Hypocitrullinemia in expanded newborn screening by LC-MS/MS is not a reliable marker for ornithine transcarbamylase deficiency.
In an expanded newborn screening program for inborn errors of metabolism by LC-MS/MS in Tuscany, six newborns out of 169,000 showed decreased blood citrulline levels. In one of them, molecular analysis of the OTC gene identified the known p.Trp265Leu mutation, which is correlated with late-onset ornithine transcarbamylase deficiency (OTCD). Hypocitrullinemia is not a reliable marker for OTCD newborn screening, especially for late-onset forms that may exhibit normal citrulline levels. However, when hypocitrullinemia is detected in a newborn in whom intestinal dysfunction and prematurity have been excluded, OTCD should be investigated first because of the OTCD incidence (1:14,000) and the small size of the OTC gene coding sequence.
Cavicchi
C
C
Metabolic and Muscular Unit, Clinic of Pediatric Neurology, AOU Meyer, Florence, Italy.
Malvagia
S
S
la Marca
G
G
Gasperini
S
S
Donati
M A
MA
Zammarchi
E
E
Guerrini
R
R
Morrone
A
A
Pasquini
E
E
D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods*; D002956:Citrulline / Q000097:blood; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007558:Italy / Q000453:epidemiology; D008297:Male; D015997:Neonatal Screening / Q000379:methods*; D009954:Ornithine Carbamoyltransferase / Q000235:genetics*; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000235:genetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D015415:Biomarkers; D002956:Citrulline; D009954:Ornithine Carbamoyltransferase