17 alpha-hydroxylase deficiency overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
Overview
17 alpha-hydroxylase deficiency was first reported by Dr. Edward G. Biglieri, an American endocrinologist, in 1963-1966 following publication of a case report. 17 alpha-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene CYP17A1, which encodes for the enzyme 17 alpha-hydroxylase and 17,20-lyase. 17 alpha-hydroxylase deficiency is transmitted in an autosomal recessive pattern. Mineralocorticoid excess and lack of androgens are two main features in this disease. Mutations in the CYP17A1 gene cause 17 alpha-hydroxylase deficiency. This gene is located on chromosome 10. 17 alpha-hydroxylase deficiency is a rare disease and since 2010, only 130 individuals with severe, confirmed disease had been documented. Worldwide incidence of 17 alpha-hydroxylase deficiency is low, especially compared with other forms of CAH. New cases of 17-hydroxylase deficiency continue to be reported. The most potent risk factor in the development of 17 alpha-hydroxylase deficiency is the presence of family history of 17 alpha-hydroxylase. Symptoms of 17 alpha-hydroxylase deficiency include delayed puberty and primary amenorrhea. Patients with 17 alpha-hydroxylase deficiency usually appear normal. Physical examination of patients with 17 alpha-hydroxylase deficiency is usually remarkable for gynaecomastia, hypertension, and sexual infantilism. Laboratory findings consistent with the diagnosis of 17 alpha-hydroxylase deficiency include increased deoxycorticosterone and corticosterone with low cortisol. The mainstay of therapy for 17 alpha-hydroxylase deficiency is glucocorticoid therapy. Spironolactone and estrogen also may be used. Affected 46,XY patients require gonadectomy to prevent malignant degeneration of testes. The reconstruction surgery for ambiguous genitalia in genetically male patients may be considered.
Historical Perspective
17 alpha-hydroxylase deficiency was first reported by Dr. Edward G. Biglieri, an American endocrinologist, in 1963-1966 following publication of a case report.
Classification
17 alpha-hydroxylase deficiency may be classified into two types, based on severity and clinical findings: partial and severe form.
Pathophysiology
17 alpha-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene CYP17A1, which encodes for the enzyme 17 alpha-hydroxylase and 17,20-lyase. 17 alpha-hydroxylase deficiency is transmitted in an autosomal recessive pattern. Mineralocorticoid excess and lack of androgens are two main features in this disease.
Causes
Mutations in the CYP17A1 gene cause 17 alpha-hydroxylase deficiency. This gene is located on chromosome 10.
Differential Diagnosis
17 alpha-hydroxylase deficiency must be differentiated from diseases that present with primary amenorrhea and female external genitalia such as pregnancy, androgen insensitivity syndrome, 3beta-hydroxysteroid dehydrogenase type 2 deficiency, gonadal dysgenesis, testicular regression syndrome, LH receptor defects, 5-alpha-reductase type 2 deficiency, mullerian agenesis, primary ovarian insufficiency, hypogonadotropic hypogonadism and turner syndrome.
Epidemiology and Demographics
17 alpha-hydroxylase deficiency is a rare disease and since 2010, only 130 individuals with severe, confirmed disease had been documented. Worldwide incidence of 17 alpha-hydroxylase deficiency is low, especially compared with other forms of CAH. New cases of 17-hydroxylase deficiency continue to be reported.
Risk Factors
The most potent risk factor in the development of 17 alpha-hydroxylase deficiency is the presence of family history of 17 alpha-hydroxylase.
Screening
There is insufficient evidence to recommend routine screening for 17 alpha-hydroxylase deficiency.
Natural history, Complications and Prognosis
If left untreated, patients with 17 alpha-hydroxylase deficiency may progress to develop malignant hypertension. Common complications of 17 alpha-hydroxylase deficiency include muscle weakness, metabolic alkalosis, and infertility. Prognosis is generally good with treatment.
History and Symptoms
Symptoms of 17 alpha-hydroxylase deficiency include delayed puberty and primary amenorrhea.
Physical Examination
Patients with 17 alpha-hydroxylase deficiency usually appear normal. Physical examination of patients with 17 alpha-hydroxylase deficiency is usually remarkable for gynaecomastia, hypertension, and sexual infantilism.
Laboratory Findings
Laboratory findings consistent with the diagnosis of 17 alpha-hydroxylase deficiency include increased deoxycorticosterone and corticosterone with low cortisol.
CT
Abdominal CT scan findings consistent with 17 alpha-hydroxylase deficiency includes bilateral symmetric enlargement of the adrenal glands.
MRI
Abdominal MRI findings consistent with 17 alpha-hydroxylase deficiency includes bilateral symmetric enlargement of the adrenal glands.
Echocardiography or Ultrasound
On ultrasound, 17 alpha-hydroxylase deficiency is characterized by enlarged, wrinkled, and cerebriform adrenal glands.
Other Imaging Findings
There are no other imaging studies available for the diagnosis of 17 alpha-hydroxylase deficiency.
Other Diagnostic Studies
Prenatal diagnosis may be used in the diagnosis of 17 alpha-hydroxylase deficiency. Different tests may be used such as amniotic fluid sampling and oligonucleotide hybridization of deoxyribonucleic acid (DNA) obtained from chorionic villus biopsies; and utilize fetal DNA extracted from maternal blood through noninvasive methods.
Medical Therapy
The mainstay of therapy for 17 alpha-hydroxylase deficiency is glucocorticoid therapy. Spironolactone and estrogen also may be used.
Surgery
Affected 46, XY patients require gonadectomy to prevent malignant degeneration of testes. Reconstructive surgery for ambiguous genitalia in genetically male patients may be advised.
Prevention
Prenatal diagnosis of 17 alpha-hydroxylase deficiency is advised in order to prevent complications of the disease further in life. Prenatal administration of dexamethasone, which is the drug of choice helps prevent complications.