遗传性球形红细胞增多症合并肝内胆汁淤积致严重高胆红血症1例

<正>遗传性球形细胞增多症(Hereditary spherocytosis,HS)是一种常染色体显性遗传性疾病,临床上主要表现为溶血性贫血伴黄疸,以间接胆红素升高为主,很少合并肝内胆汁淤积和极度的高胆红素血症。我们报道1例罕见的遗传性球形细胞增多症伴有直接胆红素极度升高和肝内胆汁淤积患者,对疾病进程中一些特殊的临床表现发生的原因进行了分析。1病例摘要患者女性,49岁,会计。因反复腹痛伴尿黄皮肤黄40天于2013年10月10日入院。缘于2013年8月29日无明     

遗传性球形红细胞增多症合并重度肝内胆汁淤积和继发性血色病

一、病例资料病例1:男性患者,23岁.主因眼黄16年,加重伴皮肤黄染1月余于2008年6月27日10:00入院.患者缘于16年前无明显诱因出现眼黄,无恶心、呕吐、腹胀、腹泻、于当地医院查肝功能异常,应用保肝药物1个月后停药.     

No elevation of serum gamma-glutamyl transpeptidase level in a polymyositis case with intrahepatic cholestasis

A 57-year-old male with polymyositis developed jaundice which was induced by intrahepatic cholestasis. During his course before and after discontinuation of the administration of an anabolic steroid hormone which was suspected as the possible agent, serum gamma-glutamyl transpeptidase (gamma-GTP) levels were consistently within normal level, although serum levels of bilirubin, A1-P and LAP were elevated. Difference in the levels among biliary tract enzymes was discussed with regard to the mechanism of elevation of serum biliary tract enzyme levels, and a possible significance of the examination of bile juice was suggested.     

Diminished extractable spectrin in the erythrocytes of a patient with 'sporadic' hereditary spherocytosis

A 51-year-old white man of Irish extraction was found to have apparent 'sporadic' hereditary spherocytosis with a reticulocyte count of 6%. Twelve of his 13 siblings were examined and found to be haematologically normal. The patient's erythrocytes were found to have a diminished amount of spectrin as compared to his siblings and to unrelated controls. It is suggested that the proband may represent either a new mutant or possibly double heterozygosity for two inherited biochemical variants of the red cell membrane skeleton which individually give no haematological abnormalities.     

Massive hemothorax due to intrathoracic extramedullary hematopoiesis in a patient with hereditary spherocytosis

 Extramedullary hematopoiesis (EMH) is a rare disorder, characterized by the appearance of hematopoietic elements outside of the bone marrow, which occurs in patients with chronic myeloproliferative disorders or congenital hemolytic anemias. We report on a 64-year-old man with hereditary spherocytosis, who presented with anemia, jaundice, intrathoracic EMH, and massive hemothorax. The diagnosis of EMH was established after computer tomography (CT)-guided punctuation of the paravertebral mass. The patient underwent splenectomy and thoracic drainage. After 1 year, the patient is in good health, with normal hemoglobin values, and hemothorax has not recurred. Received: 23 December 1999 / Accepted: 31 May 2000     

Extreme hyperbilirubinemia in a patient with hereditary spherocytosis, Gilbert's syndrome, and obstructive jaundice

Hyperbilirubinemia may be of several etiologies in the individual patient. An 18-year-old man presented with extreme hyperbilirubinemia (direct bilirubin 23.0 mg/dl, total bilirubin 60.0 mg/dl), hepatosplenomegaly, and anemia. Hematologic studies prelaparotomy documented the presence of hereditary spherocytosis. Intraoperative liver biopsy revealed moderately reduced levels of glucuronyl transferase activity (Gilbert's syndrome). Common bile duct obstruction secondary to choledocholithiasis was found, and a cholecystectomy and splenectomy were performed. This case stresses the potential confusion among several diseases which may present with hyperbilirubinemia.     

