AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the ...AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/mL,respectively.Serum ferritin was 1716.3± 376μg/L.Liver biopsy in one patient did not show any evidence of iron overload.Serum hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/mL,respectively,while serum ferritin was 110±128.08μg/L.There was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/mL vs 15.30±15.71 ng/mL,P= 0.612)using two-tailed t-test. CONCLUSION:Serum hepcidin levels in HHCS patients is similar to that in HCs.Our study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.展开更多
To study the clinical correlates of the H63D mu-tation we have analysed the phenotype of H63D homozygotes identified through mutation analysis in a referral laboratory. A total of 366 blood samples referred for lIFE a...To study the clinical correlates of the H63D mu-tation we have analysed the phenotype of H63D homozygotes identified through mutation analysis in a referral laboratory. A total of 366 blood samples referred for lIFE analysis were screened for C282Y and H63D mutations. Four H63D homozygotes were identified. All had raised serum ferritin but normal transferrin saturation. They were negative for hepatitis B and C and only one patient consumed excess alcohol. In all 4 cases ultrasonography revealed fatty liver. In two patients a liver biopsy was done and showed mild siderosis with an unusual distribution and macrovesicular steatosis. These data confirm the association between fatty liver, hyperferritinaemia and increased hepatic iron, but do not clarify whether siderosis was related to steatosis rather than homozygosity for the H63D mutation. Patients with fatty liver may complicate the interpretation of data in population studies of the expression of H63D homozygosity.展开更多
Background: Elevated serum ferritin is more commonly due to reactive causes such as infection, hepatic disorders, rheumatologic conditions, and malignancy than true iron overload. Extreme hyperferritinemia (>10,000...Background: Elevated serum ferritin is more commonly due to reactive causes such as infection, hepatic disorders, rheumatologic conditions, and malignancy than true iron overload. Extreme hyperferritinemia (>10,000 ng/mL), on the other hand, should prompt consideration of rare conditions such as adult-onset Still’s disease (AOSD) or hemophagocytic lymphohistiocytosis. This paper aims to present the case of the highest reported extreme hyperferritinemia (actual level 256,000 ng/mL) in a patient eventually diagnosed with adult onset Still’s Disease (AOSD). Case Presentation: A 55-year-old male, Filipino, was admitted due to acute onset fever and shortness of breath. He was initially assessed to have community-acquired pneumonia and a suspect for coronavirus disease 2019 (COVID-19), hence inflammatory markers were requested. Ferritin was notably elevated at 44,255 ng/mL. He eventually tested negative for COVID-19 RT-PCR. He was investigated for other causes of markedly elevated ferritin levels. His complete blood count (CBC) only showed leukocytosis with no peripheral blasts, iron level and liver function tests were normal, HIV immunoassay was negative, ANA was 1:80 speckled with normal complement level, rheumatoid factor negative, and positron emission tomography (PET) scan revealed presence of lymphadenopathies and did not show solid tumors. He was treated for urinary tract infection and pneumonia but still had intermittent fever and increasing ferritin trend, with the highest documented level at 256,000 ng/mL. Fulfilling the Yamaguchi criteria, he was managed as a case of severe AOSD and received tocilizumab. He had lysis of fever and decreasing trend of ferritin levels thereafter, with ferritin level of 34,184 ng/mL three weeks after tocilizumab infusion. He was discharged and improved with prednisone and methotrexate as home medications. Conclusion: To our knowledge, the highest level of extreme hyperferritinemia recorded in literature as of 2016 is 143,931 ng/mL, which was associated with hematologic malignancy. This case documents the highest noted ferritin level of 256,000 ng/mL associated with AOSD. AOSD remains a diagnosis of exclusion due to its nonspecific symptoms and absence of definitive tests. The treatment comprises NSAIDs, steroids, and immunosuppressives;however biological treatments such as tocilizumab can be considered in severe cases.展开更多
Introduction. Mutations in the promoter region of ferritin light gene can induce an uncontrolled over expression of this protein. Consequently, ferritin is found in serum at very high levels (~1000 ng/mL) and it accum...Introduction. Mutations in the promoter region of ferritin light gene can induce an uncontrolled over expression of this protein. Consequently, ferritin is found in serum at very high levels (~1000 ng/mL) and it accumulates in the crystalline lens, generating cataracts. This entity is known as hyperferritin and hereditary cataract syndrome (HHCS) which is inherited in an autosomal dominant manner. Case Presentation. We describe a family affected by HHCS. The proband was identified among subjects submitted to a biological screening for hemochromatosis. He had very high levels of serum ferritin (~900 ng/mL) with normal transferrin saturation (TS). The proband has a single H63D HFE-gene mutation and normal HAMP-gene. He was submitted to periodical phlebotomies that induced anemia and a decrease in TS but no changes on serum ferritin levels. Analyses of promoter region of ferritin-light chain gene showed a 39 C > T mutation, responsible for HHCS. The proband’s sister carried also this mutation. Both subjects had developed cataracts. Discussion. Similar to the first family described carrying this syndrome and to other cases reported, the proband was erroneously submitted to phlebotomies. Clinical consequences are illustrated in this report. HHCS is an infrequent entity which has to be correctly identified. The unique therapeutic approach to this syndrome must be cataract surgery.展开更多
