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Endocrine, Metabolic & Immune Disorders - Drug Targets

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Case Report

A 3-Year-Old Boy with an Xp21 Deletion Syndrome: A Case Report

Author(s): Shaghayegh Sadeghmousavi, Sepideh Shahkarami, Elham Rayzan, Souran Ahmed, Farzaneh Hosseini Gharalari, Meino Rohlfs, Christoph Klein and Nima Rezaei*

Volume 22, Issue 8, 2022

Published on: 26 April, 2022

Page: [881 - 887] Pages: 7

DOI: 10.2174/1871530322666220201143656

Price: $65

Abstract

Background: Chromosome Xp21 deletion syndrome is a rare X-linked recessive defect that occurs as a result of multiple gene deletions, including Glycerol kinase (GK) and its neighboring genes, dystrophin, which causes Duchenne muscular dystrophy (DMD), and NR0B1, which causes congenital adrenal hypoplasia (CAHhttps://www.omim.org/entry/300200). Patients usually present with glycerol kinase deficiency, congenital adrenal hypoplasia, Duchenne muscular dystrophy, hyperglycerolemia, and glyceroluria, associated with DMD and/or CAH, growth failure, myopathy, osteoporosis, mental retardation, and psychomotor retardation.

Case Presentation: Herein, we report a 3-year- old boy from Iraq who had bloody diarrhea, food intolerance and abdominal cramp, adrenal insufficiency, recurrent fevers, tuberculosis (TB) infection, cervical abscess, oral thrush, cervical and mediastinal lymphadenopathies, developmental delay, and undescended testis. His parents are non-consanguine and had no family history of diseases. Next generation sequencing demonstrated a hemizygote deletion in chromosome X.

Conclusion: Loss of a large part of the X-chromosome most likely can explain the clinical findings of this patient. Contiguous gene deletion syndrome in Xp21 should be considered after diagnosing adrenal insufficiency to treat metabolic complications efficiently.

Keywords: Contiguous deletion syndromes, chromosome xp21 deletion syndrome, complex glycerol kinase deficiency, adrenal insufficiency, hypoaldosteronism, next generation sequencing.

