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Steroid Sulfatase Deficiency

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Steroid Sulfatase Deficiency Pediat. Res. 11: 89.i-897 ( I 977) Amniotic tluid steroid sulfatase placenta steroid sulfatase deficiency Steroid Sulfatase Deficiency LARRY J. SHAPIRO."''' LARRY COUSlc\S, ARVAc\ L. FLUHARTY. RICHARD L. STEVE:\S, AND IIAYATO KIIIARA /)i1·isio11 of.\frdical G,·11t·tics. !)<'f'<1Tt111c11t of l'cdiatrin·. and the llt-['t1Tt111c11t ofOh.11,·trin· and G_r11ccologr. I/arbor Gc11ern/ 1/wpital C11111['11.,. UCLA School of .\fnlici11e. 1111d the UCLA-.\'c11m['.1ychiatric l11.1ti1111c-l'a.-ijic State 1/mpital Un,·ardt Groll['. 1'0111m111 . California. USA Summar)· additional picn:s of information about this disonkr. First. this cnzynwpathy docs not afkct thc activities of lysosomal sulfatasc Placental steroid sulfatase delicienc)· is a genetic disorder onl)· and so thcsc paticnts should not hi: cxpcctl·d to dcvdop a recent!)· reported in the medical literature. '.\lost documented sulfolipid or mucopolysaccharidc storagc discasc in latcr lifc . cases of placental sulfatase deficienc) ha,·e been marked b)· Sccond. this inborn dckct is not localitl·d to thc placcnta. hut is dcla) in onset of labor, lack of cenical dilatation, and relath·e gcncralizcd to othcr somatil- tissucs (at kast to n1lturcd fibro­ refractoriness of OX)tocic agents and amniotom,·, \Ve ha,·e stud­ blasts) anJ so may havc l'linical conscqucnccs not pn:viously ied the placenta, cultured fibroblasts, and amniotic fluid l"ells apprl·ciatcd. from an afTected patient. The acthities of estrone sulfatasc, pregnenolone sulfatase, deh)droepiandrosterone sulfatase, and ar) lsulfatase C in the plal·enta from the 1>atient were snerel)· CASE REPORT deficient. Ar)lsulfatases ,\ and B were present at le\'Cls within FF, the prohand's mothcr. a 19-yl·ar-old gravid a 2. para I the normal range for this tissue. Caucasian kmak had hcr first prcgnancy tcrminatcd by Fibroblast deh)droepiandrosterone sulfatase acthit) ,ir­ was ccsarcan scction at 42 wccks of gestation bccausc of ktal dis­ tuall)· absent in the patient's cells and present at normal le,·els in trcss. After spontancous rupturc of thc mcmbrancs, oxytocin indh·iduals with a ,·ariet)· of l)sosomal disorders. It would thus stimulation of labor was attcmptcd in spite of an undkctcd. appear that the mutation responsible for steroid sulfatase tll·li­ undilatcd cervix. Thi: proccdurc was stoppcd whcn kt al brady­ cienc) is geneticall) and hiochemicall) · distinct from those in­ cardia dcvclopcd. At thc timc of ccsarcan scction. a truc knot in ,ol\'Cd in the l)sosomal sulfatase delicienc) states. The cell thc cord was found. Thi: mak infant has dcvdopcd normally culture studies further Slll,!l,!l'St that the defect is a generalill•d dcspitc a I min Apgar scorc of I . one which should he detectable in midtrimester of pregnanc)· TFs past mcdical history. family history. and sccond prl·g­ and ma)· ha,·e phenot)pic l·onse<1uences in later postnatal life. nancy wcrc uncomplicated. Shi: was rderrcd to thc Spccial Oh­ stctric Clinic at I !arbor Gcncral Hospital at 35 \n·cks of gesta­ Speculation tion hccausc of hcr prcvious ccsarean scction and qucstionahk hyp.,thyr.,idism. Thyroid furn:tion slllllics wcrc normal. but Furtla·r clinical and;,, l"itro studies of patients with this rare scrum cstriol was undetcctahlc. Fctal hcart toncs. fundal inborn error of metabolism should ) icld information regarding crowth. and ktal activity wcrc normal. Gray seal.: ultrasonoc­ the role of steroid sulfatase in normal metabolism, and in the raphy rcvcakd a norm:tl biparictal diamct-cr l'\lllsistcnt with progress of normal parturition. Once the mechanism h)' which ccstational acc. Prodromal labor bccan at 39 wccks of ccsta­ the leHI of acth·it)· of this elll) me exerts an efTect upon labor tion. and aft;r mature fetal surfactar;t kvds wcrc l'Onfirn;l·d. a and delher,· is known, appropriate pharmacologic in\'Cn·ention rcpcat lowcr utcrinc scgmcnt ccsarcan scction was pcrformcd . might prmide a means for the inhibition of premature labor. Thi: 3 .2<,0-g mak ncwborn had Apgar scorcs of 7 at I min and (J at 5 min. The placcnta wcighl·d 475 g and was grossly and histo­ lo!!icallv normal. Thi: infant's nurscrv coursc was unrcmarkahk . Thi: lk·tnmination of matl'rnal urinary cstriol l' Xnction is a Pl;ysic;;I anJ ncurologic c:-.amin.11io-ns wcrc normal cx,·cpt for frcqucntly utilizcd mcthod for monitoring thc status of high risk first dcgrcc hypospadius. Cord cortisol was 17 .0 µ.g/ I()() ml pregnancies (3). Sinl·c thc production of the largc amounts of and scrum ckctrolytcs werc normal. Thne was no evidence of cstriol observcd during gcstation is lkpcndcnt on thc intcgrity of kthargy. \'omiting. or diarrhl·a and thc infant has don.: \\di the ktal-placrntal-matcrnal unit. implications for thc wdl bcing sin cc birth. of a prl·gnancy may hi: rdkctcd in altcrations of this paraml'lcr. Rcccntly. mcasurcmcnt of plasma estriol by radioimmunoassay :\IATERIALS Ac\D :\IETI IODS tcchniqucs has supplantcd urinary dctcrminations duc to thc grcatcr scnsitivity and casc of sampk l'olkction of this ncwn ~1,\Tl :RtALS methodology (8). 