Clinical Guidance

The natural history of cytochrome P450 oxidoreductase deficiency (PORD) varies because it encompasses a wide phenotypic spectrum. However, steroid abnormalities, which occur in all individuals with PORD, can be associated with a number of characteristics. The summary of clinical characteristics is based on 26 studies on 140 individuals with molecularly confirmed PORD published to date (June 2017). Cortisol deficiency found in PORD varies, but is present in the majority of individuals. Based on ACTH stimulation tests, reported severe cortisol deficiency (requiring permanent hydrocortisone replacement) in 43% of individuals, and partial cortisol deficiency (requiring glucocorticoid replacement during stress only) in 40%; no replacement was required in 10% of the cohort.

Diagnostic Criteria

Suggestive Findings

Cytochrome P450 oxidoreductase deficiency (PORD) is an autosomal recessive disorder with a broad phenotypic spectrum including skeletal malformations resembling the Antley-Bixler syndrome (ABS) phenotype and abnormalities in adrenal steroid biosynthesis resulting in congenital adrenal hyperplasia (CAH).

Clinical Findings

Skeletal abnormalities. PORD should be suspected in individuals with features of ABS. Affected individuals may present with the following congenital craniofacial and skeletal anomalies:

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PORD, the following evaluations are recommended:

• Evaluations by appropriate specialists in endocrinology, clinical genetics, neurosurgery, otolaryngology, and cardiology

Surveillance Guidelines

Individuals with PORD should be seen by a specialist tertiary pediatric endocrine service throughout childhood to closely monitor their development and adjust steroid supplementation. Because of the presence of developmental delays in many individuals with ABS, periodic formal developmental assessments may be indicated. However, interpretation of these assessments may be complicated by the physical limitations of the disorder. Screening evaluations are likely to underestimate cognitive abilities. Therefore, evaluations should be done in centers with expertise and experience in developmental testing.