Abstract Menkes disease is a rare X-linked recessive disorder characterized by multi-systemic disorder of copper deficiency caused by ATP7A gene mutation. In this study, the clinical and laboratory features of three patients with Menkes disease were analyzed. Prenatal diagnosis had been performed for a fetus of a family. Three patients were admitted at the age of 8-9 months due to severe epilepsies and marked delayed psychomotor development. Significantly light complexion, pudgy cheeks and sparse fuzzy wooly hair were observed. On their cranial MR imaging, cortical atrophy, leukoencephalopathy, basal ganglia damage and tormesity of the intracranial vessels were found. Their plasma ceruloplasmin decreased to 70.2, 73.5 and 81 mg/L, significantly lower than normal range (210-530 mg/L). c.3914A>G (p. D1305G) was detected on ATP7A gene of case 1 and 2. A novel mutation, c.3265G>T (p.G1089X) was found in case 3. Both of them were firstly found in Chinese patients of Menkes disease. The mother of case 1 was tested at 20 weeks of pregnancy. Karyotype and ATP7A gene studies of the amniocytes were performed for the prenatal diagnosis of her fetus. Normal male karyotypes without c.3914A>G mutation on ATP7A gene was showed. Postnatal genetic analysis and normal development confirmed the prenatal diagnosis.
About author:: [1] Menkes JH, Alter M, Steigleder GK, et al. A sex-linked recessive disorder with retardation of growth, peculiar hair and focal cerebral and cerebellar degeneration[J].Pediatrics, 1962, 29 (5): 764-779.[2] Gu YH, Kodama H, Shiga K, et al. A survey of Japanese patients with Menkes disease from 1990 to 2003: incidence and early signs before typical symptomatic onset, pointing the way to earlier diagnosis[J].J Inherit Metab Dis, 2005, 28 (4): 473-478.[3] 王晓慧, 吕俊兰, 张礼萍, 等. Menkes 病三例临床及实验室 特点[J].中华儿科杂志, 2009, 47 (8): 604-606.[4] 赵程峰, 王静敏, 王菊莉, 等. Menkes 病患儿ATP7A 基因突 变及X 染色体失活分析[J].中国伤残医学, 2013, 21 (5): 37-41.[5] 麻宏伟, 陈丽英, 张海娟, 等. Menkes 病一家系二例[J].中 华医学遗传学杂志, 2001, 18 (4): 258.[6] Kaler SG. Diagnosis and therapy of Menkes syndrome, a genetic form of copper deficiency[J].Am J Clin Nutr, 1998, 67 (5): 1029- 1034.[7] Tümer Z. An Overview and update of ATP7A mutations leading to menkes disease and occipital horn syndrome[J].Hum Mutat, 2013, 34 (3): 417-429.[8] Christodoulou J, Danks DM, Sarkar B, et al. Early treatment of Menkes disease with parenteral copper-histidine: long-term follow-up of four treated patients[J].Am J Med Genet, 1998, 76 (2): 154-164.[9] Gourdon P, Liu XY, Skjorringe T, et al. Crystal structure of a copper-transporting PIB-type ATPase[J].Nature, 2011, 475 (7354): 59-64.[10] Lutsenko S, LeShane ES, Shinde U. Biochemical basis of regulation of human coppertransporting ATPases[J].Arch Biochem Biophys, 2007, 463(2): 134-148.[11] Palmgren MG, Nissen P. P-type ATPases[J].Annu Rev Biophys, 2011, 40: 243-266.[12] Horn N, Tümer Z. Menkes disease and the occipital horn syndrome[M]// Royce PM, Steinmann B. Connecitive Tissue and its Heritable Disorders: Molecular, Genetic, and Medical Aspects. 2nd ed. New York: John Wiley and Sons Inc, 2002: 651-685.[13] 黄琼辉, 王静敏, 吴晔, 等. Menkes 病临床及ATP7A 基因 突变和拷贝数改变分析[J].实用儿科临床杂志, 2012, 27 (8): 570-573.[14] 邓艳华, 王静敏, 牛争平, 等. Menkes 病患儿ATP7A 基因突 变分析[J].实用儿科临床杂志, 2007, 22 (24): 1877-1879.[15] 程晓悦, 肖江喜, 袁新宇, 等. Menkes 病的MR 影像表现[J].中华放射学杂志, 2013, 47 (7): 599-602.[16] Tümer Z, Vural B, Tunnesen T, et al. Characterization of the exon structure of the Menkes disease gene using vectorette PCR[J].Genomics, 1995, 26 (3): 437-442.[17] Tümer Z, Tunnesen T, Bohmann J, et al. First trimester prenatal diagnosis of Menkes disease by DNA analysis[J].J Med Genet, 1994, 31 (8): 615-617.[18] Horn N. Menkes' X-linked disease: prenatal diagnosis and carrier detection[J].J Inherit Metab Dis, 1983, 6(1): 59-62.[19] Heydorn K, Damsgaard E, Horn N. Accumulated experience with prenatal diagnosis of Menkes disease by neutron activation analysis of chorionic villi specimens[J].Biol Trace Elem Res, 1999, 71-72; 551-561.[20] Das S, Whitney S, Taylor J, et al. Prenatal diagnosis of Menkes disease by mutation analysis[J].J Inher Metab Dis, 1995, 18 (3): 364-365.
