Reductase deficiency

Jaffe ER, Hultquist DE Cytochrome reductase deficiency and enzymopenic hereditary methemoglobinemia. In The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Scriver CR et al (editors). McGraw-Hill, 2001. 

Ralph, J. Kim, H. Lu, F. Grabber, J. H. Boerjan, W. Leple, J.-C. Berrio Sierra, J. Mir Derikvand, M. Jouanin, L. Lapierre, C. Identification of the structure and origin of a thioacidolysis marker compound for ferulic acid incorporation into angiosperm lignins (and an indicator for cinnamoyl-CoA reductase deficiency). Plant J. 2008, 53, 368-379. 

Rozen, R. (1996) Molecular genetics of methylenetetrahydrofolate reductase deficiency. Journal of Inherited Metabolic Disease. 19, 589-594. 

Steroid Sa-reductase deficiency is an autosomal recessive disorder that causes decreased conversion of testosterone to dihydrotestosterone and decreased androgen action that is particularly critical during sexual development. 

The answer is D. The patient s ambiguous secondary sex characteristics and lack of menstrual activity suggest the possibility of an androgen resistance syndrome. The male karyotype and blood testosterone levels confirm this. This clinical condition might have arisen as a result of steroid 5oc-reductase deficiency or inherited defects in the androgen receptor (testicular feminization). 

A large elevation of Hey in body fluids and tissues is found in several genetic enzyme deficiencies, the homocystinurias. These include cystathionine /3-synlhase deficiency [9], the remethylation defects due to deficiency of MTHF reductase [10], methionine synthase and methionine synthase reductase deficiencies, as well as defects of intracellular cobalamin metabolism [11], namely the cblF, cblC and cblD defects. It is noteworthy that low levels of total Hey (tHcy) have been described in sulphite oxidase deficiency [12]. 

Lane AB (1985) On the nature of L-xylulose reductase deficiency in essential pentosuria. Biochem Genet 23 61-72... 

Cortisone reductase deficiency a) Cortisone reductase deficiency (CRD) b) Apparent cortisone reductase deficiency (ACRD) HSD11B1 H6PD or G6PTl(GSDlb) Iq32-q41 lpter-p36.13 1 lq23 604931,600713, 138090 602671... 

Table 5.3.6 Diagnostic urinary steroid ratios for 5a-reductase deficiency (homozygous and heterozygous), and a patient with 5 -reductase deficiency.

This condition was first noted in two markedly hirsute sisters who had elevated production of cortisol but were not Cushingoid [66]. It was found that these patients had elevated excretion of THE and related 11-oxo-steroids relative to 11/Lhydroxy-lated compounds, and so the disorder was named apparent cortisone reductase deficiency (ACRD). Subsequently, the disorder has been documented in other patients (Table 5.3.8) [3,15, 38, 54]. Presumably, the rapid and irreversible conversion of cortisol to cortisone protects against some of the negative manifestations of hypercor-tisolism. Hyperandrogenism secondary to increased cortisol clearance is the most serious clinical manifestation of the condition. 

While defective 11/1HSD I seemed the most likely cause of the disorder, no loss-of-function mutations were found in 1 IjSHSD I in the first patients investigated [61 ]. The cause of the disorder in these cases proved to be mutations in hexose-6-phos-phate dehydrogenase (H6PDH), the enzyme that supplies electrons to the NADPH utilized in oxidoreduction [15]. Later studies have found 11/311814 I mutations in some affected individuals. Thus, there are two monogenic disorders giving rise to a similar phenotype cortisone reductase deficiency caused by lljSHSD I mutations,... 

Dehydrocholesterol Reductase Deficiency, Smith-Lemli-Opitz syndrome (SLOS)... 

