BACKGROUND:Acute intermittent porphyria (AIP) is the most common hepatic porphyria.Its clinical presentation includes severe disabling and life-threatening neurovisceral symptoms and acute psychiatric symptoms.These s...BACKGROUND:Acute intermittent porphyria (AIP) is the most common hepatic porphyria.Its clinical presentation includes severe disabling and life-threatening neurovisceral symptoms and acute psychiatric symptoms.These symptoms result from the overproduction and accumulation of porphyrin precursors,5-aminoleuvulinic acid (ALA) and porphobilinogen (PBG).The effect of medical treatment is transient and is not effective once irreversible neurological damage has occurred.Liver transplantation (LT) replaces hepatic enzymes and can restore normal excretion of ALA and PBG and prevent acute attacks.METHOD:Two cases of LT for AIP were identified retrospectively from a prospectively maintained LT database.RESULT:LT was successful with resolution of AIP in two patients who suffered from repeated acute attacks.CONCLUSION:LT can correct the underlying metabolic abnormality in AIP and improves quality of life significantly.展开更多
BACKGROUND Acute intermittent porphyria(AIP)is a rare autosomal dominant porphyrin metabolic disease caused by a mutation in the hydroxymethylbilane synthase(HMBS)gene.This study aimed to explore the clinical manifest...BACKGROUND Acute intermittent porphyria(AIP)is a rare autosomal dominant porphyrin metabolic disease caused by a mutation in the hydroxymethylbilane synthase(HMBS)gene.This study aimed to explore the clinical manifestations of a patient with AIP,to identify a novel HMBS gene mutation in the proband and some of her family members,and to confirm the pathogenicity of the variant.CASE SUMMARY A 22-year-old Chinese woman developed severe abdominal pain,lumbago,sinus tachycardia,epileptic seizure,hypertension,and weakness in lower limbs in March,2018.Biochemical examinations indicated hypohepatia and hyponatremia.Her last menstrual period was 45 d prior to admission,and she was unaware of the pregnancy,which was confirmed by a pregnancy test after admission.Sunlight exposure of her urine sample for 1 h turned it from yellow to wine red.Urinary porphyrin test result was positive.Based on these clinical manifestations,AIP was diagnosed.After increasing her daily glucose intake(250–300 g/d),abdominal pain was partially relieved.Three days after hospitalization,spontaneous vaginal bleeding occurred,which was confirmed as spontaneous abortion;thereafter,her clinical symptoms completely resolved.Genetic testing revealed a novel heterozygous splicing variant of the HMBS gene in exon 10(c.648_651+1delCCAGG)in the proband and four other family members.The pathogenicity of the variant was verified through bioinformatic methods and a minigene assay.CONCLUSION We identified a novel HMBS gene mutation in a Chinese patient with AIP and confirmed its pathogenicity.展开更多
BACKGROUND Acute intermittent porphyria(AIP)is an inherited disorder of porphyrin metabolism with a worldwide distribution and a prevalence ranging from 1 to 9 per million population.AIP is caused by an autosomal domi...BACKGROUND Acute intermittent porphyria(AIP)is an inherited disorder of porphyrin metabolism with a worldwide distribution and a prevalence ranging from 1 to 9 per million population.AIP is caused by an autosomal dominant-inherited mutation of low penetrance resulting in a deficiency of porphobilinogen deaminase(PBGD)activity.Acute attacks are provoked by stressors such as certain medications,alcohol,and infection.We herein present the first case report of AIP detected in a post-renal transplant patient.CASE SUMMARY The patient was a 65-year-old man who underwent transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephropathy.He subsequently developed diabetes mellitus which required insulin therapy.He had been treated in the recent past with local mesalamine for proctitis.He presented with classic but common symptoms of AIP including intense abdominal pain,hypertension,and anxiety.He had multiple visits to the emergency room over a 6-mo period for these same symptoms before the diagnosis of AIP was entertained.His urinary postprandial blood glucose level was 60 mg/24 