Herein we report a case of acute liver failure(ALF) and hemophagocytic lymphohistiocytosis(HLH) induced by varicella infection, successfully rescued by a combination therapy of acyclovir, supportive care, and immunosu...Herein we report a case of acute liver failure(ALF) and hemophagocytic lymphohistiocytosis(HLH) induced by varicella infection, successfully rescued by a combination therapy of acyclovir, supportive care, and immunosuppression with dexamethasone and etoposide. A previously healthy 16-year-old boy presented with generalized rash, fever, severe abdominal pain, and abnormal liver function within 4 d. Chickenpox was suspected, and acyclovir and intravenous immunoglobulin were started on admission. However, the patient's condition deteriorated overnight with soaring transaminases, severe coagulopathy and encephalopathy. On the fourth day of admission, pancytopenia emerged, accompanied by hypofibrinogenemia and hyperferritinemia. The patient was diagnosed with ALF. He also met the diagnostic criteria of HLH according to the HLH-2004 guideline. Polymerase chain reaction(PCR) amplifications of varicella-zoster virus(VZV) were positive, confirming that VZV was a causative trigger for ALF and HLH. In view of the devastating immune activation in HLH, immunosuppression therapy with dexamethasone and etoposide was administered, in addition to high dose acyclovir. The patient's symptoms improved dramatically and he finally made a full recovery. To our knowledge, this is only the second report of a successful rescue of ALF associated with HLH, without resorting to liver transplantation. The first case was reported in a neonate infected by herpes simplex virus-1. However, survival data in older children and adults are lacking, most of whom died or underwent liver transplantation. Our report emphasizes the clinical vigilance for the possible presence of HLH, and the necessity of extensive investigation for underlying etiologies in patients presenting with indeterminate ALF. Early initiation of specific therapy targeting the underlying etiology, and watchful immunosuppression such as dexamethasone and etoposide, together with supportive therapy, are of crucial importance in this life-threatening disorder.展开更多
BACKGROUND Macrophage activation syndrome(MAS)can be a fatal complication of rheumatic disorders,which occurs most commonly in patients with systemic juvenile idiopathic arthritis or systemic lupus erythematosus.It ha...BACKGROUND Macrophage activation syndrome(MAS)can be a fatal complication of rheumatic disorders,which occurs most commonly in patients with systemic juvenile idiopathic arthritis or systemic lupus erythematosus.It has rarely been reported in patients with dermatomyositis.Here,we describe a fatal case of MAS that developed in an adult patient with dermatomyositis.CASE SUMMARY A 44-year-old woman was admitted to our hospital with fever,generalized rash and muscle weakness.Fifteen days later,the fever persisted after the use of antibiotics,and repeat blood culture was negative.The patient then exhibited a typical Gottron sign and diffuse erythema on the face and neck,which were consistent with a diagnosis of dermatomyositis.The patient exhibited limb muscle strength of 2,and electromyography was suggestive of muscle-derived damage,which also supported a diagnosis of dermatomyositis.In addition,the patient exhibited high serum ferritin level,cytopenia,liver dysfunction,coagulopathy,enlarged spleen and hypertriglyceridemia,all of which are typical manifestations of MAS.The patient was diagnosed with dermatomyositis complicated by MAS.Although a high dose of methylprednisolone was administered for 15 d,the patient’s condition continued to deteriorate and central nervous system symptoms developed.Eventually,treatment was discontinued,and the patient died.CONCLUSION MAS is an important,potentially fatal,complication of dermatomyositis.Although MAS is rare in dermatomyositis,it should be considered in the differential diagnosis of an unexplained change of hemoglobin,platelet,fibrinogen,ferritin and triglyceride,which may complicate dermatomyositis.展开更多
基金Supported by Research and Development Department,Ealing Hospital NHS Trust,Uxbridge Road,Southall,London,UB13HW,United Kingdom
文摘AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/mL,respectively.Serum ferritin was 1716.3± 376μg/L.Liver biopsy in one patient did not show any evidence of iron overload.Serum hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/mL,respectively,while serum ferritin was 110±128.08μg/L.There was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/mL vs 15.30±15.71 ng/mL,P= 0.612)using two-tailed t-test. CONCLUSION:Serum hepcidin levels in HHCS patients is similar to that in HCs.Our study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.
