NEUROCHEMISTRY OF MUCOPOLYSACCHARIDOSES - BRAIN LIPIDS AND LYSOSOMAL ENZYMES IN PATIENTS WITH 4 TYPES OF MUCOPOLYSACCHARIDOSIS AND IN NORMAL CONTROLS
NEUROCHEMISTRY OF MUCOPOLYSACCHARIDOSES - BRAIN LIPIDS AND LYSOSOMAL ENZYMES IN PATIENTS WITH 4 TYPES OF MUCOPOLYSACCHARIDOSIS AND IN NORMAL CONTROLS
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DOI：
10.1111/j.1471-4159.1978.tb12388.x
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发表时间：
1978-01-01
影响因子：
4.7
通讯作者：
DEKABAN, AS
中科院分区：
文献类型：
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作者：
CONSTANTOPOULOS, G;DEKABAN, AS
在未受影响的对照组和 6 名粘多糖贮积症 (MPS) 患者的大脑灰质和白质以及肝脏中测量了脂质和某些溶酶体酶。其中 3 名患者患有 I 型 MPS (Hurler)、1 名 II 型 (Hunter)、1 名 IIIA 型 (Sanfilippo A) 和 1 名 V 型 (Scheie)。这些组织的糖胺聚糖（GAG）先前已得到充分表征。除 MPS V 型患者外，所有患者的灰质中正常情况下较小的单唾液酸神经节苷脂 GM2 和 GM3 在白质中显着增加，白质中的含量较小。在所有 MPS I、II 和 IIIA 患者中，平均 GM2 占灰质和白质总神经节苷脂神经氨酸的 8.2% 和 6.3%，GM3 分别占 11.8% 和 6.0%（正常受试者有小于 1)。 MPS I、MPS II 和 MPS IIIA 患者的灰质中的神经酰胺二己糖苷也有所增加。鞘脂异常仅在含有过量部分降解的皮肤素和硫酸肝素或单独的硫酸肝素的组织中发现。在所测定的6种酸性水解酶中，β-氨基葡萄糖苷酶的活性在脑和肝脏中均增加，而α-半乳糖苷酶和β-半乳糖苷酶的活性降低，特别是在肝脏中。 MPS患者组织中积累的部分降解的硫酸肝素（可能还有硫酸皮肤素）可能会抑制各种鞘脂的分解代谢酶。反过来，鞘脂的积累至少可能是 MPS I、II 和 IIIA 患者大脑损伤和智力迟钝的部分原因。
Lipids and certain lysosomal enzymes were measured in the cerebral gray and white matter and in the liver of unaffected controls and 6 patients with mucopolysaccharidosis (MPS). Three of the patients had MPS Type I (Hurler), 1 Type II (Hunter), 1 Type IIIA (Sanfilippo A) and 1 Type V (Scheie). The glycosaminoglycans (GAG) of those tissues have been fully characterized previously. The normally minor brain monosialogangliosides GM2 and GM3 were markedly increased in the gray and to a lesser extent in the white matter of all the patients, except the patient with MPS Type V. On an average GM2 comprised 8.2 and 6.3 and GM3 11.8 and 6.0% of the total ganglioside neuraminic acid of the gray and white matter, respectively, in all patients with MPS I, II and IIIA (normal subjects had less than 1). Ceramide dihexoside was also increased in the gray matter of the patients with MPS I, MPS II and MPS IIIA. The sphingolipid abnormalities were found only in tissues containing excessive amounts of partially degraded dermatan and heparin sulfates or heparin sulfate alone. Of the 6 acid hydrolases assayed, the activity of .beta.-glucosaminidase was increased in both brain and liver, while that of .alpha.-galactosidase and .beta.-galactosidase was diminished, particularly in the liver. The partially degraded heparin sulfate (and perhaps the dermatan sulfate) which accumulate in the tissues of the patients with MPS may inhibit catabolic enzymes of various sphingolipids. In turn, accumulation of sphingolipids could be responsible at least for some of the brain damage and the mental retardation in MPS I, II and IIIA.