h(normal,<2 mg/24 h).He was placed on a high carbohydrate diet,and his symptoms slowly improved.CONCLUSION This case report describes a common presentation of an uncommon disease,in which post-transplant complications and medications may have contributed to precipitating the previously undiagnosed AIP.We hypothesize that the lowcarbohydrate diet and insulin with which our patient was treated may have led to the attacks of AIP.Alternatively,our patient’s mesalamine treatment for proctitis may have led to an acute AIP crisis.A high index of suspicion is needed to consider the diagnosis of a heme synthesis disorder,which presents with the common symptoms of abdominal pain,high blood pressure,and anxiety.展开更多
There is a strong association between porphyria cutanea tarda (PCT) and chronic viral hepatitis C. Therapy for chronic viral hepatitis C may improve PCT. However, there are only a few reports of the de novo developmen...There is a strong association between porphyria cutanea tarda (PCT) and chronic viral hepatitis C. Therapy for chronic viral hepatitis C may improve PCT. However, there are only a few reports of the de novo development of PCT during therapy for chronic viral hepatitis C. We describe the development of PCT in a 56-year-old patient with chronic viral hepatitis C after 12 wk of peginterferon/ribavirin therapy. In addition, the patient was homozygous for the H63D hereditary hemochromatosis gene (HFE ) mutation. The association of PCT with chronic viral hepatitis C and the possible role of hepatic iron overload and ribavirin-induced hemolytic anemia in the development of PCT during therapy for chronic viral hepatitis C are discussed.展开更多
· Porphyria cutanea tarda(PCT) with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these.Amniot...· Porphyria cutanea tarda(PCT) with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these.Amniotic membrane grafting had been performed in their patient suffering from porphyria eye disease, but necrosis developed in the grafts. Nevertheless, in our patient, allogeneic corneoscleral limbus transplantation prevented necrosis from development at corneoscleral limbus. So we considered that the allogeneic corneoscleral limbus transplantation might be an option to repair the necrosis in porphyria eye disease with avoiding sunlight and using artificial tear drops.展开更多
Liver fibrosis and cirrhosis are predisposing factors for the development of hepatocellular carcinoma (HCC). Hemosiderosis has also been described to trigger carcinogenesis. A significant iron overload, as found in he...Liver fibrosis and cirrhosis are predisposing factors for the development of hepatocellular carcinoma (HCC). Hemosiderosis has also been described to trigger carcinogenesis. A significant iron overload, as found in hereditary hemochromatosis (HHC), is a risk factor for HCC and may also promote the symptoms of porphyria cutanea tarda (PCT). A 68-year old male patient presented to our clinic with a suspected HCC, elevated alpha-fetoprotein but normal liver function tests. He reported a 25 year-old history of vitiligo upon exposure to sunlight. The patient underwent an extended left hemihepatectomy, and the recovery was uneventful, with the exception of a persistent hyperbilirubinemia. Perfusion problems and extrahepatic cholestasis were ruled out by CT-scan with angiography and MR-cholangiopancreatography. However, MRI showed an iron overload. Histology confirmed the HCC (pT3, pN0, G3, R0) and revealed a portal fibrosis and hemosiderosis. Based on the skin lesions we suspected a PCT that was confirmed by laboratory tests showing elevated porphyrin, uroporphyrin, coproporphyrin and porphobilinogen. Concurrently, molecular diagnostics revealed homozygosity for the C282Y mutation within the hemochromatosis HFE gene. After phlebotomy and normalization of liver function tests the patient was discharged. This is the first case ever showing the unusual combination of HCC in a fibrotic liver with HHC and PCT. This diagnosis not only warrants oncological follow-up but also symptomatic therapy to normalize iron metabolism and thereby improve liver function and alleviate the symptoms of HHC and PCT. Thus progression of fibrosis may be prevented and liver regeneration supported.展开更多
