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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 place of work: 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 the journal: Čes-slov Pediat 2012; 67 (1): 33-37.
Category: Case Report

Summary

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


Zdroje

1. Sjarif DR, Ploos van Amstel JK, Duran M, Beemer FA, Poll-The BT. Isolated and contiguous glycerol kinase gene disorders: a review. J Inherit Metab Dis 2000; 23(6): 529–547.

2. Stanczak CM, Chen Z, Zhang YH, Nelson SF, McCabe ER. Deletion mapping in Xp21 for patients with complex glycerol kinase deficiency using SNP mapping arrays. Hum Mutat 2007; 28(3): 235–242.

3. Skinningsrud B, Husebye ES, Gilfillan GD, Frengen E, Erichsen A, Gervin K, et al. X-linked congenital adrenal hypoplasia with hypogonadotropic hypogonadism caused by an inversion disrupting a conserved noncoding element upstream of the NR0B1 (DAX1) gene. J Clin Endocrinol Metab 2009; 94(10): 4086–4093.

4. Wheeler B, George PM, Mackenzie K, Hunt P, Potter HC, Florkowski CM. Three cases of congenital adrenal hypoplasia with novel mutations in the (NROB1) DAX-1 gene. Ann Clin Biochem 2008; 45(Pt 6): 606–609.

5. Lebl J, Jufieda K, Kalvachová B, Votava F. Chlapec s adrenální insuficiencí a defektem DAX-1 genu. Diabetologie, Metabolismus, Endokrinologie, Výživa 2001; 2: 136–139.

6. Seemanová E, Hedvičáková P. Duchennova muskulární dystrofie u dívky. Čes-slov Pediat 2007; 4:234–238.

7. Lewis B, Harbord M, Keenan R, Carey W, Harrison R, Robertson E. Isolated glycerol kinase deficiency in a neonate. J Child Neurol 1994; 9(1): 70–73.

8. Darras BT, Francke U. Myopathy in complex glycerol kinase deficiency patients is due to 3’ deletions of the dystrophin gene. Am J Hum Genet 1988; 43(2): 126–130.

9. Seltzer WK, Angelini C, Dhariwal G, Ringel SP, McCabe ER. Muscle glycerol kinase in Duchenne dystrophy and glycerol kinase deficiency. Muscle Nerve 1989; 12(4): 307–313.

10. Ozer EA, Kaya A, Yildirimer M, Guler O, Can S, Aydinlioglu H. A novel DAX1 gene mutation in a Turkish infant with X-linked adrenal hypoplasia congenita. Eur J Pediatr 2009; 168(3): 367–369.

11. Yang F, Hanaki K, Kinoshita T, Kawashima Y, Nagaishi J, Kanzaki S. Late-onset adrenal hypoplasia congenita caused by a novel mutation of the DAX-1 gene. Eur J Pediatr 2009; 168(3): 329–331.

Štítky
Neonatology Paediatrics General practitioner for children and adolescents

Článok vyšiel v časopise

Czech-Slovak Pediatrics

Číslo 1

2012 Číslo 1
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