Essential fatty acid profiling for routine nutritional assessment unmasks adrenoleukodystrophy in an infant with isovaleric acidaemia.
We report a 16-month-old asymptomatic male with enzyme confirmed isovaleric acidaemia (IVA; isovaleryl-CoA dehydrogenase deficiency; OMIM 243500) who, upon routine nutritional follow-up, presented evidence of peroxisomal dysfunction. The newborn screen (2 days of life) revealed elevated C(5)-carnitine (2.95 μmol/L; cutoff <0.09 μmol/L) and IVA was subsequently confirmed by metabolic profiling and in vitro enzymology. Plasma essential fatty acid (EFA) analysis, assessed to evaluate nutritional status during protein restriction and L: -carnitine supplementation, revealed elevated C(26:0) (5.0 μmol/L; normal <1.3). Subsequently, metabolic profiling and molecular genetic analysis confirmed X-linked adrenoleukodystrophy (XALD). Identification of co-inherited XALD with IVA in this currently asymptomatic patient holds significant treatment ramifications for the proband prior to the onset of neurological sequelae, and critically important counselling implications for this family.
Bonilla Guerrero
R
R
Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Wolfe
L A
LA
Payne
N
N
Tortorelli
S
S
Matern
D
D
Rinaldo
P
P
Gavrilov
D
D
Melan
M
M
He
M
M
Steinberg
S J
SJ
Raymond
G V
GV
Vockley
J
J
Gibson
K M
KM
D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D004252:DNA Mutational Analysis; D005228:Fatty Acids, Essential / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D050769:Isovaleryl-CoA Dehydrogenase / Q000097:blood / Q000172:deficiency / Q000235:genetics; D008297:Male; D015997:Neonatal Screening; D015596:Nutrition Assessment; D018901:Peroxisomal Disorders / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D011237:Predictive Value of Tests
D015415:Biomarkers; D005228:Fatty Acids, Essential; D050769:Isovaleryl-CoA Dehydrogenase