Cytochrome POR deficiency

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Classification according to ICD-10
E25.0 Adrenogenital disorders
ICD-10 online (WHO version 2019)

The cytochrome POR deficiency is a very rare congenital form of congenital adrenal hyperplasia with the main features of a lack of glucocorticoids , pronounced intersexuality in both sexes and skeletal malformations, especially of the head and face.

Synonyms are: adrenal hyperplasia, congenital, due to cytochrome POR deficiency; POR deficiency; PORD; Antley-Bixler-like syndrome; English Antley-Bixler syndrome with disordered steroidogenesis; combined partial deficiency of 17-hydroxylase and 21-hydroxylase; Congenital adrenal hyperplasia due to apparent combined p450c17 and p450c21 deficiency

The first description comes from 1985 by the US doctors Ralph E. Peterson, Julianne Imperato-McGinley, Teofilo Gautier and Cedric Shackleton.

distribution

The frequency is given as 1 in 100,000 - 200,000 live births, so far about 65 people have been reported. Inheritance is autosomal - recessive .

root cause

Of the disease are mutations in the POR - gene on chromosome 7 locus q11.23 basis that (reductase Cytochrome P450, P450 or the cytochrome oxidoreductase NADPH cytochrome P450 oxidoreductase ) coded. The disorder results in a combined deficiency of P450C17 and P450C21 and an accumulation of metabolites for steroid production .

Clinical manifestations

Clinical criteria are:

The extent of the changes ranges from the intersexual genitalia with adrenal insufficiency and skeletal malformations to milder forms with changes such as in polycystic ovary syndrome . Often amenorrhea and infertility

The increased androgen intrauterine leads to pronounced virilization in the female sex and inhibited virilization in the male sex with micropenis to perineal hypospadias

Facial dysmorphism with a flat nose, balcony forehead, hypoplasia of the midface, craniofacial malformations in patients are craniosynostosis , hydrocephalus , large balcony forehead, flat nose, midface hypoplasia , protruding eyes (proptosis) and dysplastic auricle , narrow external auditory canal

Furthermore arachnodactyly , synostosis , choanal , decreased cortisol levels , increased mineralocorticoids with hypertension , Virilisationszeichen the mother during pregnancy , fractures in the newborn, congenital bowing of long bones, clubfoot occur.

Differential diagnosis

Must be distinguished are the Williams Syndrome and Antley-Bixler syndrome .

therapy

The treatment consists of lifelong hormone replacement therapy , if necessary, surgery for craniosynostosis, hypospadias, cryptorchidism or vaginal hypoplasia and clitoral hypertrophy .

literature

  • WL Miller: P450 oxidoreductase deficiency: a disorder of steroidogenesis with multiple clinical manifestations. In: Science signaling. Vol. 5, No. 247, October 2012, pp. Pt11, doi: 10.1126 / scisignal.2003318 , PMID 23092891 (Review).
  • M. Fukami, T. Ogata: Cytochrome P450 oxidoreductase deficiency: rare congenital disorder leading to skeletal malformations and steroidogenic defects. In: Pediatrics international: official journal of the Japan Pediatric Society. Vol. 56, No. 6, December 2014, pp. 805-808, doi: 10.1111 / ped.12518 , PMID 25294558 (Review).
  • CE Flück, T. Tajima, AV Pandey, W. Arlt, K. Okuhara, CF Verge, EW Jabs, BB Mendonça, K. Fujieda, WL Miller: Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. In: Nature genetics. Vol. 36, No. 3, March 2004, pp. 228-230, doi: 10.1038 / ng1300 , PMID 14758361 .

Individual evidence

  1. ↑ a b c d Adrenal hyperplasia, congenital, due to cytochrome P450 oxidoreductase deficiency. In: Orphanet (Rare Disease Database).
  2. ↑ a b J. Idkowiak, D. Cragun, RJ Hopkin, W. Arlt: Cytochrome P450 Oxidoreductase Deficiency. In: MP Adam, HH Ardinger, RA Pagon, SE Wallace, LJH Bean, K. Stephens, A. Amemiya (editors): GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2018, 2005 Sep 8 [updated 2017 Aug 3]. PMID 20301592
  3. ^ RE Peterson, J. Imperato-McGinley, T. Gautier, C. Shackleton: Male pseudohermaphroditism due to multiple defects in steroid-biosynthetic microsomal mixed-function oxidases. A new variant of congenital adrenal hyperplasia. In: The New England Journal of Medicine . Vol. 313, No. 19, November 1985, pp. 1182-1191, doi: 10.1056 / NEJM198511073131903 , PMID 2932643 .
  4. ↑ a b Genetics Home Reference
  5. ↑ Disordered steroidogenesis due to cytochrome P450 oxidoreductase.  In: Online Mendelian Inheritance in Man . (English)