Isolated hyperferritinemia with normal transferrin saturation and dysmetabolism, in the absence of the two known mutations in the HFE gene of hereditary hemochromatosis.

Isolated hyperferritinemia with normal transferrin saturation and dysmetabolism, in the absence of the two known mutations in the HFE gene of hereditary hemochromatosis Sir, We report on a patient who had isolated hyperfer-ritinemia with normal transferrin saturation, dysme-tabolism, and mild hepatic iron overload. He was negative for the two known mutations in the HFE gene of hereditary hemochromatosis. Other factors that could induce hyperferritinemia with normal transferrin saturation were excluded. A brother with normal iron parameters was heterozygous for the Cys282Tyr mutation in the HFE gene. The physiopathologic mechanism of the association of unexplained hyperferritine-mia with dysmetabolism, described by others as a syndrome , is still unknown. This disorder should be considered in the differential diagnosis of hyperferritine-mic states. The association of elevated serum ferritin levels with high serum iron level and increased transferrin saturation is highly suggestive of hereditary hemo-chromatosis (HH). Elevated serum ferritin values without high transferrin saturation should be considered with caution, and hepatocellular necrosis, chronic inflammatory disorders, or malignancies should be investigated. In addition, two hyperfer-ritinemic conditions have recently been reported: 1) the " hereditary hyperferritinemia-cataract syndrome " (HHCS) caused by a mutation in the iron-responsive element (IRE) of the ferritin L-subunit gene. In this autosomal dominant disorder patients have normal iron status and early-onset congenital cataracts; 1-4 and 2) a non HLA-linked syndrome described by Moirand et al. in 1997, 5 in which an isolated hyper-ferritinemia is associated with mild to moderate iron overload and common metabolic disorders, such as diabetes, hyperlipidemia, obesity, and hypertension. We report on a patient who presented with isolated hyperferritinemia, normal transferrin saturation, mild iron overload, and common metabolic disorders. He was negative for the known mutations of HH. One of the two proband's brothers was het-erozygous for the Cys282Tyr mutation in the HFE gene (Figure 1). The proband (arrowed in Figure 1), a 55-year-old man of Italian origin, was referred to our institution because of monoclonal IgG␭ gammopathy and hyperferritinemia. Both abnormalities had been found incidentally one year earlier (IgG␭ 1.2 g/dL; serum fer-ritin 1,727 µg/L). At admission, the patient was overweight (92 kg). He had hypertension (150/90 mm Hg) and was on treatment with oral antidiabetic therapy because of abnormal glucose metabolism (fasting serum glucose 145 mg/dL). Alcohol abuse was excluded. At physical examination, liver enlargement was present (2 cm below the costal margin). Serum ferritin value was markedly increased (2,650 µg/L), while serum iron (115 µg/dL) and …