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
Abstract
We report amale patient presenting at the age of 2months 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 (serumcortisol 125mmol/l at 60thminute after application of Synacthen(R)), 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). 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.