What dietary restrictions are recommended for a patient with alkaptonuria?

Dietary Restrictions for Alkaptonuria

Protein restriction is NOT recommended for patients with alkaptonuria unless they are being treated with nitisinone, in which case moderate protein restriction (targeting tyrosine <700 μmol/L) is necessary to manage drug-induced tyrosinemia. 1, 2

Historical Context and Current Evidence

The outdated practice of protein restriction in alkaptonuria has been discredited in the literature and should be abandoned in untreated patients 1:

• 50% of alkaptonuria patients have historically followed some level of protein restriction at some point in their lives, contributing to clinical undernutrition 1
• No statistical evidence supports dietary protein manipulation to impede disease progression when measured against the validated AKUSSI severity score 1
• Alkaptonuria patients meet ESPEN criteria as "clinically undernourished" with significantly lower mid-upper arm circumference, grip strength, BMI, total energy and protein intake compared to population norms 1

Protein Management Based on Treatment Status

For Patients NOT on Nitisinone:

Maintain normal protein intake without restriction 1:

• Avoid protein restriction entirely, as it contributes to protein depletion without clinical benefit 1
• Ensure adequate energy intake to prevent the protein-energy wasting commonly seen in this population 1
• Monitor nutritional status given the high risk of malnutrition from limited mobility, frequent surgeries for joint replacements, and disease progression 1

For Patients on Nitisinone Treatment:

Implement tyrosine and phenylalanine dietary restriction when plasma tyrosine exceeds 700 μmol/L 2, 3:

• Nitisinone blocks homogentisic acid formation but causes elevated tyrosine levels (average 760 ± 181 μmol/L) that can lead to keratopathy 3
• Restrict both tyrosine AND phenylalanine together—phenylalanine restriction alone is ineffective at reducing tyrosine levels 2
• Protein restriction to approximately 40 g/day significantly reduces plasma tyrosine (from 755 ± 167 to 603 ± 114 μmol/L) 3
• Consider tyrosine/phenylalanine-free amino acid supplements to maintain adequate total protein intake while controlling tyrosine levels 2
• In observational studies, 4 out of 10 patients achieved target tyrosine <700 μmol/L with dietary protein restriction alone or combined with amino acid supplementation 2

Additional Dietary Considerations

Vitamin C, antioxidants, and micronutrients:

• A diet low in vitamin C, antioxidants, tyrosine, and phenylalanine may theoretically delay AKU progression, though long-term consequences remain unknown 4
• No statistical association exists between vitamin C supplementation (even at high doses) and disease severity as measured by AKUSSI score 1
• Similarly, selenium and zinc intake show no correlation with disease progression 1

Critical Pitfalls to Avoid

Do not implement blanket protein restriction in alkaptonuria patients 1:

• Historical protein restriction recommendations were poorly evidenced and contribute to the "perfect storm" of protein depletion risk factors 1
• Patients already face compromised nutritional status from limited mobility, frequent major surgeries, and high metabolic demands 1
• Only restrict protein in nitisinone-treated patients with elevated tyrosine levels 2, 3

Monitor for malnutrition indicators 1:

• Assess mid-upper arm circumference, grip strength, BMI, and body composition regularly 1
• Track total energy and protein intake through food diaries 1
• Measure serum albumin, total protein, and 24-hour urinary nitrogen 1

For nitisinone-treated patients, ensure ophthalmologic monitoring 3:

• Weekly eye examinations during treatment initiation to detect corneal toxicity from hypertyrosinemia 3
• Maintain tyrosine <700 μmol/L through combined tyrosine/phenylalanine restriction 2