing iron deposition and organ injury. Glycemic control was addressed with a basal-bolus insulin regimen, reflecting the pancreatic involvement and diabetes risk in juvenile hemochromatosis. Endocrine therapy included estrogen-progestin hormone replacement to address hypogonadism and preserve secondary sexual characteristics. Calcium and vitamin D supplementation were added to mitigate osteoporosis risk. A multidisciplinary team—endocrinology, hematology, gynecology, and nutrition—collaborated to tailor therapy and monitor adverse effects.
Early Outcomes and Take-Home Messages
After approximately three months of treatment, the patient experienced notable improvement: cutaneous hyperpigmentation lightened, hemoglobin A1c decreased from 8.5% to 7.8%, ferritin levels fell to 1294 ng/mL, and menstrual cycles resumed, signaling partial reversal of some iron-related sequelae. While organ damage may not be fully reversible, early and aggressive management in juvenile hemochromatosis can significantly improve quality of life and long-term prognosis.
Clinical Significance
This case underscores the importance of considering juvenile hemochromatosis in young patients with unexplained hypogonadism, diabetes, or osteoporosis. Given the rapid iron accumulation and potential for multiorgan involvement, prompt diagnostic workup and initiation of phlebotomy are essential. Genetic confirmation of HJV mutations not only guides therapy but also informs family counseling and screening strategies for at-risk relatives.
Conclusion for Clinicians
Hereditary hemochromatosis type 2A should feature in the differential diagnosis when young patients present with hypogonadism, diabetes, or early osteoporosis. A comprehensive, multidisciplinary approach that combines phlebotomy, endocrine management, and bone health strategies can arrest disease progression and yield meaningful gains in endocrine and metabolic control.
