13.2 Nutritional Management of Phenylketonuria (PKU)

Phenylketonuria (PKU) is a genetic disorder that messes with how the body processes phenylalanine. Without treatment, it can cause serious brain damage. But with early detection and proper management, people with PKU can lead normal lives.

The key to managing PKU is a super strict diet. It's all about limiting protein intake and using special medical foods. Regular blood tests help fine-tune the diet. New treatments like BH4 therapy are giving some patients more food options.

Phenylketonuria (PKU) Overview

Genetic Basis and Biochemical Implications

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• Phenylketonuria (PKU) results from a genetic mutation affecting phenylalanine metabolism
• Phenylalanine accumulates in the blood and tissues due to impaired conversion to tyrosine
• Phenylalanine hydroxylase enzyme deficiency causes inability to break down phenylalanine
• Buildup of phenylalanine leads to neurotoxicity and developmental issues
• Autosomal recessive inheritance pattern requires both parents to be carriers

Screening and Diagnosis

• Newborn screening detects PKU through blood spot test within 24-48 hours after birth
• Guthrie test measures phenylalanine levels in blood samples
• Positive screening results prompt confirmatory testing and genetic analysis
• Early diagnosis crucial for preventing cognitive impairment and other complications
• Follow-up testing includes regular monitoring of blood phenylalanine levels

Clinical Manifestations and Long-term Effects

• Untreated PKU can cause severe cognitive impairment and developmental delays
• Symptoms include seizures, behavioral problems, and microcephaly
• Fair skin and hair due to reduced melanin production (tyrosine deficiency)
• Musty odor in urine and sweat from phenylacetic acid accumulation
• Long-term effects include decreased executive function and psychiatric disorders

Dietary Management

Low-Protein Diet Principles

• Strict low-protein diet restricts natural protein intake to control phenylalanine levels
• Carefully calculated protein allowance based on individual tolerance and metabolic needs
• Avoidance of high-protein foods (meat, fish, eggs, dairy, nuts, and legumes)
• Emphasis on low-protein alternatives (fruits, vegetables, and specially manufactured low-protein products)
• Regular monitoring and adjustment of diet based on blood phenylalanine levels

Medical Foods and Supplementation

• Phenylalanine-free medical foods provide essential amino acids, vitamins, and minerals
• Specially formulated protein substitutes ensure adequate nutrition without phenylalanine
• Tyrosine supplementation necessary due to impaired conversion from phenylalanine
• Careful balance of nutrients to support growth and development
• Aspartame avoided in diet due to its phenylalanine content (found in diet sodas and sugar-free products)

Monitoring and Adherence

• Regular blood phenylalanine levels monitoring guides dietary management
• Target blood phenylalanine levels vary by age and individual factors
• Frequent adjustments to diet based on blood levels and growth patterns
• Challenges in adherence increase during adolescence and adulthood
• Importance of lifelong dietary management to prevent neurological damage

Advanced Treatments

Pharmacological Interventions

• Tetrahydrobiopterin (BH4) therapy enhances residual phenylalanine hydroxylase activity
• BH4 allows increased dietary protein tolerance in some PKU patients
• Large neutral amino acids (LNAA) supplementation competes with phenylalanine for brain uptake
• LNAA therapy may help reduce brain phenylalanine levels and improve neurocognitive outcomes
• Enzyme replacement therapy and gene therapy under investigation as potential future treatments

Special Considerations for Maternal PKU

• Maternal PKU syndrome risks severe fetal complications if untreated during pregnancy
• Strict metabolic control essential before conception and throughout pregnancy
• Increased calorie and protein needs during pregnancy require careful dietary planning
• Frequent monitoring of maternal blood phenylalanine levels (2-3 times per week)
• Potential use of BH4 therapy during pregnancy to help maintain metabolic control

Emerging Therapies and Future Directions

• Enzyme substitution therapy using phenylalanine ammonia lyase (PAL) shows promise
• Gene therapy approaches aim to introduce functional phenylalanine hydroxylase gene
• Hepatocyte transplantation being explored as a potential treatment option
• Research into gut microbiome manipulation to enhance phenylalanine metabolism
• Development of more palatable and nutritionally complete medical foods ongoing