CoChat
Sign Up
Cited by 6Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

Isolated 17, 20–lyase deficiency secondary to a novel CYB5A variant: comparison of steroid metabolomic findings with published cases provides diagnostic guidelines and greater insight into its biological role

Shaunak, Meera, Taylor, Norman F., Hunt, David, Davies, Justin H.·2020·Hormone Research in Paediatrics
DOI 10.1159/000512372
Open this paper in CoChat — free account

Abstract

OBJECTIVE: The objective of this study was to report CYB5A deficiency, to discuss the contribution of steroid metabolomics to diagnosis and interpretation, and to highlight the presence of testicular microlithiasis. METHODS: Two siblings with ambiguous genitalia at birth were later found to carry novel CYB5A variants, with resulting isolated 17, 20 lyase deficiency. We compared urine steroid data obtained between birth and adulthood with that from other cases. RESULTS: Neonatal urine steroid profiles show a relative increase of 16-hydroxylated pregnenolone metabolites. Thereafter, there are no distinguishing features until puberty, when sex steroid deficiency drives gonadotrophin production, resulting in marked increases of 17-hydroxyprogesterone metabolites derived from the gonads. This excess may be revealed pre-pubertally by gonadotrophin stimulation testing. Novel findings are first, a considerable capacity for DHEA synthesis in the neonatal period compared to childhood and adulthood, suggesting that DHEAS production is much less dependent on CYB5A at birth; second, no consistent change in "backdoor pathway" intermediates; third, side chain cleavage of cortisol is largely unaffected, supporting the existence of a different lyase not dependent on CYB5A; fourth, increased 17-hydroxyprogesterone metabolites and very low androgen metabolites are diagnostic post-pubertally. CONCLUSION: This is the fourth disease-causing variant in CYB5A in isolated 17, 20 lyase deficiency and the first associated with testicular microlithiasis. Establishing a biochemical diagnosis pre-pubertally should now be possible using urine steroid profiling, supported by synacthen and gonadotrophin stimulation testing. We recommend liquid chromatography-mass spectrometry/mass spectrometry rather than immunoassay for serum steroid analysis, early methaemoglobin measurement and surveillance should testicular microlithiasis be detected.

Integrity signals

Registry

Crossref · 10.1159/000512372

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A small number of reports have described b5 deficiency in patients with apparent isolated 17,20-lyase deficiency, sometimes associated with methemoglobinemia.

    “Since then, a small number of reports have described b5 deficiency in patients with apparent isolated 17,20-lyase deficiency, sometimes associated with methemoglobinemia ( 11 , 12 , 54 ).”

    From Disordered Electron Transfer: New Forms of Defective Steroidogenesis and Mitochondriopathy (2025) · cites this paper as [54]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Shaunak, M., Taylor, N. F., Hunt, D., & Davies, J. H.
Affiliations
  • University Hospital Southampton NHS Foundation Trust (GB)
  • King's College Hospital (GB)
ORCID
Davies, Justin H.
Venue
Hormone Research in Paediatrics
Publisher
S. Karger AG
Published
2020
Volume
93
Issue
7-8
Pages
483-496
ISSN
  • 1663-2818 (ISSN-L)
  • 1663-2826
DOI
10.1159/000512372
OpenAlex
W3130475684
Cited by
6
References
19
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1
FWCI
0.24
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Hormone Research in Paediatrics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
17,20-lyase deficiency, CYB5A, testicular microlithiasis, ambiguous genitalia, 17-hydroxyprogesterone, congenital adrenal hyperplasia
MeSH terms
Adrenal Hyperplasia, Congenital, Androgens, Calculi, Female, Humans, Infant, Newborn, Male, Disorders of Sex Development, Steroid 17-alpha-Hydroxylase, Steroids, Testicular Diseases, Cytochromes b5, Metabolomics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review