酸性鞘磷脂酶缺乏症

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瓦瑟斯坦MP, Schuchman呃

酸性鞘磷脂酶缺乏症

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PubMed ID
20301544 (在PubMed
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文摘

临床特点:酸性鞘磷脂酶缺乏症的表现型(ASMD)沿着连续发生。患有严重的早期形式,小儿脑脊髓交感神经系统ASMD历史上被诊断出患有尼曼氏疾病类型(NPD-A)。later-onset,慢性内脏ASMD形式也称为尼曼氏疾病B型(NPD-B)。与中间表型严重程度也被称为慢性脑脊髓交感神经系统ASMD (NPD-A / B)。最常见的症状NPD-A肝脾肿大,通常被年龄三个月;随着时间的推移,肝脏和脾脏成为巨大的规模。精神运动发展过程不超过12个月的水平,之后神经恶化是无情的。未能茁壮成长通常由第二年的生活变得明显。视网膜黄斑的经典樱桃红点,这可能不会出现在头几个月,最终出现在所有受影响的孩子。引起的间质性肺疾病存储鞘磷脂的肺巨噬细胞导致呼吸道感染频繁,经常呼吸衰竭。 Most children succumb before the third year of life. NPD-B generally presents later than NPD-A, and the manifestations are less severe. NPD-B is characterized by progressive hepatosplenomegaly, gradual deterioration in liver and pulmonary function, osteopenia, and atherogenic lipid profile. No central nervous system (CNS) manifestations occur. Individuals with NPD-A/B have symptoms that are intermediate between NPD-A and NPD-B. The presentation in individuals with NPD-A/B varies greatly, although all are characterized by the presence of some CNS manifestations. Survival to adulthood can occur in individuals with NPD-B and NPD-A/B. DIAGNOSIS/TESTING: The diagnosis of ASMD is established by detection of biallelic pathogenic variants in SMPD1 and/or residual acid sphingomyelinase enzyme activity that is less than 10% of controls (in peripheral blood lymphocytes or cultured skin fibroblasts). MANAGEMENT: Treatment of manifestations: Feeding therapy and/or feeding tube as needed for nutritional support; supportive management of coagulopathy and end-stage liver disease manifestations; transfusion of blood products for life-threatening bleeding; partial splenectomy may be considered for individuals with severe hypersplenism; supplemental oxygen for symptomatic pulmonary disease; physical and occupational therapy to maximize function and to prevent contractures; early intervention and developmental support for those with developmental issues; treatment of hyperlipidemia in adults; calcium and vitamin D for osteopenia/osteoporosis; sedatives for irritability and sleep disturbance as indicated. Prevention of primary manifestations: Hematopoietic stem cell transplantation (HSCT) can correct the metabolic defect, improve blood counts, and reduce increased liver and spleen volumes but does not stabilize neurologic disease. The morbidity and mortality associated with HSCT limit its use. Prevention of secondary complications: Monitor liver function in individuals receiving hepatotoxic medications (e.g., statins for hypercholesterolemia). Surveillance: Periodic assessments of nutritional status; annual EKG; echocardiogram every two to four years; liver transaminases (ALT, AST), albumin, clotting factors, and platelet count at least annually; assess for fatigue, abdominal pain, and/or increased bleeding at least annually; radiologic measurements of liver and spleen size as needed; assess for shortness of breath at each visit; annual pulmonary function testing; chest radiograph every two to four years; assess neurologic function and frequency of headaches at least annually; monitor developmental progress, educational needs, and occupational and physical therapy needs at each visit; fasting lipid profile at least annually; assess for extremity pain at each visit; bone density assessment every two to four years; assess need for family support and resources at each visit. Agents/circumstances to avoid: Contact sports in those who have splenomegaly. GENETIC COUNSELING: All forms of ASMD (NPD-A, NPD-A/B, and NPD-B) are inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an SMPD1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Once the SMPD1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible. Biochemical prenatal diagnosis for a pregnancy at 25% risk is also possible by testing of acid sphingomyelinase enzyme activity.

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