Fig. 5.3.6 Diagnose of Smith-Lemli-Opitz syndromesyndrome (SLOS). Urinary dehydropreg-nanetriols (DHPT 5/ -pregn-7-ene-3a,17a,20a-triol and 5j3-pregn-8-ene-3a,17a,20a-triol) partially replace PT in 7-dehydrocholesterol reductase deficiency and can be used to diagnose SLOS. The ratio of DHPT/PT correlates with dehydrocholesterol (DHC)/cholesterol (C) in affected patients (n = 34) and also correlates with clinical severity...

Biason-Lauber A, Suter SL, Shackleton CH, Zachmann M (2000) Apparent cortisone reductase deficiency a rare cause of hyperandrogenemia and hypercortisolism. Horm Res 53 260-266... 

Imperato-McGinley J, Peterson RE, Gautier T, Arthur A, Shackleton C (1985) Decreased urinary C19 and C21 steroid 5a-metabolites in parents of male pseudohermaphrodites with 5a-reductase deficiency detection of carriers. J Clin Endocrinol Metab 60 553-558... 

Imperato-McGinley J, Gautier T, Peterson RE, Shackleton C (1986) The prevalence of 5a-reductase deficiency in children with ambiguous genitalia in the Dominican Republic. J Urol 136 867-873... 

Jamieson A, Wallace AM, Andrew R, Nunez BS, Walker BR, Fraser R White PC, Connell JMC (1999) Apparent cortisone reductase deficiency a functional defect in 11 /J-hydroxysteroid dehydrogenase type 1. J Clin Endocrinol Metab 84 3570-3574... 

Malunowicz EM, Romer , Urban M, Bossowski A (2003) 11 -/3-Hydroxyslcroid dehydrogenase type 1 deficiency (Apparent Cortisone Reductase Deficiency ) in a 6-year-old boy. Horm Res 59 205-210... 

Phillipov G, Palermo M, Shackleton CH (1996) Apparent cortisone reductase deficiency a unique form of hypercortisolism. J Clin Endocrinol Metab 81 3855-3860... 

Shackleton CH, Roitman E, Kelley R (1999) Neonatal urinary steroids in Smith-Lemli-Opitz syndrome associated with 7-dehydrocholesterol reductase deficiency. Steroids 64 481-490... 

Shackleton C, Roitman E, Guo LW, Wilson WK, Porter FD (2002) Identification of 7(8) and 8(9) unsaturated adrenal steroid metabolites produced by patients with 7-dehydrosterol-A7-reductase deficiency (Smith-Lemli-Opitz syndrome). J Steroid Biochem Mol Biol 82 225-232... 

In 3-oxosteroid A4-steroid 5)3-reductase deficiency, key intermediates for cholic and chenodeoxycholic synthesis, 7a-hydroxy-4-cholesten-3-one and 7a,12a-dihy-droxy-4-cholesten-3-one undergo side-chain oxidation and conjugation to produce... 

Fig. 6.1.8a-c HPLC of the yellow-fluorescing pterins, a Standard mixture b control cerebrospinal fluid (CSF) c CSF sepiapterin reductase deficiency. HS -Hydroxyse-piapterin, S sepiapterin, X xanthopterin... 

Blau N, Bonafe L, Thony (2001) Tetrahydrobiopterin deficiencies without hyperphenyl-alaninemia diagnosis and genetics of Dopa-responsive dystonia and sepiapterin reductase deficiency. Mol Genet Metab 74 172-185... 

Milstien S, Holtzman NA, Flynn ME, Thomas GH, Butler IJ, Kaufman S (1976) Hyper-phenylalaninemia due to dihydropteridine reductase deficiency. Assay of the enzyme in fibroblasts from affected infants, heterozygotes, and in normal amniotic fluid cells. J Pediatr 89 763-766... 

Arai N, Narisawa K, Hayakawa H, Tada (1982) Hyperphenylalaninemia due to dihydropteridine reductase deficiency diagnosis by enzyme assays on dried blood spots. Pediatrics 70 426-430... 

Narisawa K, Arai N, Hayakawa H, Tada (1981) Diagnosis of dihydropteridine reductase deficiency by erythrocyte enzyme assay. Pediatrics 68 591-592... 

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