Our recruitment of patients continues to be excellent and represents the largest cohort of CAH and FMPP patients ever seen at one center. To date, we have enrolled over 400 patients with CAH, and 19 patients with FMPP. Comprehensive clinical phenotyping of patients with CAH due to 21-hydroxylase deficiency has been performed. Detailed clinical evaluations reveal great variation in treatment approaches of referred patients, especially amongst adults, with only 30% of patients in acceptable disease control based on adrenal hormones. Adult short stature, abnormal growth and development of children, cardiovascular risk factors, reduced bone mineral density and adrenal and testicular tumor formation are common. Further studies exploring these adverse outcomes are underway. Patients with CAH and other forms of adrenal insufficiency have been reported to have poor quality-of-life. Cognition, emotional processing, memory and quality-of-life is being evaluated. Genotyping and genetic counseling are important in the management of CAH, and genotyping has been suggested as a potential second tier screen to hormonal measurements in neonatal screening programs. The gene encoding 21-hydroxylase, CYP21A2, is mapped to the short arm of chromosome 6 (6p21.3) within the HLA complex. The high rate of genetic variability at this locus, the presence of CYP21A2 gene duplications, and the presence of the CYP21A1P pseudogene complicate the determination of disease and carrier status. An important concurrent project is the evaluation of neighboring genes, including TNXB and C4, in relation to phenotype. We described a novel CAH-Tenascin X Contiguous Gene Deletion Syndrome, termed CAH-X Syndrome. Tenascin-X deficiency, in recessive or dominant form, is a cause of hypermobility type Ehlers-Danlos Syndrome (EDS). In the first ever systematic study tenascin deficiency in CAH patients, we found that 14 (7 percent) of 193 consecutive unrelated CAH patients have the novel CAH-X Syndrome. We have subsequently identified novel chimeric genes as a cause of CAH-X, broadening the spectrum of this syndrome. Approximately 10 percent of CAH patients are now estimated to be affected by CAH-X. In addition, we showed for the first time an association at the genomic level between C4 copy number and susceptibility to psychopathology in patients with CAH. Further studies are underway to better define the clinical, molecular and biochemical aspects of CAH.
| Tella, Sri Harsha; Mallappa, Ashwini; Merke, Deborah P (2018) VISUAL VIGNETTE. Endocr Pract 24:606 |
| Miller, Walter L; Merke, Deborah P (2018) Tenascin-X, Congenital Adrenal Hyperplasia, and the CAH-X Syndrome. Horm Res Paediatr 89:352-361 |
| El-Maouche, Diala; Hargreaves, Courtney J; Sinaii, Ninet et al. (2018) Longitudinal Assessment of Illnesses, Stress Dosing, and Illness Sequelae in Patients With Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab 103:2336-2345 |
| Mallappa, Ashwini; Nella, Aikaterini A; Sinaii, Ninet et al. (2018) Long-term use of continuous subcutaneous hydrocortisone infusion therapy in patients with congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 89:399-407 |
| Hannah-Shmouni, Fady; Chen, Wuyan; Merke, Deborah P (2017) Genetics of Congenital Adrenal Hyperplasia. Endocrinol Metab Clin North Am 46:435-458 |
| Jones, Christopher M; Mallappa, Ashwini; Reisch, Nicole et al. (2017) Modified-Release and Conventional Glucocorticoids and Diurnal Androgen Excretion in Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab 102:1797-1806 |
| El-Maouche, Diala; Arlt, Wiebke; Merke, Deborah P (2017) Congenital adrenal hyperplasia. Lancet : |
| Karunasena, Nayananjani; Han, Thang S; Mallappa, Ashwini et al. (2017) Androgens correlate with increased erythropoiesis in women with congenital adrenal hyperplasia. Clin Endocrinol (Oxf) 86:19-25 |
| Mallappa, Ashwini; Nella, Aikaterini A; Kumar, Parag et al. (2017) Alterations in Hydrocortisone Pharmacokinetics in a Patient With Congenital Adrenal Hyperplasia Following Bariatric Surgery. J Endocr Soc 1:994-1001 |
| Mallappa, Ashwini; Millo, Corina M; Quezado, Martha et al. (2017) Congenital Adrenal Hyperplasia Presenting as an Adrenal Mass With Increased 18F-FDG Positron Emission Tomography Uptake. J Endocr Soc 1:1110-1112 |
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