Primary adrenal insufficiency in patients with CPOX gene mutations
European Journal of Endocrinology, cilt.192, sa.5, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 192 Sayı: 5
- Basım Tarihi: 2025
- Doi Numarası: 10.1093/ejendo/lvaf089
- Dergi Adı: European Journal of Endocrinology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
- Anahtar Kelimeler: children, CPOX, mitochondria, porphyria, primary adrenal insufficiency
- İstanbul Üniversitesi Adresli: Evet
Özet
Background: Harderoporphyria arises from biallelic CPOX gene mutations, leading to coproporphyrinogen oxidase deficiency in the inner mitochondrial membrane. The impact of CPOX gene mutations on adrenal function remains poorly understood. Objective: Characterizing primary adrenal insufficiency (PAI) in 2 siblings with harderoporphyria. Methods: Clinical data were recorded, and genetic analysis was performed by whole genome sequencing (WGS). Plasma steroids and urinary porphyrins were measured by liquid chromatography-mass spectrometry and high-performance liquid chromatography, respectively. Mitochondrial function was assessed using the mitochondrial membrane potential (MMP) assay in peripheral blood mononuclear cells. Results: Patients were diagnosed with PAI at 4.5 years (P1, 46,XY) and 7 months (P2, 46,XX). P1 had atypical genitalia and developed primary gonadal insufficiency and non-immune diabetes at ages 6 and 10, respectively. Both patients had a history of microcytic anaemia, haemolysis, cholestasis, hepatosplenomegaly in early infancy, hyperpigmentation, abdominal pain, nystagmus, optic atrophy, and mild lactic acidosis in early childhood. WGS revealed a homozygous c.83_85del, p.S28* variant in CPOX. Oxidative damage to mitochondria was shown by decreased MMP in patients compared with controls (P < .0001). Hormonal assessment indicated severe PAI, suggestive of combined CYP11A1 and CYP11B1 deficiency. Conclusions: CPOX gene mutations cause a mixed model of PAI, affecting mitochondrial steroidogenic enzymes. Clinical manifestations of harderoporphyria may overlap with PAI signs.