Prenatal diagnosis ofthree cases ofsevere combined immunodeficiency: severe Tcell deficiency during thefirst half ofgestation infetuses withadenosine deaminase deficiency

SUMMARY Theprenatal diagnosis ofsevere combined immunodeficiency (SCID) wasmadeinthree fetuses bystaining fetal bloodobtained atfetoscopy witha panel ofmonoclonal antibodies. Therewereless than100T cells/mm3 offetal bloodinthese three cases compared to2,500/mm3 in14immunologically normal fetuses. Cells bearing thecortical thymocyte antigen (NA1/34) werenotdetected inanyofthenormal oraffected fetal blood samples. Twooftheaffected fetuses werealso homozygous foradeficiency ofadenosine deaminase (ADA)with undetectable levels ofredcell ADA.Allthree affected fetuses were aborted andpostmortem tissue wasobtained intwocases. Inbothofthese cases the thymus wasmarkedly hypoplastic andcontained nolymphoid cells. Oneofthese fetuses washomozgous forADA deficiency andthevirtual absence ofTcells orthymocytes during thesecond trimester ofpregnancy indicates that placental access tothematernal circulation doesnotprevent damagetotheTlineage stemcells inthis disease. Prenatal diagnosis ofSCIDhaspreviously onlybeenpossible inpatients withadefined metabolic defect suchasADA deficiency, butthese studies indicate that prenatal diagnosis nowmay beoffered formostatrisk pregnancies.