Juvenile hemochromatosis is a rare genetic disorder defined by excessive iron accumulation in the body’s tissues and organs. Its onset typically occurs before age 30, presenting a more accelerated and severe clinical course than adult-onset hemochromatosis. Because of its aggressive nature, significant organ damage can occur early in life, making timely diagnosis and intervention important. The disorder affects males and females equally.
Genetic Causes and Inheritance
Juvenile hemochromatosis is an inherited condition from mutations in genes that regulate iron metabolism. Most cases are caused by mutations in the hemojuvelin (HJV) gene, while a smaller percentage arise from mutations in the hepcidin (HAMP) gene. Both genes are involved with hepcidin, the primary hormone regulating iron absorption and distribution in the body.
The inheritance pattern for this condition is autosomal recessive. This means an individual must inherit a mutated copy of the responsible gene from both parents to develop juvenile hemochromatosis. Individuals who inherit only one mutated gene are carriers; they typically do not develop the disease but can pass the mutation to their children. This genetic basis is distinct from adult hemochromatosis, which is associated with mutations in the HFE gene.
Mutations in either the HJV or HAMP gene lead to a severe deficiency of functional hepcidin. Without sufficient hepcidin to control it, the body absorbs an excessive amount of iron from the diet. This uncontrolled uptake results in a progressive and toxic buildup in various organs, initiating the damage that characterizes the disease.
Signs and Symptoms
The initial symptoms of juvenile hemochromatosis can be nonspecific, including fatigue and joint pain, which may appear during the first decade of life. As iron continues to accumulate, more distinct and serious complications develop, directly related to organ-specific damage.
One of the most prominent features is endocrine system disruption, particularly hypogonadotropic hypogonadism. This condition results from iron deposition in the pituitary gland, which impairs its function and reduces sex hormone production. In young adults, this can cause delayed puberty, decreased libido, and infertility. Iron damage to the pancreas also leads to a higher incidence of diabetes.
Cardiac complications are a hallmark of the disease and represent the leading cause of death in untreated individuals. Iron accumulation in the heart muscle leads to cardiomyopathy (a weakening of the heart) and arrhythmias (irregular heartbeats). These conditions can progress rapidly, causing heart failure. Liver involvement is also common, with iron overload causing inflammation that can advance to fibrosis, cirrhosis, and an increased risk of liver cancer.
The Diagnostic Process
Diagnosis begins with blood tests that reveal abnormalities in iron metabolism. Physicians measure transferrin saturation, which indicates the percentage of iron-transporting protein saturated with iron, and serum ferritin, which reflects the total iron stored in the body. In juvenile hemochromatosis, both of these levels are significantly elevated.
While blood tests are strong indicators, a definitive diagnosis requires genetic testing. This identifies the specific mutations in the HJV or HAMP genes responsible for the disorder. Confirming the genetic basis differentiates juvenile hemochromatosis from other forms of iron overload and guides management strategies.
Medical imaging also plays a part in assessing the extent of organ damage. A magnetic resonance imaging (MRI) technique known as T2-weighted imaging is particularly useful. This non-invasive scan can accurately measure iron concentrations in specific organs, most notably the liver and the heart. This allows doctors to quantify the severity of the iron deposition and monitor treatment effectiveness. In some cases, a liver biopsy may be performed to examine a small tissue sample.
Treatment and Management
The primary treatment for juvenile hemochromatosis is aggressive and frequent phlebotomy, the therapeutic removal of blood. Each unit of blood removed extracts a significant amount of iron from the body. Due to the rapid rate of iron accumulation, phlebotomy sessions are often required weekly for an extended period, sometimes for up to two or three years, to bring iron levels down to a safe range. The goal is to reduce serum ferritin to a target level of around 50 ng/mL.
Once iron levels are stabilized, patients enter a maintenance phase requiring lifelong, regular phlebotomy to prevent re-accumulation. For individuals who cannot tolerate frequent blood draws or have severe cardiac complications, iron chelation therapy may be used. This treatment involves medications that bind to iron in the bloodstream, allowing it to be excreted through urine or stool.
Management is a lifelong commitment that involves regular monitoring of iron levels and organ function. In addition to phlebotomy or chelation, treatment also addresses specific complications from organ damage. This can include hormone replacement therapy for hypogonadism, medications for heart failure or diabetes, and management of liver disease by a specialist.