黏多糖病II型

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黏多糖病II型

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PubMed ID
20301451 (在PubMed
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文摘

黏多糖病II型(议员II;也称为亨特综合症)的x染色体多系统障碍的特点是粘多糖(GAG)积累。绝大多数的影响个人是男性;在罕见的情况下杂合的女性明显的发现。发病的年龄、疾病严重程度和发展速度受影响的男性之间发生显著的变化。在那些早期进行性疾病,中枢神经系统的参与(清单主要由渐进认知恶化),进步的呼吸道疾病,心脏疾病通常导致死亡在第一或第二个十年的生活。在那些慢慢进步的疾病,中枢神经系统不是(或者是最小)的影响,尽管GAG积累在其他器官系统的影响可能是早期的进步程度一样的那些进步的认知能力下降。生存到成年年正常的智力是常见的缓慢进展的疾病。额外的发现在这两种形式的议员II包括:身材矮小;巨头有或没有脑积水沟通; macroglossia; hoarse voice; conductive and sensorineural hearing loss; hepato-splenomegaly; dysostosis multiplex; spinal stenosis; and carpal tunnel syndrome. Urine GAGs and skeletal survey can establish the presence of an MPS condition but are not specific to MPS II. The gold standard for diagnosis of MPS II in a male proband is deficient iduronate 2-sulfatase (I2S) enzyme activity in white cells, fibroblasts, or plasma in the presence of normal activity of at least one other sulfatase. Detection of a hemizygous pathogenic variant in IDS confirms the diagnosis in a male proband with an unusual phenotype or a phenotype that does not match the results of GAG testing. Treatment of manifestations: Interventions commonly include: developmental, occupational, and physical therapy; shunting for hydrocephalus; tonsillectomy and adenoidectomy; positive pressure ventilation (CPAP or tracheostomy); carpal tunnel release; cardiac valve replacement; inguinal hernia repair; and hip replacement. Prevention of primary manifestations: Enzyme replacement therapy (ERT) with idursulfase (Elaprase(R)), a recombinant form of human iduronate 2-sulfatase, was approved in 2006 in the United States and the European Union in individuals with the slowly progressing form of the disease. More recently studies on the outcome of ERT in children younger than age five years or individuals with early progressive pulmonary compromise or early progressive CNS disease showed that although Elaprase(R) does not cross the blood-brain barrier (and, thus, no effect on CNS disease is anticipated), early treatment may improve somatic manifestations. Treatment of boys younger than age five years was as safe and as well tolerated as for older males. Although hematopoietic stem cell transplantation (HSCT) (using umbilical cord blood or bone marrow) could provide sufficient enzyme activity to slow or stop the progression of the disease, no controlled clinical studies have been conducted in MPSII. Prevention of secondary complications: Attention to risks associated with general anesthesia. Surveillance: Depends on organ system and disease severity and usually includes annual: cardiac evaluation and echocardiogram; pulmonary evaluation including pulmonary function testing; audiogram; eye examination; developmental assessment; neurologic examination. Additional studies may include: sleep study for obstructive apnea; nerve conduction velocity (NCV) to assess for carpal tunnel syndrome; head/neck MRI to document ventricular size and cervicomedullary narrowing; and orthopedic evaluation to monitor hip disease. Evaluation of relatives at risk: While clinical experience suggests that early diagnosis of at-risk males allows initiation of ERT before the onset of irreversible changes and often before significant disease progression, it is unclear at present whether the potential benefits of early initiation of ERT justify early diagnosis by either newborn screening or testing of at-risk male relatives. MPS II is inherited in an X-linked manner. The risk to sibs depends on the genetic status of the mother. If the mother of the proband has the pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers. Germline mosaicism has been observed. Affected males pass the pathogenic variant to all of their daughters and none of their sons. Carrier testing for at-risk female relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variant in the family is known.

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