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Graphical Abstract

[1]
Wikiera, B.; Jakubiak, A.; Zimowski, J.; Noczyńska, A.; Smigiel, R. Complex glycerol kinase deficiency - X-linked contiguous gene syndrome involving congenital adrenal hypoplasia, glycerol kinase deficiency, muscular Duchenne dystrophy and intellectual disability (IL1RAPL gene deletion). Pediatr. Endocrinol. Diabetes Metab., 2012, 18(4), 153-157.
[PMID: 23739620]
[2]
Sjarif, D.R.; Ploos van Amstel, J.K.; Duran, M.; Beemer, F.A.; Poll-The, B.T. Isolated and contiguous glycerol kinase gene disorders: A review. J. Inherit. Metab. Dis., 2000, 23(6), 529-547.
[http://dx.doi.org/10.1023/A:1005660826652] [PMID: 11032329]
[3]
Stanczak, C.M.; Chen, Z.; Zhang, Y.H.; Nelson, S.F.; McCabe, E.R. Deletion mapping in Xp21 for patients with complex glycerol kinase deficiency using SNP mapping arrays. Hum. Mutat., 2007, 28(3), 235-242.
[http://dx.doi.org/10.1002/humu.20424] [PMID: 17089405]
[4]
Dipple, K.M.; Zhang, Y.H.; Huang, B.L.; McCabe, L.L.; Dallongeville, J.; Inokuchi, T.; Kimura, M.; Marx, H.J.; Roederer, G.O.; Shih, V.; Yamaguchi, S.; Yoshida, I.; McCabe, E.R. Glycerol kinase deficiency: Evidence for complexity in a single gene disorder. Hum. Genet., 2001, 109(1), 55-62.
[http://dx.doi.org/10.1007/s004390100545] [PMID: 11479736]
[5]
McCabe, E.R.; Fennessey, P.V.; Guggenheim, M.A.; Miles, B.S.; Bullen, W.W.; Sceats, D.J.; Goodman, S.I. Human glycerol kinase deficiency with hyperglycerolemia and glyceroluria. Biochem. Biophys. Res. Commun., 1977, 78(4), 1327-1333.
[http://dx.doi.org/10.1016/0006-291X(77)91437-1] [PMID: 200232]
[6]
Guggenheim, M.A.; McCabe, E.R.; Roig, M.; Goodman, S.I.; Lum, G.M.; Bullen, W.W.; Ringel, S.P. Glycerol kinase deficiency with neuromuscular, skeletal, and adrenal abnormalities. Ann. Neurol., 1980, 7(5), 441-449.
[http://dx.doi.org/10.1002/ana.410070509] [PMID: 6249182]
[7]
Bartley, J.A.; Miller, D.K.; Hayford, J.T.; McCabe, E.R. Concordance of X-linked glycerol kinase deficiency with X-linked congenital adrenal hypoplasia. Lancet, 1982, 2(8301), 733-736.
[http://dx.doi.org/10.1016/S0140-6736(82)90921-7] [PMID: 6125810]
[8]
Renier, W.O.; Nabben, F.A.; Hustinx, T.W.; Veerkamp, J.H.; Otten, B.J.; Ter Laak, H.J.; Ter Haar, B.G.; Gabreëls, F.J. Congenital adrenal hypoplasia, progressive muscular dystrophy, and severe mental retardation, in association with glycerol kinase deficiency, in male sibs. Clin. Genet., 1983, 24(4), 243-251.
[http://dx.doi.org/10.1111/j.1399-0004.1983.tb00078.x] [PMID: 6315281]
[9]
Toyofuku, T.; Takashima, S.; Takeshita, K.; Nagafuji, H. Progressive muscular dystrophy with congenital adrenal hypoplasia: An unusual autopsy case. Brain Dev., 1986, 8(3), 285-289.
[http://dx.doi.org/10.1016/S0387-7604(86)80084-5] [PMID: 3766905]
[10]
Ginns, E.I.; Barranger, J.A.; McClean, S.W.; Sliva, C.; Young, R.; Schaefer, E.; Goodman, S.I.; McCabe, E.R. A juvenile form of glycerol kinase deficiency with episodic vomiting, acidemia, and stupor. J. Pediatr., 1984, 104(5), 736-739.
[http://dx.doi.org/10.1016/S0022-3476(84)80956-7] [PMID: 6325658]
[11]
Baranzini, S.E.; del Rey, G.; Nigro, N.; Szijan, I.; Chamoles, N.; Cresto, J.C. Patient with an Xp21 contiguous gene deletion syndrome in association with agenesis of the corpus callosum. Am. J. Med. Genet., 1997, 70(3), 216-221.
[http://dx.doi.org/10.1002/(SICI)1096-8628(19970613)70:3<216:AID-AJMG2>3.0.CO;2-U] [PMID: 9188656]
[12]
O’Driscoll, M.C.; Black, G.C.; Clayton-Smith, J.; Sherr, E.H.; Dobyns, W.B. Identification of genomic loci contributing to agenesis of the corpus callosum. Am. J. Med. Genet. A., 2010, 152A(9), 2145-2159.
[http://dx.doi.org/10.1002/ajmg.a.33558] [PMID: 20683985]
