Niemann-Pick type C disease

A 4-year-old Afghan girl born to consanguineous parents presented with progressive neurological regression and hepatomegaly noticed after one year of age.The child had hypotonia, repeated unexplained falls and facial dyskinesia. Bone marrow examination revealed presence of storage cells suggestive of Gauchers or Niemann Pick. Confirmatory study by lysosomal enzyme from leucocytes was normal for beta-Glucosidase and sphingomyelinase specific for Gauchers and Niemann Pick type A or B respectively. Further study was carried out on cultured skin fibroblasts in lipid deficient medium using filipin stain which showed presence of dark punctate granules confirming the diagnosis of Neimann-Pick type C, a rare autosomal recessive disorder.     

Kawasaki disease in monozygotic twins

Multiple lines of evidence suggest that susceptibility to Kawasaki disease (KD) is influenced by host genetics. Subclinical coronary artery vasculitis may be present in monozygotic twins who are discordant for clinical signs of KD. Health care providers should consider laboratory testing and echocardiography in both monozygotic twins when only one twin presents with clinical KD.     

Tetralogy of Fallot in monozygotic twins]

The causative mechanisms of congenital heart defects remain unclear and little is known about the respective implication of chance, genetics and environment, though recent findings in molecular biology may provide further insight into understanding the pathophysiologic basis of congenital heart diseases. CASE REPORT: We report the exceptional but significant case of monozygotic twins both affected by tetralogy of Fallot, for whom prenatal diagnosis ruled out 22q11 microdeletion. CONCLUSION: We discuss how far this observation is consistent with the latest hypothesis, which emphasizes the leading role of genetic factors. Several genes indeed, either separately or in combination, could be responsible for those defects, even if other influences may still come into play.     

Prenatal revelation of Niemann-Pick disease type C in siblings

OBJECTIVES: To report two cases of prenatal Niemann-Pick disease type C in siblings, with different prenatal semiology and postnatal outcome. CASE REPORTS: First fetus presented at 22 weeks'gestation with ascites, hepatosplenomegaly, then polyhydramnios. At birth, the infant developed severe cholestasis and died at day 5. His brother presented at 22 weeks'gestation an isolated hepatomegaly with cholestasis at birth showing favourable evolution. In first case, diagnosis of Niemann-Pick disease was confirmed by autopsy findings, biochemical tests on cultured skin fibroblasts and ascites fluid, then by molecular screening of NPC1 gene. Brother's molecular prenatal diagnosis was made at 14 weeks' gestation on cultured trophoblasts. CONCLUSION: Prenatal screening of this disease is particularly indicated in case of fetal ascites with hypoferritinaemia. Tests on amniotic or ascites fluid cells allow to characterize the biochemical phenotype, leading to search for molecular abnormalities. Despite the same mutation identified in siblings, disease evolution is variable, which underlines complexity of genetic counselling.     

Discordant manifestation of celiac disease in monozygotic twins

A monozygous pair of twins with discordant presentation of coeliac disease is reported. The gluten-sensitive enteropathy in one of the twins might have been initiated by a virus infection.     

A fatal respiratory form of type C Niemann-Pick disease

An unusual case of Niemann-Pick disease type C is reported. The disease was first manifested in utero with hepatomegaly and ascitis. At the age of 3 months, respiratory signs were noted due to diffuse alveolar and interstitial pneumonia. Both bronchoalveolar lavage and blood serologic studies revealed respiratory infection by respiratory syncitial virus and Chlamydia trachomatis. These concomitant infections delayed the diagnosis of Niemann-Pick disease which was finally made by the electronic microscopic studies of liver biopsy and bone marrow specimens. Type C was identified by biochemical characterization of lipid accumulation in hepatocytes and by lipid enzyme profiles obtained from cutaneous fibroblast cultures. The child died at the age of 6 months from respiratory failure. Post mortem examination of the lung showed the presence of numerous overloaded alveolar macrophages in the alveolar spaces and walls. The severity of the lung issue disease is unusual in type C Niemann-Pick disease, in which neurologic involvement is usually the main prognosis factor.     

Niemann-Pick disease type C: analysis of 7 patients

Background  

Niemann-Pick disease type C (NP-C), derived from mutation of the NPC1 or NPC2 gene, is one of the recessive lysosomal lipid storage disorders that are difficult to diagnose and treat. Since NP-C has been rarely reported in China, we reviewed 7 patients with NP-C.     

