Phenylketonuria (NORD)

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Phenylketonuria (NORD)



Phenylketonuria (NORD)


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USMLE® Step 1 questions

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Phenylketonuria (NORD)

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A 22-year-old primigravida at 26 weeks gestation comes to the office for routine prenatal care. The patient reports good fetal movement and has no complaints. She has been inconsistent with prenatal care following her initial visit at 12 weeks. An ultrasound for gestational dating at the time was consistent with her last menstrual period. The mother’s blood group is B-negative while the father’s is O-negative. The patient’s past medical history is significant for phenylketonuria. Prior to conceiving, she followed a phenylalanine-restricted diet. Temperature is 37.0°C (98.6°F), pulse is 92/min, respirations are 20/min, and blood pressure is 105/75 mmHg. An ultrasound reveals a fetus at 26 weeks with an estimated weight <10 percentile for gestational age. Laboratory evaluation reveals elevated phenylalanine levels. Which of the following pathologies is the fetus likely to suffer from based on the maternal history? 

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phenylketonuria p. 81

Congenital heart disease p. 304-306

maternal phenylketonuria p. 82


phenylketonuria p. 82


maternal phenylketonuria p. 82

Phenylketonuria p. 82, 82

Pregnancy p. 657

maternal phenylketonuria p. 81

Seizures p. 535

phenylketonuria p. 82


Phenylketonuria or PKU is a rare metabolic disease that can lead to severe brain disorders caused by the accumulation of the amino acid phenylalanine to toxic levels in the blood and brain.

Amino acids are the basic building blocks that make up proteins. Phenylalanine, or Phe, is one of the essential amino acids.  It is necessary for life, but our bodies can't make it; therefore, Phe must be acquired through foods that contain protein. Normally, once Phe enters the body, most of it is converted to tyrosine by the enzyme phenylalanine hydroxylase. Tyrosine is then turned into neurotransmitters important for normal brain development and function.

PKU is an autosomal recessive genetic disorder that affects function of the phenylalanine hydroxylase enzyme. The phenylalanine hydroxylase gene is located on chromosome 12 and over 600 mutations have been described. The degree of enzyme function can vary. When untreated, people with PKU develop symptoms such as severe intellectual disability, psychiatric disorders, and seizures. A pregnant woman with PKU must pay special attention to her Phe levels to reduce the risk of Maternal PKU Syndrome that can result in heart defects, microcephaly, and developmental disability in her baby.

In PKU, elevated Phe levels and reduced tyrosine levels can change the way the brain functions. This is because Phe uses the same transporters to get across the blood-brain barrier as other amino acids including- tyrosine and tryptophan. Tyrosine is needed to synthesize dopamine and norepinephrine, and tryptophan is needed to synthesize the neurotransmitter serotonin. As Phe levels rise, it occupies all the transporters, making it hard for tyrosine and tryptophan to get across the blood-brain barrier. As a result, dopamine, norepinephrine, and serotonin levels in the brain begin to fall, leading to abnormal brain development and intellectual disability.


Phenylketonuria (PKU) is an autosomal recessive amino acid metabolism disorder involving impaired metabolism of the amino acid phenylalanine, caused by the absence or reduced activity of phenylalanine hydroxylase. In PKU toxic levels of phenylalanine and phenylketone build up in the body and tyrosine levels drop.

Symptoms include a musty odor of sweat and urine, intellectual disability, seizures, behavioral problems, and other neurological symptoms. In pregnant females, PKU can affect the fetus - causing heart disease, growth problems, intellectual disability, and microcephaly. Treatment is based on a diet with low levels of phenylalanine and supplementing with tyrosine and tetrahydrobiopterin.


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