Disease Description (Causes and Symptoms):
- Definition/Cause: Phenylketonuria (PKU) is an autosomal recessive inherited metabolic disorder caused by a deficiency of phenylalanine hydroxylase (PAH), the enzyme that converts phenylalanine to tyrosine, or an abnormality in the biosynthesis of the cofactor BH4 (tetrahydrobiopterin). The PAH gene is located on chromosome 12. Classical PKU is caused by PAH deficiency, while atypical PKU is caused by deficiencies of BH4-related enzymes and others.
- Pathophysiology: Because phenylalanine cannot be broken down due to PAH deficiency or BH4 abnormalities, it accumulates in the blood and body, and toxic metabolites are produced, causing neurodevelopmental disorders.
- Main symptoms: Developmental delay (motor and language), intellectual disability, seizures, vomiting, eczema, hypopigmentation of the skin and hair (pale or light-colored), and a characteristic “mouse urine (musty)” odor of sweat and urine. If untreated, IQ declines during infancy (for example, if untreated until 1 year of age, IQ may be ≤50).
- Prevalence: Approximately 1/14,000 among White people and approximately 1/70,000–1/80,000 in East Asian populations, including Korea and Japan (approximate figures).
Treatment Methods:
- Basic principle: Prevent neurological damage by maintaining the blood phenylalanine concentration within the target range.
- Dietary therapy (main treatment): Start a low-phenylalanine or phenylalanine-restricted diet and special formula (low-phenylalanine protein substitute) early, if possible within 1 month after birth. During childhood, especially before 6 years of age, it is recommended to maintain blood Phe at approximately 3–8 mg/dL. Restrictions may be relaxed after age 6, but lifelong management is recommended, with a target of 3–15 mg/dL recommended after puberty.
- Medication:
- BH4 (sapropterin): Administered to patients who are responsive to BH4 (there are cases in which doses within the standard range of ≤20 mg/kg/day are used). Responsiveness is confirmed through testing.
- In atypical PKU (abnormal BH4 synthesis): Supplement BH4 and, when necessary, neurotransmitter precursors (e.g., L-DOPA, 5-HTP, etc.).
- Management related to maternal PKU: Maintain a low-phenylalanine diet before and during pregnancy and generally manage serum Phe at ≤10 mg/dL during pregnancy (to prevent fetal malformations, low birth weight, and intellectual disability).
- Monitoring: Regular blood phenylalanine testing (frequent measurements are needed during infancy: weekly or every other week; thereafter, every several weeks to monthly during childhood and adulthood), growth and neurodevelopmental assessments, nutritional status checks (paying attention to protein and vitamin deficiencies), and follow-up with a dietitian and metabolic specialist.
- Precautions (treatment considerations and risk of complications/self-management):
- Risk of neurological deterioration if the diet is discontinued (intellectual disability, seizures, etc.).
- Excessive phenylalanine restriction may cause growth retardation, anemia, and hypoproteinemia → balanced protein and nutritional supplementation is necessary.
- Responsiveness must be assessed when administering BH4 (it is not effective for everyone).
- Preconception counseling is essential (to prevent fetal risks associated with maternal PKU).
- Complications: Intellectual disability, seizures, behavioral and emotional problems, and pregnancy-related fetal malformations (if maternal management fails).
Checklist Before an Outpatient Visit (Including Example Questions):
- Items/information to prepare:
- Recent blood phenylalanine (Phe) level and test date (test report, if possible)
- List of currently used medications (such as sapropterin), vitamins, and nutritional supplements
- Current diet (foods and amounts consumed per day, and whether special formula or supplements are being used)
- Growth chart and developmental history (whether there has been motor or language delay), and seizure history
- Results of previous genetic or enzyme testing (if available)
- Whether pregnancy is planned or currently in progress
- Key items to check during the outpatient visit:
- Whether the blood Phe target range is being achieved and whether the testing frequency needs adjustment
- Need for dietary adjustment and nutritional status (iron, protein, etc.)
- Medication (such as sapropterin) responsiveness and adverse-effect testing
- Management plan for pregnancy planning or pregnancy
Example questions (items that are helpful for the patient to prepare for the outpatient visit):
- “What was my most recent blood phenylalanine level? How does it compare with the target range?”
- “Do the medications (or supplements) I am taking affect my blood phenylalanine level?”
- “I am planning a pregnancy. What should I prepare from now on?”
General Example Questions to Ask the Doctor:
- “What blood phenylalanine target level should I maintain? Does it vary by age?”
- “What should I adjust in my current diet, and how can I prevent nutritional deficiencies?”
- “Is sapropterin (or BH4) treatment appropriate for me, and what are its effects and side effects?”
- “How often should I have regular tests, and what changes in the results should prompt me to contact you immediately?”
- “What should I pay particular attention to if I am planning a pregnancy?”
Examples of Disease-Specific Questions:
- “What is my (or my child’s) genotype (PAH variant or BH4-related variant), and can BH4 responsiveness to treatment be expected based on it?”
- “I am planning a pregnancy. How should I specifically establish my blood phenylalanine targets and dietary/medication management plan before and during pregnancy?”