Novel Dax-1 Mutation in a Thai Boy with X-Linked Adrenal Hypoplasia Congenita (AHC): A First Report
Presentation Number: SAT-0754
Date of Presentation: June 21st, 2014
Boonchai Boonyawat*1, Nawaporn Numbenjapon1, Piriya Chantrathammachart1 and Voraluck Phatarakijnirund2
1Phramongkutklao Hospital, Bangkok, Thailand, 2Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
Background: Adrenal hypoplasia congenita (AHC) is a rare inherited disorder of adrenal development resulting in hypoplasia of adrenal gland and inability to produce glucocorticoids, mineralocorticoids and sex steroids.. The most prevalence form is an X-linked AHC caused by mutation of the DAX1 gene on chromosome Xp21. Most of X-linked AHC patients present with skin hyperpigmentation and salt losing crisis. To date, almost 200 mutations in the DAX1 have been identified but no data was available in Thailand. Here we report a case of 4-year-old Thai boy with X-linked AHC, the first case of genetically confirmed novel DAX1 mutation in Thailand.
Clinical case: A 4-year-old Thai boy presented with fever and vomiting for 3 days. He was the first child of unrelated parent. Birth history revealed an uneventful pregnancy and delivery. Birth weight was 3,200 gm. The past medical history was unremarkable except his skin progressively more pigmented since early infancy. Physical examination revealed normal vital signs, no dysmorphic feature with normal genital development and addisonian hyperpigmentation which prominent at skin crease, gum and knuckles. Laboratory investigations showed hyponatremia (Na 128 mmol/L), hyperkalemia (K 5.2 mmol/L), and hypochloremia (Cl 94 mmol/L). Hormonal evaluation revealed low baseline cortisol level (0.89 mg/dL) which is not rising after 250 mg ACTH stimulation test. ACTH level was very high (13,270 pg/mL) as well as plasma renin activity (470 ng/dl/hr). Aldosterone and 17-hydroxyprogesterone levels were normal. The karyotype was 46,XY. A diagnosis of X-linked AHC was established. Glucocorticoid and mineralocorticoid replacement therapy were initiated.
Mutation analysis by direct DNA sequencing of all 2 coding exons and exon-intron junction of the DAX1 gene revealed a novel hemizygous GG deletion (c.1148_1149delGG; codon 383). This frameshift mutation resulted in a premature termination codon at the position 387 and was predicted to encode a truncated DAX1 protein missing a portion of ligand binding domain. Molecular analysis from all other family members revealed only a heterozygous for the same mutation in the mother, indicating that the mutation found in the index case was inherited from his carrier mother.
Conclusion: We report a case of X-linked adrenal hypoplasia congenita with established a novel hemizygous frameshift mutation in the DAX1 gene. Mutation analysis is important not only for diagnostic confirmation in the index case but also for carrier detection in his mother which provided a proper management and appropriate genetic counseling for this family.
Nothing to Disclose: BB, NN, PC, VP