Hemochromatosis (HFE) gene mutations and response to chloroquine in porphyria cutanea tarda.
نویسندگان
چکیده
OBJECTIVE To examine the role of hemochromatosis (HFE) gene mutations, which are associated with porphyria cutanea tarda (PCT), in the therapeutic response to chloroquine. DESIGN We retrospectively analyzed a database (Excel version 2001 [Microsoft Excel, Redmond, Wash]; date range of search, 1985-1999) of chloroquine-treated patients with PCT on whether HFE mutations (C282Y and H63D) might have influenced the clinical response, urinary porphyrin excretion, liver enzyme activities, and serum iron markers. Serum samples and corresponding complete sets of data before and after therapy were available in 62 of 207 patients with PCT who were treated exclusively with chloroquine. SETTINGS Academic teaching hospital. INTERVENTION For treatment, low-dose chloroquine diphosphate, 125 to 250 mg twice weekly, was used during a median time of 16 months (range, 12-26 months). RESULTS Of the 62 German patients with PCT, 37 (60%) carries HFE mutations. Chloroquine therapy was accompanied by clinical remission and reduced urinary porphyrin excretion (P<.001) in the 24 patients (39%) with HFE wild type as well as in 35 HFE heterozygous patients with PCT (56%). Decreases of serum iron markers following chloroquine therapy were limited to patients with PCT and HFE wild type. All patients homozygous for the C282Y mutation (3 [5%] of 62) had high serum iron, ferritin, and transferrin saturation and failed to respond to chloroquine treatment. CONCLUSIONS The therapeutic response to chloroquine was not compromised by C282Y heterozygosity and compound heterozygosity of HFE mutations. Because HFE C282Y homozygotes (+/+) did not respond to chloroquine and a decrease in serum iron concentration was limited to patients with PCT and HFE wild type, phlebotomy should be first-line therapy in patients with PCT and HFE mutations.
منابع مشابه
Precipitating factors of porphyria cutanea tarda in Brazil with emphasis on hemochromatosis gene (HFE) mutations. Study of 60 patients*
BACKGROUND Porphyria cutanea tarda is the most common form of porphyria, characterized by the decreased activity of the uroporphyrinogen decarboxylase enzyme. Several reports associated HFE gene mutations of hereditary hemochromatosis with porphyria cutanea tarda worldwide, although up to date only one study has been conducted in Brazil. OBJECTIVES Investigation of porphyria cutanea tarda ass...
متن کاملHaemochromatosis gene mutations and response to chloroquine in sporadic porphyria cutanea tarda.
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Down-regulation of hepcidin in porphyria cutanea tarda.
Hepatic siderosis is common in patients with porphyria cutanea tarda (PCT). Mutations in the hereditary hemochromatosis (hh) gene (HFE) explain the siderosis in approximately 20% patients, suggesting that the remaining occurrences result from additional genetic and environmental factors. Two genes known to modify iron loading in hh are hepcidin (HAMP) and hemojuvelin (HJV). To determine if muta...
متن کاملHemochromatosis gene sequence deviations in German patients with porphyria cutanea tarda.
Patients with porphyria cutanea tarda (PCT) reveal a susceptibility to reversible inactivation of hepatic uroporphyrinogen decarboxylase, which might be triggered by alcohol, hepatitis C virus infection, and iron overload. Inherited factors that may predispose to clinically overt PCT also include sequence deviations in the HFE gene that is mutated in classical hemochromatosis. Here, we studied ...
متن کاملPorphyria cutanea tarda: effects and risk factors for hepatotoxicity from high-dose chloroquine treatment.
High-dose chloroquine therapy for porphyria cutanea tarda is rarely used now because of its hepatic side-effects. The mechanisms of the effects and side-effects are poorly understood. We describe here effects, side-effects and long-term follow-up in 57 patients with a first-time diagnosis of porphyria cutanea tarda treated with 1-3 phlebotomies followed by 250 mg chloroquine phosphate daily for...
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ورودعنوان ژورنال:
- Archives of dermatology
دوره 139 3 شماره
صفحات -
تاریخ انتشار 2003