Background: Hyperferritinemia is a nonspecific laboratory abnormality that is associated with true iron overload in approximately 10% of cases. Most frequently, it reflects an acute phase response secondary to underlying inflammatory, infectious, or neoplastic conditions. Hereditary Hyperferritinemia-Cataract Syndrome (HHCS) is a rare cause (~1 in 200,000), resulting from an autosomal dominant mutation in the FTL gene, which encodes L-ferritin. This mutation leads to dysregulated overproduction of L-ferritin, which accumulates in the ocular lens and causes early-onset bilateral cataracts. Notably, iron overload is absent in this condition.Case Presentation Summary: A 2-year-old female with a medical history of autism spectrum disorder, chronic constipation, and vesicoureteral reflux was referred by her primary care physician to the emergency department due to marked hyperferritinemia (ferritin: 1330 ng/mL) identified during an evaluation for pallor. Repeat testing confirmed elevated ferritin (1197 ng/mL) without biochemical or clinical evidence of iron overload. Chest radiography and abdominal ultrasonography were unremarkable. Signs and symptoms such as skin hyperpigmentation, arthralgia, arthritis, or recurrent infections were absent.Hyperferritinemia (1000–2000 ng/mL) was persistent over time, with normal complete blood count, iron studies, lactate dehydrogenase, liver function tests, and C-reactive protein. Tumor markers and genetic testing for hemochromatosis mutations were negative.The patient was referred to Pediatric Hematology; family screening was performed, revealing hyperferritinemia in the father. Subsequent genetic analysis identified a heterozygous c.-168G>C mutation in the FTL gene, confirming the diagnosis of HHCS. Genetic testing of the child confirmed the same mutation. She was observed by Ophthalmology; bilateral posterior polar cataracts were identified. The patient remains under multidisciplinary follow-up.Learning Points Discussion: This case highlights the importance of following a systematic diagnostic approach to hyperferritinemia, assessing iron overload, systemic inflammatory or infectious diseases, and neoplastic disorders. In the absence of these conditions, rare genetic syndromes such as HHCS should be considered. Although uncommon, HHCS is an important differential diagnosis with a benign course: it does not result in iron deposition in parenchymal organs and does not require iron-depletion therapy. However, ophthalmologic surveillance is essential to monitor for progressive lens opacities and assess the need for surgical intervention in cases of significant visual impairment.