[13]
Dipple, K.M.; McCabe, E.R. Disorders of glycerol metabolism.Physician’s guide to the laboratory diagnosis of metabolic diseases; Springer, 2003, pp. 369-376.
[http://dx.doi.org/10.1007/978-3-642-55878-8_23]
[14]
Walker, A.P.; Muscatelli, F.; Monaco, A.P. Isolation of the human Xp21 glycerol kinase gene by positional cloning. Hum. Mol. Genet., 1993, 2(2), 107-114.
[http://dx.doi.org/10.1093/hmg/2.2.107] [PMID: 8499898]
[15]
Huq, A.H.; Lovell, R.S.; Ou, C-N.; Beaudet, A.L.; Craigen, W.J. X-linked glycerol kinase deficiency in the mouse leads to growth retardation, altered fat metabolism, autonomous glucocorticoid secretion and neonatal death. Hum. Mol. Genet., 1997, 6(11), 1803-1809.
[http://dx.doi.org/10.1093/hmg/6.11.1803] [PMID: 9302256]
[16]
Worton, R.G.; Thompson, M.W. Genetics of Duchenne muscular dystrophy. Annu. Rev. Genet., 1988, 22(1), 601-629.
[http://dx.doi.org/10.1146/annurev.ge.22.120188.003125] [PMID: 3071259]
[17]
Monaco, A.P.; Bertelson, C.J.; Liechti-Gallati, S.; Moser, H.; Kunkel, L.M. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics, 1988, 2(1), 90-95.
[http://dx.doi.org/10.1016/0888-7543(88)90113-9] [PMID: 3384440]
[18]
Zanaria, E.; Muscatelli, F.; Bardoni, B.; Strom, T.M.; Guioli, S.; Guo, W.; Lalli, E.; Moser, C.; Walker, A.P.; McCabe, E.R.B.; Meitinger, T.; Monaco, A.P.; Sassone-Corsi, P.; Camerino, G. An unusual member of the nuclear hormone receptor superfamily responsible for X-linked adrenal hypoplasia congenita. Nature, 1994, 372(6507), 635-641.
[http://dx.doi.org/10.1038/372635a0] [PMID: 7990953]
[19]
Zhang, J.; Liu, G.; Ruan, Y.; Wang, J.; Zhao, K.; Wan, Y.; Liu, B.; Zheng, H.; Peng, T.; Wu, W.; He, P.; Hu, F-Q.; Jian, R. Dax1 and Nanog act in parallel to stabilize mouse embryonic stem cells and induced pluripotency. Nat. Commun., 2014, 5(1), 5042.
[http://dx.doi.org/10.1038/ncomms6042] [PMID: 25284313]
[20]
Landau, Z.; Hanukoglu, A.; Sack, J.; Goldstein, N.; Weintrob, N.; Eliakim, A.; Gillis, D.; Sagi, M.; Shomrat, R.; Kosinovsky, E.B.; Anikster, Y. Clinical and genetic heterogeneity of congenital adrenal hypoplasia due to NR0B1 gene mutations. Clin. Endocrinol. (Oxf.), 2010, 72(4), 448-454.
[http://dx.doi.org/10.1111/j.1365-2265.2009.03652.x] [PMID: 19508677]
[21]
Lin, L.; Gu, W-X.; Ozisik, G.; To, W.S.; Owen, C.J.; Jameson, J.L.; Achermann, J.C. Analysis of DAX1 (NR0B1) and steroidogenic factor-1 (NR5A1) in children and adults with primary adrenal failure: Ten years’ experience. J. Clin. Endocrinol. Metab., 2006, 91(8), 3048-3054.
[http://dx.doi.org/10.1210/jc.2006-0603] [PMID: 16684822]
[22]
El-Khairi, R.; Martinez-Aguayo, A.; Ferraz-de-Souza, B.; Lin, L.; Achermann, J.C. Role of DAX-1 (NR0B1) and steroidogenic factor-1 (NR5A1) in human adrenal function.Pediatric Adrenal Diseases; Karger Publishers, 2011, Vol. 20, pp. 38-46.
[http://dx.doi.org/10.1159/000321213]
[23]
Falsaperla, R.; Romeo, G.; Sorge, A.; Bianchini, R.; DiGiorgio, A.; Trigilia, T.; Mattina, T.; Connolly, A.M. Mental retardation and early onset of weakness in a girl with a dystrophinopathy and a large Xp21-23 deletion. J. Child Neurol., 2003, 18(1), 79-81.
[http://dx.doi.org/10.1177/08830738030180012001] [PMID: 12661947]
[24]
Shaikh, M.G.; Boyes, L.; Kingston, H.; Collins, R.; Besley, G.T.; Padmakumar, B.; Ismayl, O.; Hughes, I.; Hall, C.M.; Hellerud, C.; Achermann, J.C.; Clayton, P.E. Skewed X inactivation is associated with phenotype in a female with adrenal hypoplasia congenita. J. Med. Genet., 2008, 45(9), e1-e1.
[http://dx.doi.org/10.1136/jmg.2007.055129] [PMID: 18762570]
[25]