Cite this article:
WANG Qiao,DING Yuan,WANG Jing-Min et al. Clinical and ATP7A gene analysis of three infants with Menkes disease and prenatal diagnosis for a fetus at risk[J]. CJCP, 2014, 16(6): 624-628.
WANG Qiao,DING Yuan,WANG Jing-Min et al. Clinical and ATP7A gene analysis of three infants with Menkes disease and prenatal diagnosis for a fetus at risk[J]. CJCP, 2014, 16(6): 624-628.
Menkes JH, Alter M, Steigleder GK, et al. A sex-linked recessive disorder with retardation of growth, peculiar hair and focal cerebral and cerebellar degeneration[J].Pediatrics, 1962, 29 (5): 764-779.
[2]
Gu YH, Kodama H, Shiga K, et al. A survey of Japanese patients with Menkes disease from 1990 to 2003: incidence and early signs before typical symptomatic onset, pointing the way to earlier diagnosis[J].J Inherit Metab Dis, 2005, 28 (4): 473-478.
Kaler SG. Diagnosis and therapy of Menkes syndrome, a genetic form of copper deficiency[J].Am J Clin Nutr, 1998, 67 (5): 1029- 1034.
[7]
Tümer Z. An Overview and update of ATP7A mutations leading to menkes disease and occipital horn syndrome[J].Hum Mutat, 2013, 34 (3): 417-429.
[8]
Christodoulou J, Danks DM, Sarkar B, et al. Early treatment of Menkes disease with parenteral copper-histidine: long-term follow-up of four treated patients[J].Am J Med Genet, 1998, 76 (2): 154-164.
3.0.CO;2-T target="_blank">
[9]
Gourdon P, Liu XY, Skjorringe T, et al. Crystal structure of a copper-transporting PIB-type ATPase[J].Nature, 2011, 475 (7354): 59-64.
[10]
Lutsenko S, LeShane ES, Shinde U. Biochemical basis of regulation of human coppertransporting ATPases[J].Arch Biochem Biophys, 2007, 463(2): 134-148.
Horn N, Tümer Z. Menkes disease and the occipital horn syndrome[M]// Royce PM, Steinmann B. Connecitive Tissue and its Heritable Disorders: Molecular, Genetic, and Medical Aspects. 2nd ed. New York: John Wiley and Sons Inc, 2002: 651-685.
Tümer Z, Vural B, Tunnesen T, et al. Characterization of the exon structure of the Menkes disease gene using vectorette PCR[J].Genomics, 1995, 26 (3): 437-442.
[17]
Tümer Z, Tunnesen T, Bohmann J, et al. First trimester prenatal diagnosis of Menkes disease by DNA analysis[J].J Med Genet, 1994, 31 (8): 615-617.
[18]
Horn N. Menkes' X-linked disease: prenatal diagnosis and carrier detection[J].J Inherit Metab Dis, 1983, 6(1): 59-62.
[19]
Heydorn K, Damsgaard E, Horn N. Accumulated experience with prenatal diagnosis of Menkes disease by neutron activation analysis of chorionic villi specimens[J].Biol Trace Elem Res, 1999, 71-72; 551-561.
[20]
Das S, Whitney S, Taylor J, et al. Prenatal diagnosis of Menkes disease by mutation analysis[J].J Inher Metab Dis, 1995, 18 (3): 364-365.