Novel mutation in a Chinese patient with progressive familial intrahepatic cholestasis type 3

Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T(p.L59L) mutation in exon 4, c.504C>T(p.N168N) mutation in exon 6, c.711A>T(p.I237I) mutation in exon 8, c.874A>T(p.K292X) in exon 9 and a novel mutation, c.1804G>T(p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602 W in exon 15 was predicted as probably damaging by Poly Phen-2 with a score of 0.986(sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.     

Pregnancy in patients with hereditary spherocytosis

The influence of pregnancy on the course of hereditary spherocytosis was investigated in 21 women during their 44 pregnancies. Fourteen pregnancies were followed up directly, 30 were evaluated from anamnestic data. In the majority of investigated women with hereditary spherocytosis pregnancy caused no problems. When complications developed, they were not serious as a rule. Only about one third of pregnancies in non-splenectomized women developed anaemia or anaemia deteriorated. In the latter enhanced haemolysis participated. In splenectomized patients the incidence of complaints was minimal.     

Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy

Progressive familial intrahepatic cholestasis (PFIC) type 1, 2 and 3 are due to mutations in ATP8B1, ABCB11 and ABCB4, respectively. Each of these genes encodes a hepatocanalicular transporter, which is essential for the proper formation of bile. Mutations in ABCB4 can result in progressive cholestatic disease, while mutations in ATP8B1 and ABCB11 can result both in episodic cholestasis, referred to as benign recurrent intrahepatic cholestasis (BRIC) type 1 and 2, as well as in progressive cholestatic disease. This suggests a clinical continuum and these diseases are therefore preferably referred to as ATP8B1 deficiency and ABCB11 deficiency. Similarly PFIC type 3 is designated as ABCB4 deficiency. Heterozygous mutations in each of these transporters can also be associated with intrahepatic cholestasis of pregnancy. This review summarizes the pathophysiology, clinical features and current as well as future therapeutic options for progressive familial- and benign recurrent intrahepatic cholestasis as well as intrahepatic cholestasis of pregnancy.     

Inherited protein C deficiency,protein S deficiency and hyperhomocysteineaemia in a patient with hereditary spherocytosis

We report a family with hereditary spherocytosis in whom there is, in addition, a cluster of genetic predispositions to thrombosis. Although inherited prothrombotic abnormalities are prevalent in the general population, the likelihood of this combination of abnormalities being found in a single family is extremely low. The management of such high risk individuals is discussed.     

Inherited protein C deficiency, protein S deficiency and hyperhomocysteinaemia in a patient with hereditary spherocytosis.

We report a family with hereditary spherocytosis in whom there is, in addition, a cluster of genetic predispositions to thrombosis. Although inherited prothrombotic abnormalities are prevalent in the general population, the likelihood of this combination of abnormalities being found in a single family is extremely low. The management of such high risk individuals is discussed.     

Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5‐year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.     

Inhibition of erythropoiesis by human parvovirus-containing serum from a patient with hereditary spherocytosis in aplastic crisis

Aplastic phase serum from a patient with aplastic crisis of hereditary spherocytosis, which was demonstrated to contain human parvovirus, inhibited in vitro erythroid colony formation almost completely. Human parvovirus was resistant to heating for 30 min at 56 degrees C. The suppressive effect of the serum was completely abrogated by adding convalescent phase serum from another patient with aplastic crisis of hereditary spherocytosis. Some normal sera had similar neutralizing ability. The results suggested that aplastic crisis of a patient with hereditary spherocytosis is caused by human parvovirus and that the neutralizing test could offer a tool for predicting the future occurrence of aplastic crisis in the patients with chronic hemolytic anemia.     

Stuttering priapism associated with hereditary spherocytosis

Stuttering priapism is a clinical phenomenon that occurs commonly in certain patient populations, including sickle cell anemia and other hematologic dyscrasias. Although the mechanism is still not completely understood, treatment is focused on prevention of recurrence in the outpatient setting, and immediate detumescence and minimizing corporal fibrosis in the acute setting. We present a case of stuttering priapism in a 44 year-old male with hereditary spherocytosis and discuss the pathophysiology and clinical management of this entity.