Heide, S.; Afenjar, A.; Edery, P.; Sanlaville, D.; Keren, B.; Rouen, A.; Lavillaureix, A.; Hyon, C.; Doummar, D.; Siffroi, J-P.; Chantot-Bastaraud, S. Xp21 deletion in female patients with intellectual disability: Two new cases and a review of the literature. Eur. J. Med. Genet., 2015, 58(6-7), 341-345.
[http://dx.doi.org/10.1016/j.ejmg.2015.04.003] [PMID: 25917374]
[26]
Muscatelli, F.; Strom, T.M.; Walker, A.P.; Zanaria, E.; Récan, D.; Meindl, A.; Bardoni, B.; Guioli, S.; Zehetner, G.; Rabl, W. Mutations in the DAX-1 gene give rise to both X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Nature, 1994, 372(6507), 672-676.
[http://dx.doi.org/10.1038/372672a0] [PMID: 7990958]
[27]
Hay, I.D.; Smail, P.J.; Forsyth, C.C. Familial cytomegalic adrenocortical hypoplasia: An X-linked syndrome of pubertal failure. Arch. Dis. Child., 1981, 56(9), 715-721.
[http://dx.doi.org/10.1136/adc.56.9.715] [PMID: 7197507]
[28]
Loke, K.Y.; Larry, K.S.P.; Lee, Y.S.; Peter, M.; Drop, S.L.S. Prepubertal diagnosis of X-linked congenital adrenal hypoplasia presenting after infancy. Eur. J. Pediatr., 2000, 159(9), 671-675.
[http://dx.doi.org/10.1007/PL00008404] [PMID: 11014466]
[29]
Zachmann, M.; Illig, R.; Prader, A. Gonadotropin deficiency and cryptorchidism in three prepubertal brothers with congenital adrenal hypoplasia. J. Pediatr., 1980, 97(2), 255-257.
[http://dx.doi.org/10.1016/S0022-3476(80)80486-0] [PMID: 6105176]
[30]
Watkins, C.E.; Litchfield, J.; Song, E.; Jaishankar, G.B.; Misra, N.; Holla, N.; Duffourc, M.; Krishnaswamy, G. Chronic granulomatous disease, the McLeod phenotype and the contiguous gene deletion syndrome-a review. Clin. Mol. Allergy, 2011, 9(1), 13.
[http://dx.doi.org/10.1186/1476-7961-9-13] [PMID: 22111908]
[31]
Yamada, M.; Arai, T.; Oishi, T.; Hatano, N.; Kobayashi, I.; Kubota, M.; Suzuki, N.; Yoda, M.; Kawamura, N.; Ariga, T. Determination of the deletion breakpoints in two patients with contiguous gene syndrome encompassing CYBB gene. Eur. J. Med. Genet., 2010, 53(6), 383-388.
[http://dx.doi.org/10.1016/j.ejmg.2010.08.003] [PMID: 20813210]
[32]
Song, E.; Jaishankar, G.B.; Saleh, H.; Jithpratuck, W.; Sahni, R.; Krishnaswamy, G. Chronic granulomatous disease: A review of the infectious and inflammatory complications. Clin. Mol. Allergy, 2011, 9(1), 10.
[http://dx.doi.org/10.1186/1476-7961-9-10] [PMID: 21624140]
[33]
Rae, J.; Newburger, P.E.; Dinauer, M.C.; Noack, D.; Hopkins, P.J.; Kuruto, R.; Curnutte, J.T. X-Linked chronic granulomatous disease: Mutations in the CYBB gene encoding the gp91-phox component of respiratory-burst oxidase. Am. J. Hum. Genet., 1998, 62(6), 1320-1331.
[http://dx.doi.org/10.1086/301874] [PMID: 9585602]
[34]
Weening, R.S.; De Boer, M.; Kuijpers, T.W.; Neefjes, V.M.E.; Hack, W.W.M.; Roos, D. Point mutations in the promoter region of the CYBB gene leading to mild chronic granulomatous disease. Clin. Exp. Immunol., 2000, 122(3), 410-417.
[http://dx.doi.org/10.1046/j.1365-2249.2000.01405.x] [PMID: 11122248]
[35]
Berendes, H.; Bridges, R.A.; Good, R.A. A fatal granulomatosus of childhood: The clinical study of a new syndrome. Minn. Med., 1957, 40(5), 309-312.
[PMID: 13430573]
[36]
Finn, A.; Hadzić, N.; Morgan, G.; Strobel, S.; Levinsky, R.J. Prognosis of chronic granulomatous disease. Arch. Dis. Child., 1990, 65(9), 942-945.
[http://dx.doi.org/10.1136/adc.65.9.942] [PMID: 2221966]
[37]
Hanoglu, D.; Ozgür, T.T.; Ayvaz, D.; Köker, M.Y.; Sanal, O. Chronic granulomatous disease presenting with hypogammaglobulinemia. J. Investig. Allergol. Clin. Immunol., 2011, 21(4), 310-312.
[PMID: 21721378]
[38]
Francke, U.; Ochs, H.D.; de Martinville, B.; Giacalone, J.; Lindgren, V.; Distèche, C.; Pagon, R.A.; Hofker, M.H.; van Ommen, G-J.B.; Pearson, P.L. Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome. Am. J. Hum. Genet., 1985, 37(2), 250-267.