6.7-l"lljEstronc sulfatc. ammonium salt (42 Ci/ mmol). 17- Vcry low third trimcstl·r l'striol c:-.cretion has hccn rHltl·d in 'l!Jprcgncnolonc sulfate. ammonium salt (10 Ci/mmol). and four dinical situations: fetal lkmisc i11 111cm. ancncl·phaly. hypo- 17-"I I jdchydrocpiandrostcronc sulfatc. ammonium salt (20 plasia of the fetal adrcnal glands. and ddicicncy of thc placcntal Ci/mmol) wcrc obtaincJ from New En!!Iand Nudcar. Boston. microsomal 3-{3-hydroxystcroid sulfatc sulfatasc ( 12) . \lass.; cstrone sulfatc. dchydrocpiandro~tcronc sulfatc. p-nitro- This lattcr. ccncticallv dctcrminl·d inborn crror of mctabolism catcchol sulfatc (dipotassium salt). and p-nitrophcnyl sulfate has rn·l·ntly hcl·n thc s"ubjcct of rnnsidnabk invcstigation bi:- (potassium salt) from Sigma Chcmical Co .• St. Louis. !\lo.; and causc of thc implications of this disordcr for thc undnstanding of prcgnenolonc sulfatc from Stnaloids. Inc.. Pawling. N. Y. 4- thc mcd1anisms of control of thc onsl'I of labor. \\'c havc \kthylumhcllikryl sulfatc was synthcsizcd by thc proccdurc of n:ccntly had thc opportunity to study tissUl'S and culturcd cdls Shcrman and Stanficld ( 2<,) and purificd according to thl· from an affcctcd prcgnancy. Our rcsults providc two important mcthod of Rindcrkncct cl al. (25). 8 114 STEROID SULFATASE DEFICIENCY 895 PLAS~IA ESTRIOL high pH was used to 11111111111ze any possible interference by arylsulfatases A and B. The reaction was terminated with Plasma cslriol was measured by a sensitive radioimmunoassay the addition technique (22) . of 0.--1 ml I N KOi i and the product formed was estimated spcctrophotornctrically at 420 11111 . TISSUES Control and patient placentas were examined in the delivery PLACENTAL ARYI.SULFATASFS A AND II room, placed immediately on ice and were processed within 2 hr. Each placenta was extensively washed to free it of adhering The extract and pellet were examined by a modification of the blood.and a I 00-g portion was homogenized in a \Va ring Blcn­ arylsulfatasc A specific assay with p-nitrocatcchol sulfate of dor with I SO ml cold water. The homogenate was centrifuged at I3aum er al. O. 28). The extract was also subjected to chroma­ 16,300 x g for IS min. The supernatant lluid ( 130 ml) was tography on DEAE-ccllulose to separate arylsulfatase A from removed and designated "extract." The precipitated material arvlsulfatasc Band the fractions were assayed with 4-mcthvlum- was suspended in 130 ml water and designated "pellet." Protein bc.llifcryl sulfate as substrate (27). · · estimations of the extract and pellet were made by the procedure of Lowry ct 11!. ( 18). The remainder of tissue was frozen . En­ FIBROBLAST AND AMNIOTIC FLUID CELL ENZYME ACTIVITIES zyme preparations from the latter gave identical results as the Cells were harvested hy trypsinization and disrupted by freez­ freshly prepared material. The control placenta was obtained ing and thawing followed by gentle homogenization in a small from a woman with an uncomplicated pregnancy and normal glass homogenizer. Dehydrocpiandrostcrone (DIIEAS) sulfa­ delivery at term . lase activity was determined by incubation of up to I 00 µI homogenate in 0.1 M Tris-llCl buffer. pH 7.2. Substrate was CELL CULTURE STUDIES present at a concentration of 4 x Io<• Mand a specific activity of IS Ci/11101 . The final volume was 250 µl and incubation I luman fibroblast lines were established from the proband. was carried out at 37° for up to 4 hr. The amount of DHEAS the parents. a single unaffected male sibling. six controls. and dcsulfatcd was determined in the same fashion as for the from a variety of patients with known inborn errors of metabo­ placen­ tal enzymes. Arylsulfatase A and B levels were determined lism. In addition. amniotic fluid cells from pregnancies of 16-18 as for the placenta. 1:i:,5 :\_lucopolysaccharide turnover studies were weeks' duration and 34-37 weeks' duration were established as I done as described by Cantz ct al. were similar cultures derived from an amniocentesis just before (6). the proband's birth . All cultures were maintained in Eagle's minimum essential medium with I 0 % fetal calf scrum and were RESULTS examined at similar times after subculturing at equivalent popu­ lation densities. PLASI\IA ESTRIOL Plasma cstriol was undetectable at 35 and 3(, weeks' gestation. PLACENTAL STEROID SULFATASE ACTIVITY At 37 and 38 weeks. the values were 4 .8 nl!/ml and 3.S nl!/ ml. respectively . The sensitivity of the assay is 2.0 ng/ml. The-nor­ Identical assay procedures were used for cstronc sulfatasc. mal lcvd at 38 weeks' gestation is 18 ng/ ml ::!:: 7.S (::!::2 SD) (22).
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