High-sensitivity detection of porphyrin in blood is very important for the early diagnosis and treatment of porphyria.Based on the advantages of longer luminescence lifetime and lower background interference,organic a...High-sensitivity detection of porphyrin in blood is very important for the early diagnosis and treatment of porphyria.Based on the advantages of longer luminescence lifetime and lower background interference,organic afterglow molecular porphyrin detection probes were developed,but these probes show poor water solubility and insufficient luminescence intensity.Herein,we present an afterglow nanoprobe(Eu-NP)for porphyria detection in whole blood.The luminescent substance(europium complex)and the organic vinyl co mpound reacted with singlet oxygen(^(1)O_(2))were selected for encapsulation in polystyrene spheres.Eu-NP can respond to^(1)O_(2)produced by porphyrins,and the detection signals can be obtained by the emission of the afterglow Eu^(3+)-emissive nanosensor.Eu-NP can achieve high-sensitivity detection of porphyrin,and the lowest detection limit reaches 0.29μmol/L.The porphyrin detection in whole blood samples is consistent with clinical diagnosis results.Compared with the organic afterglow molecule,the Eu-NPs constructed in this work show a higher signal-to-noise ratio and sensitivity of porphyria detection.展开更多
Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive condition that has been reported in humansand in some animals, in which uroporphyrin 1 is deposited in the bones, teeth and urine, resulting in p...Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive condition that has been reported in humansand in some animals, in which uroporphyrin 1 is deposited in the bones, teeth and urine, resulting in pink colorationand fluorescence of the tissues and urine under long-wave ultraviolet (UV) light. We observed red teeth in nine of450 canefield rats (Rattus sordidus) captured in a small, isolated patch of sugarcane in Tully, north Queensland,Australia. The skeletons of these animals were excised and were found to be bright red under normal day light.Under UV light, the skeleton had a bright red fluorescence. It is plausible that the canefield rat population in thisisolated patch of sugarcane is small and inbreeding might have occurred, resulting in incidences of the autosomalrecessive genes that cause CEP. The canefield rat can be used as an animal model for research into porphyria.展开更多
INTRODUCTION Acute intermittent porphyria (AIP) is an autosomal dominant inborn error of metabolism caused by deficiency of porphobilinogen (PBG) deaminase,also known as hydroxymethylbilane synthase (HMBS),the third e...INTRODUCTION Acute intermittent porphyria (AIP) is an autosomal dominant inborn error of metabolism caused by deficiency of porphobilinogen (PBG) deaminase,also known as hydroxymethylbilane synthase (HMBS),the third enzyme in the heme biosynthetic pathway.The clinical features of AIP are attributed to heme depletion and accumulation of heme intermediates PBG and aminolevulinic acid (ALA),proximal to the defect.[1] Multiple organ systems can be affected in patients with AIP.The typical porphyria attacks are characterized by gastrointestinal symptoms,sympathetic overactivity,neurologic manifestations,and psychological symptoms.展开更多
文摘BACKGROUND:Acute intermittent porphyria (AIP) is the most common hepatic porphyria.Its clinical presentation includes severe disabling and life-threatening neurovisceral symptoms and acute psychiatric symptoms.These symptoms result from the overproduction and accumulation of porphyrin precursors,5-aminoleuvulinic acid (ALA) and porphobilinogen (PBG).The effect of medical treatment is transient and is not effective once irreversible neurological damage has occurred.Liver transplantation (LT) replaces hepatic enzymes and can restore normal excretion of ALA and PBG and prevent acute attacks.METHOD:Two cases of LT for AIP were identified retrospectively from a prospectively maintained LT database.RESULT:LT was successful with resolution of AIP in two patients who suffered from repeated acute attacks.CONCLUSION:LT can correct the underlying metabolic abnormality in AIP and improves quality of life significantly.