基金Supported by the European Commission Fifth Framework Programme Grant No. QLK6-CT-1999-02237. GS was supported by a Clinical Fellowship from the European Commission (Leonardo da Vinci Grant I/99/2/09209/PL/II. 1.2.a/FPI)
文摘To study the clinical correlates of the H63D mu-tation we have analysed the phenotype of H63D homozygotes identified through mutation analysis in a referral laboratory. A total of 366 blood samples referred for lIFE analysis were screened for C282Y and H63D mutations. Four H63D homozygotes were identified. All had raised serum ferritin but normal transferrin saturation. They were negative for hepatitis B and C and only one patient consumed excess alcohol. In all 4 cases ultrasonography revealed fatty liver. In two patients a liver biopsy was done and showed mild siderosis with an unusual distribution and macrovesicular steatosis. These data confirm the association between fatty liver, hyperferritinaemia and increased hepatic iron, but do not clarify whether siderosis was related to steatosis rather than homozygosity for the H63D mutation. Patients with fatty liver may complicate the interpretation of data in population studies of the expression of H63D homozygosity.
文摘Background: Elevated serum ferritin is more commonly due to reactive causes such as infection, hepatic disorders, rheumatologic conditions, and malignancy than true iron overload. Extreme hyperferritinemia (>10,000 ng/mL), on the other hand, should prompt consideration of rare conditions such as adult-onset Still’s disease (AOSD) or hemophagocytic lymphohistiocytosis. This paper aims to present the case of the highest reported extreme hyperferritinemia (actual level 256,000 ng/mL) in a patient eventually diagnosed with adult onset Still’s Disease (AOSD). Case Presentation: A 55-year-old male, Filipino, was admitted due to acute onset fever and shortness of breath. He was initially assessed to have community-acquired pneumonia and a suspect for coronavirus disease 2019 (COVID-19), hence inflammatory markers were requested. Ferritin was notably elevated at 44,255 ng/mL. He eventually tested negative for COVID-19 RT-PCR. He was investigated for other causes of markedly elevated ferritin levels. His complete blood count (CBC) only showed leukocytosis with no peripheral blasts, iron level and liver function tests were normal, HIV immunoassay was negative, ANA was 1:80 speckled with normal complement level, rheumatoid factor negative, and positron emission tomography (PET) scan revealed presence of lymphadenopathies and did not show solid tumors. He was treated for urinary tract infection and pneumonia but still had intermittent fever and increasing ferritin trend, with the highest documented level at 256,000 ng/mL. Fulfilling the Yamaguchi criteria, he was managed as a case of severe AOSD and received tocilizumab. He had lysis of fever and decreasing trend of ferritin levels thereafter, with ferritin level of 34,184 ng/mL three weeks after tocilizumab infusion. He was discharged and improved with prednisone and methotrexate as home medications. Conclusion: To our knowledge, the highest level of extreme hyperferritinemia recorded in literature as of 2016 is 143,931 ng/mL, which was associated with hematologic malignancy. This case documents the highest noted ferritin level of 256,000 ng/mL associated with AOSD. AOSD remains a diagnosis of exclusion due to its nonspecific symptoms and absence of definitive tests. The treatment comprises NSAIDs, steroids, and immunosuppressives;however biological treatments such as tocilizumab can be considered in severe cases.
