Clinical, Biochemical and Genetic profile of Patients with Congenital Adrenal Hyperplasia due to 11-βHydroxlase deficiency.

Clinical, Biochemical and Genetic profile of Patients with Congenital Adrenal Hyperplasia due to 11-βHydroxlase deficiency**.**

Introduction

Congenital adrenal hyperplasia (CAH) is a Mendelian disorder transmitted as an autosomal recessive trait. The most prevalent form of CAH arises from steroid 21-hydroxylase enzyme deficiency, accounting for ∼90–95% of all cases (1, 2). In contrast, CAH caused by steroid 11β-hydroxylase deficiency is considerably rare, with a prevalence of 5–8% (3), from which we estimate an overall frequency of 1 in 100,000 live births. Two homologous enzymes, 11β-hydroxylase and aldosterone synthase,areencodedbythe CYP11B1 and CYP11B2 genes,respectively on chromosome 8(3, 4). The two encodedhomologs,however, havedistinctfunctionsincortisolandaldosterone synthesis, respectively (3). In the zona fasciculata, CYP11B1converts 11-deoxycortisol and 11-deoxycorticosterone to cortisol and corticosterone, respectively, and is regulated by adrenocorticotropic hormone secreted by the pituitary. In contrast, in the zona glomerulosa CYP11B2converts corticosterone to aldosterone with the intermediate production of 18-hydroxycorticosterone. These latter conversions are controlled mainly by the renin angiotensin system and serum potassium concentration (3).

Mutations in the CYP11B1 gene results in decreased conversion of 11-deoxycortisol and DOC to cortisol andcorticosterone, respectively in zona fasciculata (5).The low cortisol level activates the negative feedback mechanism of pituitary-adrenal axis leading to increased ACTH production with consequential adrenal cortex hyperplasia.

The increased steroid precursors are then shunted into the androgen pathway. Elevated mineralocorticoid precursors and androgens including androstenedione and testosterone lead to development of hyporeninemic hypertension and symptoms of hyperandrogenism, respectively (6). This leads to virilisation in female fetus, and males present with isosexual precocity, with or without hypertension.

11-beta hydroxylase deficiency being a rare disorder there are a very few studies on patients with 11-β-hydroxylase deficiency CAH in Indian population.

Thus, we intend to study clinical profile and geneticsof this disorder which may provide a useful tool for genetic counselling and to formulate a treatment plan for better management of these patients.

Aims and objectives

·        To study the clinical and biochemical profile of genetically diagnosed cases of congenital adrenal hyperplasia (CAH) due to 11-βHydroxylase deficiency.

Type of study: Retrospective study

**Sample size:**All patients who have attended the endocrine OPDat leastonce since the year 2000 will be included in the study (approximately 20 patients).

Inclusion criteria

·        Patients with Congenital adrenal hyperplasia due to 11-βhydroxylase deficiency.

Exclusion criteria:

·        Patients with clinical characteristics of 11-β hydroxylase deficiency withoutconfirmed genetic diagnosis.

·        Inadequate Biochemical data.

Methodology:

This is a retrospective study conducted at a tertiary health care center. Data will be collected (both baseline and follow up) from medical record of patients all genetically diagnosed cases of 11-β Hydroxylase deficiency .All the clinical features (age of presentation, age of diagnosis, gender, family history, symptoms,examination findings), biochemical characteristics (17-OHP, 11 Deoxycortisol, Plasma Renin activity/direct renin concentration , Sodium , Potassium etc) will be recorded. Genetic analysis is offered to patients with CAH at department of endocrinology K.E.M as a standard of care. Some patients have borne the cost of genetic analysis, while some have been offered help through donations or trust funds. The genetic testing from K.E.M is usually out sourced to Medgenome Laboratories.