文摘BACKGROUND Acute intermittent porphyria(AIP)is a rare autosomal dominant porphyrin metabolic disease caused by a mutation in the hydroxymethylbilane synthase(HMBS)gene.This study aimed to explore the clinical manifestations of a patient with AIP,to identify a novel HMBS gene mutation in the proband and some of her family members,and to confirm the pathogenicity of the variant.CASE SUMMARY A 22-year-old Chinese woman developed severe abdominal pain,lumbago,sinus tachycardia,epileptic seizure,hypertension,and weakness in lower limbs in March,2018.Biochemical examinations indicated hypohepatia and hyponatremia.Her last menstrual period was 45 d prior to admission,and she was unaware of the pregnancy,which was confirmed by a pregnancy test after admission.Sunlight exposure of her urine sample for 1 h turned it from yellow to wine red.Urinary porphyrin test result was positive.Based on these clinical manifestations,AIP was diagnosed.After increasing her daily glucose intake(250–300 g/d),abdominal pain was partially relieved.Three days after hospitalization,spontaneous vaginal bleeding occurred,which was confirmed as spontaneous abortion;thereafter,her clinical symptoms completely resolved.Genetic testing revealed a novel heterozygous splicing variant of the HMBS gene in exon 10(c.648_651+1delCCAGG)in the proband and four other family members.The pathogenicity of the variant was verified through bioinformatic methods and a minigene assay.CONCLUSION We identified a novel HMBS gene mutation in a Chinese patient with AIP and confirmed its pathogenicity.
文摘BACKGROUND Acute intermittent porphyria(AIP)is an inherited disorder of porphyrin metabolism with a worldwide distribution and a prevalence ranging from 1 to 9 per million population.AIP is caused by an autosomal dominant-inherited mutation of low penetrance resulting in a deficiency of porphobilinogen deaminase(PBGD)activity.Acute attacks are provoked by stressors such as certain medications,alcohol,and infection.We herein present the first case report of AIP detected in a post-renal transplant patient.CASE SUMMARY The patient was a 65-year-old man who underwent transplantation 2 years previously for suspected nephroangiosclerosis and chronic interstitial nephropathy.He subsequently developed diabetes mellitus which required insulin therapy.He had been treated in the recent past with local mesalamine for proctitis.He presented with classic but common symptoms of AIP including intense abdominal pain,hypertension,and anxiety.He had multiple visits to the emergency room over a 6-mo period for these same symptoms before the diagnosis of AIP was entertained.His urinary postprandial blood glucose level was 60 mg/24 h(normal,<2 mg/24 h).He was placed on a high carbohydrate diet,and his symptoms slowly improved.CONCLUSION This case report describes a common presentation of an uncommon disease,in which post-transplant complications and medications may have contributed to precipitating the previously undiagnosed AIP.We hypothesize that the lowcarbohydrate diet and insulin with which our patient was treated may have led to the attacks of AIP.Alternatively,our patient’s mesalamine treatment for proctitis may have led to an acute AIP crisis.A high index of suspicion is needed to consider the diagnosis of a heme synthesis disorder,which presents with the common symptoms of abdominal pain,high blood pressure,and anxiety.
文摘There is a strong association between porphyria cutanea tarda (PCT) and chronic viral hepatitis C. Therapy for chronic viral hepatitis C may improve PCT. However, there are only a few reports of the de novo development of PCT during therapy for chronic viral hepatitis C. We describe the development of PCT in a 56-year-old patient with chronic viral hepatitis C after 12 wk of peginterferon/ribavirin therapy. In addition, the patient was homozygous for the H63D hereditary hemochromatosis gene (HFE ) mutation. The association of PCT with chronic viral hepatitis C and the possible role of hepatic iron overload and ribavirin-induced hemolytic anemia in the development of PCT during therapy for chronic viral hepatitis C are discussed.
文摘· Porphyria cutanea tarda(PCT) with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these.Amniotic membrane grafting had been performed in their patient suffering from porphyria eye disease, but necrosis developed in the grafts. Nevertheless, in our patient, allogeneic corneoscleral limbus transplantation prevented necrosis from development at corneoscleral limbus. So we considered that the allogeneic corneoscleral limbus transplantation might be an option to repair the necrosis in porphyria eye disease with avoiding sunlight and using artificial tear drops.