文摘Introduction. Mutations in the promoter region of ferritin light gene can induce an uncontrolled over expression of this protein. Consequently, ferritin is found in serum at very high levels (~1000 ng/mL) and it accumulates in the crystalline lens, generating cataracts. This entity is known as hyperferritin and hereditary cataract syndrome (HHCS) which is inherited in an autosomal dominant manner. Case Presentation. We describe a family affected by HHCS. The proband was identified among subjects submitted to a biological screening for hemochromatosis. He had very high levels of serum ferritin (~900 ng/mL) with normal transferrin saturation (TS). The proband has a single H63D HFE-gene mutation and normal HAMP-gene. He was submitted to periodical phlebotomies that induced anemia and a decrease in TS but no changes on serum ferritin levels. Analyses of promoter region of ferritin-light chain gene showed a 39 C > T mutation, responsible for HHCS. The proband’s sister carried also this mutation. Both subjects had developed cataracts. Discussion. Similar to the first family described carrying this syndrome and to other cases reported, the proband was erroneously submitted to phlebotomies. Clinical consequences are illustrated in this report. HHCS is an infrequent entity which has to be correctly identified. The unique therapeutic approach to this syndrome must be cataract surgery.
基金Supported by Capital Characteristic Clinic Project,No.Z161100000516045
文摘Herein we report a case of acute liver failure(ALF) and hemophagocytic lymphohistiocytosis(HLH) induced by varicella infection, successfully rescued by a combination therapy of acyclovir, supportive care, and immunosuppression with dexamethasone and etoposide. A previously healthy 16-year-old boy presented with generalized rash, fever, severe abdominal pain, and abnormal liver function within 4 d. Chickenpox was suspected, and acyclovir and intravenous immunoglobulin were started on admission. However, the patient's condition deteriorated overnight with soaring transaminases, severe coagulopathy and encephalopathy. On the fourth day of admission, pancytopenia emerged, accompanied by hypofibrinogenemia and hyperferritinemia. The patient was diagnosed with ALF. He also met the diagnostic criteria of HLH according to the HLH-2004 guideline. Polymerase chain reaction(PCR) amplifications of varicella-zoster virus(VZV) were positive, confirming that VZV was a causative trigger for ALF and HLH. In view of the devastating immune activation in HLH, immunosuppression therapy with dexamethasone and etoposide was administered, in addition to high dose acyclovir. The patient's symptoms improved dramatically and he finally made a full recovery. To our knowledge, this is only the second report of a successful rescue of ALF associated with HLH, without resorting to liver transplantation. The first case was reported in a neonate infected by herpes simplex virus-1. However, survival data in older children and adults are lacking, most of whom died or underwent liver transplantation. Our report emphasizes the clinical vigilance for the possible presence of HLH, and the necessity of extensive investigation for underlying etiologies in patients presenting with indeterminate ALF. Early initiation of specific therapy targeting the underlying etiology, and watchful immunosuppression such as dexamethasone and etoposide, together with supportive therapy, are of crucial importance in this life-threatening disorder.
文摘BACKGROUND Macrophage activation syndrome(MAS)can be a fatal complication of rheumatic disorders,which occurs most commonly in patients with systemic juvenile idiopathic arthritis or systemic lupus erythematosus.It has rarely been reported in patients with dermatomyositis.Here,we describe a fatal case of MAS that developed in an adult patient with dermatomyositis.CASE SUMMARY A 44-year-old woman was admitted to our hospital with fever,generalized rash and muscle weakness.Fifteen days later,the fever persisted after the use of antibiotics,and repeat blood culture was negative.The patient then exhibited a typical Gottron sign and diffuse erythema on the face and neck,which were consistent with a diagnosis of dermatomyositis.The patient exhibited limb muscle strength of 2,and electromyography was suggestive of muscle-derived damage,which also supported a diagnosis of dermatomyositis.In addition,the patient exhibited high serum ferritin level,cytopenia,liver dysfunction,coagulopathy,enlarged spleen and hypertriglyceridemia,all of which are typical manifestations of MAS.The patient was diagnosed with dermatomyositis complicated by MAS.Although a high dose of methylprednisolone was administered for 15 d,the patient’s condition continued to deteriorate and central nervous system symptoms developed.Eventually,treatment was discontinued,and the patient died.CONCLUSION MAS is an important,potentially fatal,complication of dermatomyositis.Although MAS is rare in dermatomyositis,it should be considered in the differential diagnosis of an unexplained change of hemoglobin,platelet,fibrinogen,ferritin and triglyceride,which may complicate dermatomyositis.
