Xp21 microdeletion syndrome: Severe cause of adrenal insufficiency, muscular dystrophy, plasma lipid disorder and developmental delay in a two-month-old child with failure to thrive

Authors: F. Fencl 1;  R. Průša 2;  K. Banghová 1;  K. Bláhová 1;  Š. Vejvalková 3;  S. Koloušková 1;  J. Lebl 1
Authors‘ workplace: Pediatrická klinika UK 2. LF a FN Motol, Praha, přednosta prof. MUDr. J. Lebl, CSc., Ústav klinické biochemie a patobiochemie UK 2. LF a FN Motol, Praha , přednosta prof. MUDr. R. Průša, CSc., Ústav biologie a lékařské genetiky UK 2. LF a FN Motol, 1
Published in: Čes-slov Pediat 2012; 67 (1): 33-37.
Category: Case Report


We report a male patient presenting at the age of 2 months with failure to thrive, vomiting, dystrophy and hypotonia. The infant with unapparent family history was delivered 2 weeks post term after an uneventful pregnancy without perinatal complications. The first laboratory investigation showed severe hyponatremia (120.0 mmol/l) and hyperkalemia (7.0 mmol/l), prompting the working diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency and leading to intravenous supplementation of NaCl. However, subsequent investigations repeatedly revealed very low levels of plasma 17alpha-hydroxyprogesterone, making the 21-hydroxylase deficient form of CAH unlikely. Additionally, our patient had elevated muscle enzymes (CK 37.72 µkat/l) and myoglobin (212 µg/l), as well as hypertriglyceridemia (8.67 mmol/l) and high levels of glycerol in plasma and urine. At this point, the diagnosis of Xp21 contiguous gene deletion syndrome was considered, which is recognized as a microdeletion syndrome involving contiguous loci on the short arm of the X chromosome, including the genes DAX1 for congenital adrenal hypoplasia (AHC), DMD (Duchenne muscular dystrophy) and GK (glycerol kinase deficiency). Owing to this suspicion, ACTH test was performed with abnormal results (serum cortisol 125 mmol/l at 60th minute after application of Synacthen®), confirming the adrenal insufficiecy and leading to the initiation of therapy with mineralo- and glucocorticoids on which the ionic dysbalance improved.

Finally, a genetic study using MLPA, PCR and FISH method revealed a deletion of 8.7 Mb including DMD, DAX1, GK and IL1RAPL1 gene (associated with X-linked mental retardation). The karyotype of our patient is 46,XY,del(X)(p21.2p21.3).

The patient was on long-term substitution with gluco- and mineralocorticoids, had normal serum electrolytes and performed rehabilitation. His long-term prognosis was unfavourable due to a complete DMD gene deletion. He suddenly died probably due to a cardiac arrest within an adrenal crisis during an intercurrent infection at 3 years of age.

Key words:
microdeletion syndrome Xp21, congenital adrenal hypoplasia, Duchenne muscular dystrophy, glycerol kinase deficiency


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Neonatology Paediatrics General practitioner for children and adolescents

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