Congenital Phenylketonuria (PKU)
Phenylketonuria (PKU) is an inborn error of metabolism that, if left untreated, causes severe developmental delay. Infants with PKU lack phenylalanine hydroxylase, an enzyme necessary to convert phenylalanine, a dietary amino acid which can not be metabolized by the body, into tyrosine. The unused phenylalanine and it's associated by-products accumulate in the blood stream, resulting in impaired development of the central nervous system.
A simple blood test can detect elevated phenylalanine levels in newborn infants, and in most western countries babies are tested for PKU at birth. For most individuals with PKU, careful restriction of phenylalanine in the diet prevents devastating nervous system defects. However, a small minority of PKU patients suffer from a condition called tetrahydrobiopterin deficiency, which does not respond to dietary modifications. Individuals with this condition, as well as those with inadequately managed or misdiagnosed PKU, are subject to progressive neurological impairment including microcephaly, hyperactivity, severe developmental delay, hypotonia, rigidity, and seizures. Secondary respiratory infections are common.
Airway clearance indications which may be present in congenital PKU include:
- Poor muscle coordination, sensory impairment, and seizures can all result in impaired swallowing, increasing risk for aspiration and consequent pulmonary infection
- Because saliva and gastric contents contain bacteria, aspiration introduces microorganisms into normally sterile airways. Ineffective secretion clearance associated with recurrent aspiration, places patients with uncontrolled PKU at high risk for hosting a vicious cycle of mucus obstruction, infection, and progressive, irreversible lung damage.
- Inadequate control of respiratory muscles due to enervation or hypotonia can impair the normal cough reflex and, as a result, interfere with the ability to clear aspirated material and pulmonary secretions from the airways.
- Retained secretions provide a cultural medium for bacterial pathogens. Consequent infections produce still more mucus, initiating a vicious cycle of mucus obstruction, recurrent bouts with pneumonia, bacterial colonization, progressive pulmonary compromise and, finally, respiratory failure.
Aggressive bronchial hygiene, including daily Airway Clearance Therapy, is an essential component in the management of patients with pulmonary complications from congenital PKU. Conscientious attention to daily secretion clearance may prevent or minimize the pulmonary complications associated with this disorder.
The hyperphenylalaninemias. In: Fauci AS, Braunwald E, Isselbacher KJ, et al. Harrison's Principles of Internal Medicine. 14th edition. New York, NY: McGraw-Hill Book Co; 1998:2198-2199.
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