Deficiency of
ornithine-δ-
aminotransferase (OAT) in humans results in
gyrate atrophy. Early diagnosis may allow initiation of treatment before irreversible damage has occurred. However, diagnosis is commonly delayed well into adulthood because of the nonspecific character of initial symptoms. Here, we report findings in a neonate who was evaluated because of a positive family history of
OAT deficiency. The reversed enzymatic flux in early infancy resulted in borderline low
ornithine concentration - evoking
urea cycle disturbances - and increased
proline. In addition, plasma
citrulline was low. Consequently, the
proline/
citrulline ratio in plasma was increased compared to controls. To find out whether
amino acid profiling in neonatal dried blood spots is suitable to detect
OAT deficiency, we evaluated the original newborn dried blood spots of two affected patients and compared it with a database of >450,000 newborns tested in Minnesota since 2004.
Proline concentrations (777 and 1,381 μmol/L) were above the 99 percentile (776 μmol/L) of the general population, and
citrulline concentrations (4.5 and 4.9 μmol/L) only just above the 1 percentile (4.37 μmol/L). The
proline/
citrulline ratio was 172.9 and 281.8, respectively. This ratio was calculated retrospectively in the normal population, and the 99 percentile was 97.6. Applying this ratio for NBS could lead to early and specific detection of neonatal
OAT deficiency, with no additional expense to newborn screening laboratories quantifying
amino acids. Given that early diagnosis of OAT disease can lead to earlier treatment and prevent
visual impairment, further studies are indicated to evaluate whether newborn screening for
OAT deficiency is warranted.