Context P450 oxidoreductase deficiency (PORD) is a rare genetic disorder that is associated with significant morbidity. However there has been limited analysis of reported PORD cases. Objective To determine, based on the cohort of reported PORD cases, genotype-phenotype relationships for skeletal malformations, maternal virilisation in pregnancy, adrenal insufficiency, and disorders of sexual development (DSD). Data Sources PubMed and Web of Science from January 2004 to February 2018. Study Selection Published case reports/series of patients with PORD. Eligible patients were unique, had biallelic mutations, and their clinical features were reported. Data Extraction Patient data were manually extracted from the text of case reports/series. A malformation score, representing the severity of skeletal malformations, was calculated for each patient. Data Synthesis Of the 211 patients published in the literature, 90 were eligible for inclusion. More than 60 unique mutations were identified in this cohort. Four groups of mutations were identified, through regression modeling, as having significantly different skeletal malformation scores. Maternal virilization in pregnancy, reported for 21% of patients, was most common for R457H mutations. Adrenal insufficiency occurred for the majority of patients (78%) and was typically mild, with homozygous R457H mutations being the least deficient. DSD affected most patients (72%), but were less common for males (46XY) with homozygous R457H mutations. Conclusions PORD is a complex disorder with many possible mutations affecting a large number of enzymes. By analyzing the cohort of reported PORD cases, this study identified clear relationships between genotype and several important phenotypic features.

Prehospital and in-hospital management of children with CAH can vary between health services. Children under 12 months have lower levels of stress dosing prior to hospital than other age groups. Experience with acute episodes improves self-management of CAH in the context of acute illness in educated patient populations.

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Background/Aims: To determine the burden of hospitalisation in children with adrenal insufficiency (AI)/hypopituitarism in Australia. Methods: A retrospective study of Australian hospitalisation data. All admissions between 2001 and 2014 for patients aged 0–19 years with a principal diagnosis of AI/hypopituitarism were included. Denominator populations were extracted from national statistics datasets. Results: There were 3,779 admissions for treatment of AI/hypopituitarism in patients aged 0–19 years, corresponding to an average admission rate of 48.7 admissions/million/year. There were 470 (12.4%) admissions for an adrenal crisis (AC). Overall, admission for AI/hypopituitarism was comparable between the sexes. Admission rates for all AI, hypopituitarism, congenital adrenal hyperplasia (CAH), and “other and unspecified causes” of AI were highest among infants and decreased with age. Admissions for primary AI increased with age in both sexes. Males had significantly higher rates of admission for hypopituitarism. AC rates differed by both sex and age group. Conclusion: This nationwide study of the epidemiology of hospital admissions for a principal diagnosis of AI/hypopituitarism shows that admissions generally decreased with age; males had higher rates of admission for hypopituitarism; females had higher rates of admission for CAH and “other and unspecified causes” of AI; and AC incidence varied by age and sex. Increased awareness of AI and AC prevention strategies may reduce some of these admissions.

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