尼曼匹克病C型诊疗新进展

尼曼匹克病C型(NPC)是一种常染色体隐性遗传的溶酶体脂质贮积病, 主要累及内脏器官和神经系统, 自婴幼儿至成人均可发病, 儿童期多见。新生儿期持续存在的胆汁淤积性黄疸、脾脏肿大、猝倒发作和垂直性核上性眼肌麻痹为该病的特征性表现, 因发病年龄不同, 首发的神经系统症状不一致, 临床有明显的异质性。NPC基因缺陷导致游离胆固醇转运障碍, 在细胞内大量沉积是疾病的始发因素, 细胞的自噬功能障碍、钙稳态失平衡、氧化应激等均参与疾病的病理生理过程。通过皮肤成纤维细胞培养发现异常沉积的游离胆固醇或行基因检查发现NPC的致病性突变可确诊该病。美格鲁特是唯一被批准上市的特效药物, 早期应用可以改善神经系统症状和延缓疾病的进展。     

基因诊断C型尼曼-匹克病一例

患儿,男,11岁,智力减退伴运动障碍4年、反复下呼吸道感染2年.患儿自7岁开始出现智力减退、语言倒退、学习困难、感情易变、步态不稳、共济失调、震颤及吞咽困难,未予特殊治疗.上述症状进行性加重,并出现惊厥,表现为全身强直阵挛性发作.自2年前开始出现反复下呼吸道感染.既往史及家族史:患儿为一胎一产,足月顺产,出生时体检正常,母乳喂养,生后曾出现一过性黄疸,未予特殊治疗,自然消退.发病前体格发育和智力发育正常.父母非近亲婚配,家族史无特殊记载.     

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目的分析C型尼曼-匹克病(NPC)临床特征、诊断及治疗方法。方法总结中南大学湘雅医院2006年1月至2010年4月收治的4例NPC患儿的临床表现、实验室资料及治疗情况。结果 4例起病年龄6个月至10岁。首发症状为步态不稳2例,吐字不清1例,脾大1例。就诊时主要症状为内脏受累和锥体外系症状。骨髓细胞学检查发现典型尼曼-匹克细胞和海蓝细胞各2例。4例均予低脂饮食、多种维生素等支持治疗,2例给予抗癫痫治疗。随访1个月至4年,1例死亡,3例智力运动发育仍在倒退。结论 NPC是一种致死性常染色体隐性遗传病,临床表现为肝脾大、共济失调、神经退行性改变和脑干功能损害。本病目前尚无特效治疗,美格鲁特(Miglustat)早期治疗可延缓神经系统症状的出现时间、延长寿命。     

基因诊断C型尼曼-匹克病一例

患儿,男,11岁,智力减退伴运动障碍4年、反复下呼吸道感染2年.患儿自7岁开始出现智力减退、语言倒退、学习困难、感情易变、步态不稳、共济失调、震颤及吞咽困难,未予特殊治疗.上述症状进行性加重,并出现惊厥,表现为全身强直阵挛性发作.自2年前开始出现反复下呼吸道感染.既往史及家族史:患儿为一胎一产,足月顺产,出生时体检正常,母乳喂养,生后曾出现一过性黄疸,未予特殊治疗,自然消退.发病前体格发育和智力发育正常.父母非近亲婚配,家族史无特殊记载.     

基因诊断C型尼曼-匹克病一例

患儿,男,11岁,智力减退伴运动障碍4年、反复下呼吸道感染2年.患儿自7岁开始出现智力减退、语言倒退、学习困难、感情易变、步态不稳、共济失调、震颤及吞咽困难,未予特殊治疗.上述症状进行性加重,并出现惊厥,表现为全身强直阵挛性发作.自2年前开始出现反复下呼吸道感染.既往史及家族史:患儿为一胎一产,足月顺产,出生时体检正常,母乳喂养,生后曾出现一过性黄疸,未予特殊治疗,自然消退.发病前体格发育和智力发育正常.父母非近亲婚配,家族史无特殊记载.     

Isolated splenomegaly as the presenting feature of Niemann-Pick disease type C

WE DESCRIBE FOUR PATIENTS WITH NIEMANN: Pick disease type C (NPC), in whom the presentation was isolated splenic enlargement; this remained the only abnormality for a number of years. Diagnosis can be suggested by either finding abnormal storage material in a tissue biopsy specimen or by showing a modest elevation in plasma chitotriosidase activity. In patients with suggestive abnormalities, filipin staining of a skin fibroblast sample should confirm the abnormality in cholesterol trafficking. Formal esterification studies and mutation analysis should also be performed, especially if prenatal testing is to be performed in subsequent pregnancies. If the diagnosis is not considered and established, the family are at risk of having further affected children. Investigation of patients with isolated splenomegaly is not complete until NPC has been excluded.     

Growth disparity in monozygotic twins discordant for chronic renal disease

Growth data in seven pairs of monozygotic twins only one twin affected by renal disease are given. The data suggest that renal disease not only retards normal growth and sexual maturation but also affects growth potential. Therefore evaluation of the effect of renal disease and its treatment on growth should include estimation of the genetic potential for growth.     

Isolated splenomegaly as the presenting feature of Niemann-Pick disease type C.

WE DESCRIBE FOUR PATIENTS WITH NIEMANN: Pick disease type C (NPC), in whom the presentation was isolated splenic enlargement; this remained the only abnormality for a number of years. Diagnosis can be suggested by either finding abnormal storage material in a tissue biopsy specimen or by showing a modest elevation in plasma chitotriosidase activity. In patients with suggestive abnormalities, filipin staining of a skin fibroblast sample should confirm the abnormality in cholesterol trafficking. Formal esterification studies and mutation analysis should also be performed, especially if prenatal testing is to be performed in subsequent pregnancies. If the diagnosis is not considered and established, the family are at risk of having further affected children. Investigation of patients with isolated splenomegaly is not complete until NPC has been excluded.