Table 7.

Recommended Surveillance for Individuals with Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome

System/ConcernEvaluationFrequency
Constitutional Measure HT, WT, & HC. BMI should always be included.
  • From time of diagnosis until adolescence
  • During pre-school years: follow WT, HT & HC in conjunction w/PCP even when not seen in metabolic clinic.
Metabolic status Concentration of:
  • Plasma ammonia & amino acids 1, 2
  • Urine amino acids, organic acids, & orotic acid
Phenylbutyrate & its metabolites (phenylacetate, phenylacetate-glutamine) to optimize management & check adherence		Routine monitoring based on:
  • Age:
    <1 yr: every mo
    1-2 yrs: every 2-3 mos
    >2 yrs: every 3-4 mos
  • History of adherence
  • History of metabolic decompensation
Mood, behavior,
eating 		Parents should be alert to subtle behavior changes which may suggest ↑ plasma concentrations of glutamine & ammonia.
  • Incl changes in eating habits, motor skills, & behavior
  • In children age ≤3 yrs, especially in flu season or hot/humid weather
Development Evaluation by developmental pediatrician to assess & manage emergence of behavior issues (ADD/ADHD)Prior to starting kindergarten; evaluate as needed.
Academic
performance 3 		Neurocognitive evaluation1x/yr if any academic regression or behavior changes occur
Neurologic
evaluation 		A detailed evaluation by neurologist especially in children w/neonatal, infantile, & early school-age onset to assess for slow, progressive neurologic involvementMonitor 1x/yr even when metabolic control is optimal, especially in children age <12 yrs.
Perform MRI/MRS in consultation w/neurologist.MRI/MRS every 2 yrs to correlate motor/cognitive/language development w/imaging findings (possible progressive cerebral atrophy, stroke-like lesions, &/or white matter disease)

ADD = attention-deficit disorder; ADHD = attention-deficit/hyperactivitry disorder; BMI = body mass index; HC = head circumference; HT = height; PCP = primary care provider; WT = weight

1.

Low plasma concentrations of essential amino acids (isoleucine, leucine, valine, and arginine) could trigger a catabolic state, requiring readjustment of diet/formulas and/or supplements.

2.

Low plasma concentrations of lysine may lead to delays in growth and development in infants.

3.

Poor school performance may lead to low self-esteem and/or behavioral problems that could influence adherence to a protein-restricted diet.

From: Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

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