A novel mutation in the DAX1 gene in a newborn with adrenal hypoplasia congenita in Korea

Adrenal hypoplasia congenita (AHC) is a rare cause of adrenal insufficiency during neonatal period. Mutations in the gene coding for DAX1 cause X-linked adrenal hypoplasia. Most affected patients are shown to have salt wasting and hyperpigmentation on the skin during the neonatal period and require intensive medical care. In addition, it is usually associated with hypogonadotropic hypogonadism in adolescence. The DAX1 gene is expressed in the adrenal cortex, pituitary gland, hypothalamus, testis, and ovary. We report on a patient with genetically confirmed AHC whose initial clinical presentations were consistent with congenital adrenal hyperplasia. A point mutation in the DAX1 gene identified in this report resulted in a truncated DAX1 protein. Our patient was diagnosed with AHC.

Two Cases of Xp21 Contiguous Gene Deletion Syndrome

On chromosome Xp21 region, several genes such as glycerol kinase (GK) gene, adrenal hypoplasia congenita gene and Duchenne muscular dystrophy gene are located contiguously. Xp21 contiguous gene deletion syndrome involves the glycerol kinase gene deletion together with the adrenal hypoplasia congenita and/or Duchenne muscular dystrophy gene. The clinical features of a patient with a Xp21 contiguous gene deletion syndrome are sum of each disease,psychomotor retardation and lethargy for glycerol kinase deficiency, hyperpigmentation and salt wasting dehydration for congenital adrenal hypoplasia and muscular weakness and hypotonia for Duchenne muscular dystrophy. We experienced and reviewed two cases of Xp21 contiguous gene deletion syndrome with literatures.

A Case of Xp21 Contiguous Gene Deletion Syndrome with Hyperglycerolemia, Congenital Adrenal Hypoplasia and Duchenne Muscular Dystrophy

On Xp21 region several genes such as adrenal hypoplasia congenita(AHC) gene, glycerol kinase (GK) gene and Duchenne muscular dystrophy(DMD) gene are located contiguously. If there is a long deletion in that region, various combination of genetic defect can be occurred from one kind of genetic defect to all three kinds of genetic defect simultaneously. In case of more than two genetic defects simultaneously, we call it contiguous gene deletion syndrome. The major clinical manifestations of the Xp21 contiguous gene deletion syndrome are sum of each diseases, electrolyte imbalance and hyperpigmentation for adrenal hypoplasia congenita, psychomotor retardation, letharginess and convulsion for glycerol kinase deficiency and muscle weakness and hypotonia for Duchenne muscular dystrophy. Goals of the treatment are control of each disorders, glucocorticoid and mineralocorticoid for adrenal hypoplasia congenita, low fat diet and prevention of fasting and hypercatabolic status for glycerol kinase deficiency and physiotherapy for Duchenne muscular dystrophy. In case of hyponatremia and hyperkalemia combined with hyperpigmentation, adrenal hypoplasia congenita could be suspected. In glycerol kinase deficiency, markedly elevated glycerol excretion can be detected on urine organic acid analysis by gaschromatography with mass spectrometry. On Duchenne muscular dystrophy, creatinine kinase is markedly elevated on chemistry. We report here first Korean case of Xp21 contiguous gene deletion syndrome of adrenal hypoplasia congenita, glycerol kinase deficiency and Duchenne muscular dystrophy.