21-hydroxylase, deficiency

Alaniz, R.C. et al., Dopamine P-hydroxylase deficiency impairs cellular immunity, Proc. Natl. Acad. Sci. USA, 96, 2274, 1999. 

Vitamin D deficiency may also occur through inadequate dietary intake, gut (poor absorption), renal disease (1-hydroxylase deficiency or failure to reclaim calcium from the glomerular filtrate), or liver disease (25-hydroxylase deficiency). The slightly low haemoglobin concentration and pale stained (hypochromic) red cells suggested a coincident mild iron deficiency. 

Phenylalanine hydroxylase deficiency, giving rise to phenylketonuria (PKU) (Box 3.9). 

Congenital enzymatic defects in the adrenal biosynthetic pathways lead to diminished cortisol and aldosterone production and release. In these conditions, corticotrophin secretion is increased, and adrenal hyperplasia occurs, accompanied by enhanced secretion of steroid intermediates, especially adrenal androgens. More than 90% of cases of congenital adrenal hyperplasia are due to 21-hydroxylase deficiency, which is cre-afed by mufafions in fhe CYP21 gene encoding fhe en-... 

Serum steroid hormonal profiles by reversed-phased liquid chromatography in patients with 17a-hydroxylase deficiency. (158)... 

In patients suspected of congenital adrenal hyperplasia, to identify 21-hydroxylase deficiency, 11- hydroxylase deficiency, and 3l3-hydroxy-A5 steroid dehydrogenase deficiency, based on the steroids that accumulate in response to ACTH administration (see Figure 39-1 and Chapter 39)... 

Merke DP et al Future directions in the study and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Ann Intern Med 2002 136 320. [PMID 11848730]... 

Patients with Refsum disease may have extremely high phytanic acid levels, up to 1500 pmol/1, whereas pristanic acid is low (< 1 pmol/1) as a consequence of the phytanoyl-CoA hydroxylase deficiency. Less pronounced phytanic acid elevations will be observed in RCDP type 1 patients, which applies to both the classical form as well as the variant forms. Values may range from 200 to 900 pmol/1, somewhat depending on age. There is some discussion on the time of onset of phytanic acid accumulation in the classical neonatal RCDP-patients. Normal plasma phytanic acid levels (0.7-5.8 pmol/1) were recorded in the authors laboratory in patients aged less than 1 week. Two- to three-week-old RCDP patients had increased phytanic acid levels of 9.1 -13.2 pmol/1. Classical patients invariably had undetectable plasmalogen levels of the erythrocytes at any age. 

I consider hormonal steroid profiles to be those analyses that encompass a panel of steroids that can diagnose different endocrine abnormalities. A panel of multiple steroids used to diagnose a single condition, for example 21-hydroxylase deficiency, would not be a steroid profile under this definition. 

HD 21 -Hydroxylase deficiency 5PT 5-pregnene-3/ ,17a,20a-triol, 160HDHEA 16a-hydroxyDHEA, 17HP 17a-hydroxy-pregnanolone, d days, Fs cortisol metabolites, m months, yrs years, Pat patient, PTONE pregnanetriolone... 

P450 ORD, "Combined 17- and 21 -Hydroxylase Deficiency" and the Antley-Bixler Syndrome... 

Reports on serum steroids in affected patients (not analyzed by LC-MS) show elevated 17-OHP and low testosterone concentrations. In order to prevent confusion of this condition with 21- or 17-hydroxylase deficiency, the following panel of steroids should be analyzed 17-OHP, 21-deoxycortisol, corticosterone, progesterone, and pregnenolone all of which should be elevated. Cortisol should be normal and testosterone and DHEA (including sulfate) low for age. Patients show a blunted cortisol response to ACTH stimulation. 

Patients with 11/1-hydroxylase deficiency present with features of androgen excess, including masculinization of female newborns and precocious puberty in male children. There are two human isozymes that are responsible for cortisol and aldosterone synthesis, respectively. The CYP11B1 enzyme (p45011B) converts DOC to corticosterone (B) and 11-deoxycortisol (S or 11-dihydrocortisol) to cortisol (F). It is also capable of 18-hydroxylating DOC but cannot convert to aldosterone. The latter transformation is carried out by CYP11B2 (also known as aldosterone synthase), which encompasses activity for 18-hydroxylation and subsequent 18-oxidation. When CAH is associated with hypertension, deficient lljS-hydroxylase (CYP11B1) is suspected at this time more than ten mutations have been defined in affected individuals [103]. 

Only 21-hydroxylase deficiency is routinely diagnosed prenatally, and then only in patients considered at risk for the condition. Although elevated levels of 17-OHP are found in amniotic fluid, molecular techniques are generally used for diagnosis. 

Honour JW, Tourniaire J, Biglieri EG, Shackleton CHL (1978) Urinary steroid excretion in 17a-hydroxylase deficiency. J Steroid Biochem 9 495-505... 

Joannou GE (1981) Identification of 15/5-hydroxylated C21 Steroids in the neo-natal period the role of 3a,15/),17a-trihydroxy-5/ -pregnan-20-one in the perinatal diagnosis of congenital adrenal hyperplasia (CAH) due to a 21-hydroxylase deficiency. J Steroid Biochem 14 901-912... 

White PC (2001) Steroid 11/J-hydroxylase deficiency and related disorders. Endocrinol Metab Clin North Am 30 61-79... 

The initial steps in BA synthesis are characterised by the introduction of a hy-droxylic group in the la position, or in position 27, followed by another in the la position into the cholesterol nucleus. Both synthetic pathways (the neutral and the acidic pathways) possess a distinct microsomal 7-oxysterol hydroxylase, which is regulated by different genes. The most recently described disorder of BA synthesis is cholesterol 7a-hydroxylase deficiency, in which their decreased production through the classical pathway is partially balanced by activation of the alternative pathway. Cholesterol levels increase in the liver, with a consequent low-density lipoprotein hypercholesterolemia, and cholesterol gallstones may result, although there is no liver disease. In contrast, a defect in the conversion of 27-hydroxy-cholesterol to la,27-dihydroxy-cholesterol due to deficiency of the oxysterol 7a-hydroxylase specific for the alternate pathway, causes severe neonatal liver disease [8]. 

Inspection of Table 6.2.2 shows that for tyrosine hydroxylase deficiency, only the concentration of HVA is decreased [2]. However, in cases of AADC deficiency, in... 

To date, a fully documented case of tryptophan hydroxylase deficiency has not been described. However, such a deficiency would be predicted to have a characteristic CSF profile (i.e. an isolated decrease in CSF 5HIAA concentration). 

Brautigam C, Wevers RA, Jansen RJT, Smeitink JAM, et al (1998) Biochemical hallmarks of tyrosine hydroxylase deficiency. Clin Chem 44 1897-1904... 

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