[PMID: 4039107]
[39]
Wilcox, D.E.; Cooke, A.; Colgan, J.; Boyd, E.; Aitken, D.A.; Sinclair, L.; Glasgow, L.; Stephenson, J.B.; Ferguson-Smith, M.A. Duchenne muscular dystrophy due to familial Xp21 deletion detectable by DNA analysis and flow cytometry. Hum. Genet., 1986, 73(2), 175-180.
[http://dx.doi.org/10.1007/BF00291610] [PMID: 3721503]
[40]
Cole, D.E.; Clarke, L.A.; Riddell, D.C.; Samson, K.A.; Seltzer, W.K.; Salisbury, S. Congenital adrenal hypoplasia, Duchenne muscular dystrophy, and glycerol kinase deficiency: Importance of laboratory investigations in delineating a contiguous gene deletion syndrome. Clin. Chem., 1994, 40(11 Pt 1), 2099-2103.
[http://dx.doi.org/10.1093/clinchem/40.11.2099] [PMID: 7955386]
[41]
Pillers, D-A.M.; Weleber, R.G.; Powell, B.R.; Hanna, C.E.; Magenis, R.E.; Buist, N.R.M. Aland Island eye disease (Forsius-Eriksson ocular albinism) and an Xp21 deletion in a patient with Duchenne muscular dystrophy, glycerol kinase deficiency, and congenital adrenal hypoplasia. Am. J. Med. Genet., 1990, 36(1), 23-28.
[http://dx.doi.org/10.1002/ajmg.1320360106] [PMID: 2159212]
[42]
Weleber, R.G.; Pillers, D-A.M.; Powell, B.R.; Hanna, C.E.; Magenis, R.E.; Buist, N.R. Aland Island eye disease (Forsius-Eriksson syndrome) associated with contiguous deletion syndrome at Xp21. Similarity to incomplete congenital stationary night blindness. Arch. Ophthalmol., 1989, 107(8), 1170-1179.
[http://dx.doi.org/10.1001/archopht.1989.01070020236032] [PMID: 2667510]
[43]
Pillers, D-A.M.; Seltzer, W.K.; Powell, B.R.; Ray, P.N.; Tremblay, F.; La Roche, G.R.; Lewis, R.A.; McCabe, E.R.B.; Eriksson, A.W.; Weleber, R.G. Negative-configuration electroretinogram in Oregon eye disease. Consistent phenotype in Xp21 deletion syndrome. Arch. Ophthalmol., 1993, 111(11), 1558-1563.
[http://dx.doi.org/10.1001/archopht.1993.01090110124037] [PMID: 8240114]
[44]
Sjarif, D.R.; Sinke, R.J.; Duran, M.; Beemer, F.A.; Kleijer, W.J.; Ploos van Amstel, J.K.; Poll-The, B.T. Clinical heterogeneity and novel mutations in the glycerol kinase gene in three families with isolated glycerol kinase deficiency. J. Med. Genet., 1998, 35(8), 650-656.
[http://dx.doi.org/10.1136/jmg.35.8.650] [PMID: 9719371]
[45]
Redman, C.M.; Russo, D.; Lee, S. Kell, Kx and the McLeod syndrome. Best Pract. Res. Clin. Haematol., 1999, 12(4), 621-635.
[http://dx.doi.org/10.1053/beha.1999.0045] [PMID: 10895256]
[46]
Peng, J.; Redman, C.M.; Wu, X.; Song, X.; Walker, R.H.; Westhoff, C.M.; Lee, S. Insights into extensive deletions around the XK locus associated with McLeod phenotype and characterization of two novel cases. Gene, 2007, 392(1-2), 142-150.
[http://dx.doi.org/10.1016/j.gene.2006.11.023] [PMID: 17300882]
[47]
Suntharalingham, J.P.; Buonocore, F.; Duncan, A.J.; Achermann, J.C. DAX-1 (NR0B1) and steroidogenic factor-1 (SF-1, NR5A1) in human disease. Best Pract. Res. Clin. Endocrinol. Metab., 2015, 29(4), 607-619.
[http://dx.doi.org/10.1016/j.beem.2015.07.004] [PMID: 26303087]
[48]
Gillard, E.F.; Chamberlain, J.S.; Murphy, E.G.; Duff, C.L.; Smith, B.; Burghes, A.H.; Thompson, M.W.; Sutherland, J.; Oss, I.; Bodrug, S.E. Molecular and phenotypic analysis of patients with deletions within the deletion-rich region of the Duchenne muscular dystrophy (DMD) gene. Am. J. Hum. Genet., 1989, 45(4), 507-520.
[PMID: 2491010]
[49]
Taglia, A.; Petillo, R.; D’Ambrosio, P.; Picillo, E.; Torella, A.; Orsini, C.; Ergoli, M.; Scutifero, M.; Passamano, L.; Palladino, A.; Nigro, G.; Politano, L. Clinical features of patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene. Acta Myol., 2015, 34(1), 9-13.
[PMID: 26155064]

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