In CAH due to 21-OH deficiency, phenotype-genotype correlation is known. However, the same genetic events may cause different clinical forms of the disease. A case of CAH associated with the P30L in the CYP21A2 gene in presented. The Caucasian girl was born normally and growing healthy till the age of 3.y., when her mother noticed pubic hair growth; at the age of 4 she had acne and an increasing sweating. At 6 y. of age, she was brought to paediatric endocrinologist for the first time due to adrenarche progression and accelerated growth. At examination, her height was +2.5 SDS with no weight excess, when MPH was Median. Her BA was 5 y. accelerated and counted 11y., with poor final adult height prognosis, i.e. 140 cm (−4SDS). Blood biochemistry found moderately elevated 17-OP and normal cortisol. The child was diagnosed with CAH, most probably non-classical, and treatment with 12 mg/m2/day of hydrocortisone divided in 3 doses was prescribed. The karyotype was 46,XX. At 6.5 y., breast development started with continuing growth acceleration and some BA progression. Pelvic US found pubertal uterine size. The test with GnRH-agonist confirmed central precocious puberty in the child. A low serum sodium with elevated potassium levels were found at the next biochemical exam. Simultaneously, treatment with GnRH-agonist 3.75 mg once in 28 days, and fludrocortisone 50100 μg daily was prescribed. The patient was under this combined therapy for 3.5 y. Neither salt loosing no further puberty progression was seen. At the age of 10 y., GnRH-agonist was withdrawn. When molecular diagnosis became available, the homozygous mutation P30L in the CYP21A2 gene was discovered. The patient is currently 11 y.o., under GC and MC replacement, her BA is 12 y., with final height prognosis of 160 cm. As it is known, the P30L mutation is mostly associated with NC CAH. The clinical course in our patient is more in favor for SV CAH and confirmes again that genotype-phenotype correlation in CAH is not always absolute. Combination of the replacement GC therapy with MC and experimental GnRH-analogues may improve auxological outcome of the patient and provide better quality-of-life in the future.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology