PKU Flashcards
A 3-day-old infant is brought to the pediatrician for a routine newborn screening follow-up. The infant was born at term and initially appeared healthy. However, the screening test revealed elevated phenylalanine levels. The parents report no significant symptoms but mention a musty odor from the baby’s diapers. Which of the following is the most appropriate next step in managing this patient?
A) Start a phenylalanine-restricted diet and tyrosine supplementation
B) Prescribe folate and vitamin B12 supplementation
C) Initiate a high-protein diet to prevent hypoglycemia
D) Avoid all foods containing tyrosine and phenylalanine
E) Delay intervention until confirmatory genetic testing is completed
Answer: Start a phenylalanine-restricted diet and tyrosine supplementation
Explanation: Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency in phenylalanine hydroxylase or its cofactor tetrahydrobiopterin (BH4), resulting in elevated phenylalanine levels. Early diagnosis through newborn screening and prompt dietary management are crucial to prevent intellectual disability, seizures, and other complications. Treatment includes restricting phenylalanine intake while ensuring adequate tyrosine supplementation, as tyrosine becomes an essential amino acid in PKU.
Incorrect Answers:
B) Folate and vitamin B12 supplementation are not indicated for PKU but are used to manage megaloblastic anemia.
C) A high-protein diet would worsen phenylalanine accumulation in PKU.
D) Avoiding tyrosine would exacerbate deficiencies, as tyrosine is essential for neurotransmitter synthesis in PKU.
E) Intervention should not be delayed, as early dietary treatment is critical to prevent irreversible neurologic damage.
A 2-month-old male infant is brought to the pediatric clinic for a well-baby checkup. The mother reports that the baby has been irritable and is feeding poorly. On examination, the infant has microcephaly, a low birth weight, congenital heart defects, and a characteristic musty odor. The mother mentions that she was diagnosed with phenylketonuria (PKU) as a child but stopped dietary restrictions after adolescence. Which of the following is the most likely explanation for this infant’s condition?
A) Elevated maternal phenylalanine levels during pregnancy
B) Inherited deficiency of phenylalanine hydroxylase from both parents
C) Congenital infection with cytomegalovirus (CMV)
D) Folate deficiency during pregnancy
E) Neonatal deficiency of tetrahydrobiopterin (BH4)
Answer: Elevated maternal phenylalanine levels during pregnancy
Explanation: Maternal PKU syndrome occurs when a pregnant woman with untreated PKU has elevated phenylalanine levels, which are teratogenic to the developing fetus. High maternal phenylalanine levels cross the placenta and impair fetal development, leading to congenital anomalies such as microcephaly, intellectual disability, growth restriction, congenital heart defects, and the characteristic musty odor. The risk can be mitigated by strict dietary control of phenylalanine levels before and during pregnancy.
Incorrect Answers:
B) While PKU is an autosomal recessive disorder, this infant’s condition is due to maternal PKU syndrome, not inheritance of the enzyme deficiency.
C) CMV infection can cause microcephaly and low birth weight but would not explain the musty odor or congenital heart defects.
D) Folate deficiency during pregnancy can lead to neural tube defects but is unrelated to PKU.
E) BH4 deficiency affects phenylalanine metabolism in the neonate but does not explain the findings associated with maternal PKU.
What is the genetic inheritance pattern of Phenylketonuria (PKU)?
Autosomal recessive
What enzyme deficiency causes classical PKU?
Deficiency of phenylalanine hydroxylase (PAH).
rarely from a BH4 (tetrahydrobiopterin cofactor) deficiency.
What cofactor deficiency can mimic PKU and lead to similar clinical findings?
Deficiency of tetrahydrobiopterin (BH4), a cofactor for phenylalanine hydroxylase
What are the main clinical features of untreated PKU?
- Intellectual disability
- Microcephaly
- Seizures
-Ataxia - Hypopigmented skin
- eczema
- musty body odor
What are the two most common features in patients who have PKU?
musty odor and seizures
in approx. 50% of patients.
What causes hypo pigmentation in patients with PKU?
Hypopigmentation (irises, hair, and skin) occurs because tyrosine is a precursor to melanin and these patients have an inability to synthesize tyrosine.
What is maternal PKU syndrome, and how can it be prevented?
High phenylalanine levels during pregnancy can lead to fetal growth restriction, microcephaly, intellectual disability, and congenital heart defects. Prevention requires strict dietary control of phenylalanine during pregnancy. Can be prevented with dietary measures.
What are the key findings in PKU on laboratory testing?
- Elevated phenylalanine levels, phenyl ketones (phenylacetate, phenyllactate, phenylpyruvate) in urine, and musty body odor.
- Usually found on neonatal screens. Screening occurs 2–3 days after birth (normal at birth because of maternal enzyme during fetal life).
- Confirmation with genetic analysis.
What might prevent a newborn screen in a community that has access to medical resources?
newborn screening can only be refused if it is in conflict with the parents’ religious practices or beliefs.
What dietary modifications are essential for managing PKU?
Reduce phenylalanine intake and supplement tyrosine. Include foods such as soy products, chicken, fish, and milk. BH4 supplementation may be necessary in BH4 deficiency.
Patients can be given enzyme replacement therapy.
What artificial sweetener must patients with PKU avoid, and why?
Aspartame, because it contains phenylalanine.
what is the prognosis for patients with PKU?
With early intervention, the prognosis is good.
Untreated patients typically die in infancy.
