Elevated Phenylalanine Levels Due to Inhaled Steroids in Phenylketonuria

Document Type

Conference Proceeding

Publication Date

5-2026

Publication Title

American Journal of Respiratory and Critical Care Medicine

Abstract

Phenylketonuria (PKU) is a metabolic disorder caused by phenylalanine (Phe) hydroxylase deficiency leads to the inability to break down Phe causing developmental and neurologic sequelae. Some medications can elevate Phe above safe levels. We discuss a case of difficult to control asthma in a child with PKU. The patient, diagnosed with PKU shortly after birth, developed asthma symptoms by age two. Initial treatment with intermittent inhaled corticosteroids (ICS) provided symptom relief, but asthma control fluctuated over time, requiring escalation to daily ICS therapy. However, the patient’s parents noticed serum Phe levels monitored at home increased when using daily ICS (Figure 1), raising concerns about steroid effects on Phe metabolism. This pattern continued every time the ICS was used. Literature suggests systemic corticosteroids promote a catabolic state, increasing protein breakdown and potentially elevating Phe levels. This both led to frequent cessation of ICS but also caused parents and physicians to avoid using systemic corticosteroids leading to dangerous and difficult to control exacerbations. Additionally, viral illness, the most common trigger for asthma exacerbations, also raises Phe levels. While ICS are designed for localized pulmonary action, a significant portion is swallowed and absorbed systemically, potentially contributing to metabolic effects. Switching to ciclesonide, a prodrug activated in the lungs with lower systemic bioavailability, resulted in improved asthma control and normalization of Phe levels. This case suggests a potential link between ICS use and elevated Phe levels in PKU patients, though this relationship is not well studied. Emerging metabolomic research in asthma reveals altered amino acid pathways, including Phe metabolism, further supporting interaction between asthma, its treatment and PKU. Our experience suggests more research is needed to assess the safety of ICS in children with PKU and ciclesonide may be the safest first line therapy for the management of asthma in children with PKU.

Volume

212

Issue

Suppl 1

First Page

S263

Last Page

S263

Comments

American Thoracic Society International Conference, May 15-20, 2026, Orlando, FL

Helen DeVos Children’s Hospital

DOI

10.1093/ajrccm/aamag162.368

ISSN

1073-449X

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