文摘Liver fibrosis and cirrhosis are predisposing factors for the development of hepatocellular carcinoma (HCC). Hemosiderosis has also been described to trigger carcinogenesis. A significant iron overload, as found in hereditary hemochromatosis (HHC), is a risk factor for HCC and may also promote the symptoms of porphyria cutanea tarda (PCT). A 68-year old male patient presented to our clinic with a suspected HCC, elevated alpha-fetoprotein but normal liver function tests. He reported a 25 year-old history of vitiligo upon exposure to sunlight. The patient underwent an extended left hemihepatectomy, and the recovery was uneventful, with the exception of a persistent hyperbilirubinemia. Perfusion problems and extrahepatic cholestasis were ruled out by CT-scan with angiography and MR-cholangiopancreatography. However, MRI showed an iron overload. Histology confirmed the HCC (pT3, pN0, G3, R0) and revealed a portal fibrosis and hemosiderosis. Based on the skin lesions we suspected a PCT that was confirmed by laboratory tests showing elevated porphyrin, uroporphyrin, coproporphyrin and porphobilinogen. Concurrently, molecular diagnostics revealed homozygosity for the C282Y mutation within the hemochromatosis HFE gene. After phlebotomy and normalization of liver function tests the patient was discharged. This is the first case ever showing the unusual combination of HCC in a fibrotic liver with HHC and PCT. This diagnosis not only warrants oncological follow-up but also symptomatic therapy to normalize iron metabolism and thereby improve liver function and alleviate the symptoms of HHC and PCT. Thus progression of fibrosis may be prevented and liver regeneration supported.
基金Project supported by the National Key R&D Program of China(2017YFA0205100)the National Natural Science Foundation of china(2193700321874027)。
文摘High-sensitivity detection of porphyrin in blood is very important for the early diagnosis and treatment of porphyria.Based on the advantages of longer luminescence lifetime and lower background interference,organic afterglow molecular porphyrin detection probes were developed,but these probes show poor water solubility and insufficient luminescence intensity.Herein,we present an afterglow nanoprobe(Eu-NP)for porphyria detection in whole blood.The luminescent substance(europium complex)and the organic vinyl co mpound reacted with singlet oxygen(^(1)O_(2))were selected for encapsulation in polystyrene spheres.Eu-NP can respond to^(1)O_(2)produced by porphyrins,and the detection signals can be obtained by the emission of the afterglow Eu^(3+)-emissive nanosensor.Eu-NP can achieve high-sensitivity detection of porphyrin,and the lowest detection limit reaches 0.29μmol/L.The porphyrin detection in whole blood samples is consistent with clinical diagnosis results.Compared with the organic afterglow molecule,the Eu-NPs constructed in this work show a higher signal-to-noise ratio and sensitivity of porphyria detection.
文摘Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive condition that has been reported in humansand in some animals, in which uroporphyrin 1 is deposited in the bones, teeth and urine, resulting in pink colorationand fluorescence of the tissues and urine under long-wave ultraviolet (UV) light. We observed red teeth in nine of450 canefield rats (Rattus sordidus) captured in a small, isolated patch of sugarcane in Tully, north Queensland,Australia. The skeletons of these animals were excised and were found to be bright red under normal day light.Under UV light, the skeleton had a bright red fluorescence. It is plausible that the canefield rat population in thisisolated patch of sugarcane is small and inbreeding might have occurred, resulting in incidences of the autosomalrecessive genes that cause CEP. The canefield rat can be used as an animal model for research into porphyria.
文摘INTRODUCTION Acute intermittent porphyria (AIP) is an autosomal dominant inborn error of metabolism caused by deficiency of porphobilinogen (PBG) deaminase,also known as hydroxymethylbilane synthase (HMBS),the third enzyme in the heme biosynthetic pathway.The clinical features of AIP are attributed to heme depletion and accumulation of heme intermediates PBG and aminolevulinic acid (ALA),proximal to the defect.[1] Multiple organ systems can be affected in patients with AIP.The typical porphyria attacks are characterized by gastrointestinal symptoms,sympathetic overactivity,neurologic manifestations,and psychological symptoms.
