title: Severe Salt-Losing 3β-Hydroxysteroid Dehydrogenase Deficiency: Treatment and Outcomes of HSD3B2 c.35G>A Homozygotes.
abstract: BACKGROUND
  3-β-hydroxysteroid dehydrogenase (HSD3B2) deficiency accounts for less than 5% of congenital adrenal hyperplasia worldwide, but is relatively common among the Old Order Amish of North America due to a HSD3B2 c.35G>A founder mutation.
  
  
  OBJECTIVE
  We review clinical presentation, disease course, treatment, and outcomes of a genetically homogenous population of HSD3B2-deficient patients.
  
  
  METHODS
  This was a retrospective case series: anthropometric, biochemical, and clinical data from 16 (six male) affected subjects (age, 7.2 ± 6.4 y) were compared to reference data from 12 age-matched unaffected siblings.
  
  
  METHODS
  The setting was the Clinic for Special Children, a nonprofit rural community health center in Lancaster, Pennsylvania.
  
  
  METHODS
  The main outcome measures were growth, skeletal maturation, sexual development, blood pressure, glucocorticoid dose, pituitary-adrenal homeostasis, and long-term morbidity.
  
  
  RESULTS
  Exogenous glucocorticoid requirement was dichotomous: a standard-dose group (n = 9) required 15.4 ± 4.9 mg/m(2)/d hydrocortisone equivalent, whereas a high-dose group required much larger and more variable doses (hydrocortisone equivalent, 37.8 ± 15.4 mg/m(2)/d) (P < .0001). Despite glucocorticoid doses 2-fold higher than the standard-dose group, high-dose patients: 1) had ACTH, 17-hydroxypregnenolone, and dehydroepiandrosterone levels that were 10-fold, 20-fold, and 20-fold higher, respectively; 2) were exclusively affected by signs of sex steroid excess; and 3) tended to have more iatrogenic complications.
  
  
  CONCLUSIONS
  Patients with HSD3B2 deficiency and 21-hydroxylase deficiency suffer similar morbid complications from under- and overtreatment, but HSD3B2 deficiency is associated with a distinctive pattern of sex steroid dysmetabolism. Disease- and treatment-related morbidities are almost exclusively observed among subjects who have a high exogenous glucocorticoid requirement.
authors.affiliation: Clinic for Special Children (A.R.B., M.Y., D.R., C.H., K.A.S.), Strasburg, Pennsylvania 17579; Department of Pediatric Endocrinology (P.A.L.), Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033; Franklin and Marshall College (K.A.S.), Lancaster, Pennsylvania 17603; and Lancaster General Hospital (K.A.S.), Lancaster, Pennsylvania 17602.
authors.forename: Abigail R
authors.initials: AR
authors.lastname: Benkert
authors.affiliation: Clinic for Special Children (A.R.B., M.Y., D.R., C.H., K.A.S.), Strasburg, Pennsylvania 17579; Department of Pediatric Endocrinology (P.A.L.), Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033; Franklin and Marshall College (K.A.S.), Lancaster, Pennsylvania 17603; and Lancaster General Hospital (K.A.S.), Lancaster, Pennsylvania 17602.
authors.forename: Millie
authors.initials: M
authors.lastname: Young
authors.affiliation: Clinic for Special Children (A.R.B., M.Y., D.R., C.H., K.A.S.), Strasburg, Pennsylvania 17579; Department of Pediatric Endocrinology (P.A.L.), Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033; Franklin and Marshall College (K.A.S.), Lancaster, Pennsylvania 17603; and Lancaster General Hospital (K.A.S.), Lancaster, Pennsylvania 17602.
authors.forename: Donna
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Clinic for Special Children (A.R.B., M.Y., D.R., C.H., K.A.S.), Strasburg, Pennsylvania 17579; Department of Pediatric Endocrinology (P.A.L.), Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033; Franklin and Marshall College (K.A.S.), Lancaster, Pennsylvania 17603; and Lancaster General Hospital (K.A.S.), Lancaster, Pennsylvania 17602.
authors.forename: Christine
authors.initials: C
authors.lastname: Hendrickson
authors.affiliation: Clinic for Special Children (A.R.B., M.Y., D.R., C.H., K.A.S.), Strasburg, Pennsylvania 17579; Department of Pediatric Endocrinology (P.A.L.), Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033; Franklin and Marshall College (K.A.S.), Lancaster, Pennsylvania 17603; and Lancaster General Hospital (K.A.S.), Lancaster, Pennsylvania 17602.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Lee
authors.affiliation: Clinic for Special Children (A.R.B., M.Y., D.R., C.H., K.A.S.), Strasburg, Pennsylvania 17579; Department of Pediatric Endocrinology (P.A.L.), Pennsylvania State University Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033; Franklin and Marshall College (K.A.S.), Lancaster, Pennsylvania 17603; and Lancaster General Hospital (K.A.S.), Lancaster, Pennsylvania 17602.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011375:Progesterone Reductase / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014883:Water-Electrolyte Imbalance / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D055815:Young Adult
chemical_list: C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase