What is the cause and treatment of a fishy odor in a 6-month-old infant?

Fishy Odor in a 6-Month-Old Infant

Primary Differential Diagnosis

The most likely cause of a fishy odor in a 6-month-old infant is either trimethylaminuria (fish odor syndrome) or, less commonly, Aerococcus urinae urinary colonization, though bacterial vaginosis should be considered in the context of genital examination in older children. 1, 2, 3

Clinical Evaluation

History Taking

• Onset timing: Determine if the odor began after introduction of specific foods, particularly fish, eggs, or other choline-rich foods, as trimethylaminuria typically becomes apparent when dietary choline or trimethylamine N-oxide sources are introduced 4
• Dietary history: Document recent introduction of solid foods, especially marine fish, eggs, liver, legumes, and soy products which are high in choline 2, 4
• Odor characteristics: A rotting fish smell from breath, urine, sweat, and other bodily secretions suggests trimethylaminuria 1, 2, 5
• Pattern: Note if odor resolves with dietary elimination and recurs with reintroduction of specific foods 1
• Urinary symptoms: Assess for dysuria, frequency, or other urinary tract symptoms that might suggest A. urinae colonization 3

Physical Examination

• Growth parameters: Verify normal weight, length, and head circumference plotted on growth charts 6, 7
• Neurodevelopmental assessment: Confirm age-appropriate developmental milestones, as trimethylaminuria does not affect growth or development 1
• Skin examination: Assess for rashes, lesions, or signs of poor hygiene 6
• Genital examination: Inspect external genitalia for abnormalities, though bacterial vaginosis (which causes fishy odor) is primarily seen in adolescents, not infants 8, 6

Diagnostic Approach

Initial Testing

• Urinalysis and urine culture: Obtain to exclude urinary tract infection and identify A. urinae if present, noting that routine cultures may miss this organism in polymicrobial specimens 8, 3
• MALDI-TOF mass spectrometry: If available, this provides rapid identification of A. urinae, which can cause malodorous urine in otherwise healthy children 3
• Urine TMA/TMAO ratio: Measure under basal conditions; an elevated ratio suggests trimethylaminuria 4

Confirmatory Testing for Trimethylaminuria

• Marine fish meal challenge: This is the simplest and most acceptable diagnostic test in children—administer a meal containing marine (saltwater) fish and collect urine for TMA/TMAO measurement, with effects clearing more quickly than choline loading 4
• Choline loading test: Oral choline bitartrate loading allows estimation of residual oxidative capacity and is useful as an adjunct to molecular studies, though less practical in infants 4
• FMO3 genetic testing: Identify mutations in the FMO3 gene; homozygous or compound heterozygous mutations confirm diagnosis, though heterozygous variants may cause transient symptoms in early childhood due to enzymatic immaturity 1, 4

Important Diagnostic Pitfall

Do not initiate costly metabolic investigations before excluding A. urinae colonization, as this is easily treated and may be as frequent as trimethylaminuria in children with malodorous urine. 3

Management

For Trimethylaminuria

• Dietary modification: Restrict foods high in choline and carnitine including marine fish, eggs, liver, kidney, peas, soybeans, and certain legumes 2, 4
• Gradual reintroduction: After initial restriction, gradually reintroduce foods as tolerated, monitoring for odor recurrence; many children with transient forms can eventually consume normal portions without symptoms 1, 4
• Hygiene measures: Implement frequent bathing and clothing changes to minimize social impact 1
• Antibiotic suppression (if needed): Consider short courses of neomycin (most effective), metronidazole, or amoxicillin to reduce gut bacterial production of TMA, though effect is limited 2, 4
• Lactulose: May help suppress gut microflora production of trimethylamine 2

For A. urinae Colonization

• Antibiotic treatment: Simple antibiotic therapy effectively treats A. urinae infection and resolves the malodor 3
• Follow-up culture: Confirm eradication after treatment 3

Prognosis and Counseling

• Transient forms: Many cases in infants represent transient trimethylaminuria due to FMO3 enzymatic immaturity combined with heterozygous genetic variants, with resolution as the child matures 1, 4
• Persistent forms: Patients homozygous for common mutations (e.g., P153L) show virtually complete lack of oxidative capacity and require lifelong dietary management 4
• Psychosocial support: Recognize that this condition can be destructive to personal, social, and work life; provide appropriate counseling and support 5
• Quality of life: Dietary adjustments and hygiene measures effectively alleviate symptoms and improve quality of life in most cases 1, 2