MSACL 2019 EU Abstract

Maternal Glutaric Aciduria Type 1 (GA 1) Detected Through Newborn Screening in Croatia

Ivana Križić (1), Iva Bilandžija Kuš (1), Ana Škaričić (1), Ksenija Fumić (1), Tamara Žigman (2) Danijela Petković Ramadža (2) Ivo Barić (2)
(1) Department of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia (2) Department of Pediatrics, University Hospital Center Zagreb, Zagreb, Croatia

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Ivana Križić (Presenter) University Hospital Center Zagreb >> POSTER (PDF)

Relevant Financial Disclosures (within past 24 months) Honorarium/Expenses Shimadzu Conflict mitigation NOT REQUIRED.

INTRODUCTION: Glutaric aciduria type 1 (GA-1; OMIM#231670) is an autosomal recessive inborn error of metabolism caused by deficiency of glutaryl-CoA dehydrogenase (GCDH) located in the catabolic pathways of L-lysine, L-hydroxylysine, and L-tryptophan. The enzymatic defect gives rise to neurotoxic metabolite glutaric acid (GA) and 3- hydroxyglutaric acid
(3-OH-GA) in the urine, and to glutaryl carnitine (C5DC), the marker metabolite used for newborn screening (NBS) . As in most inborn errors of metabolism, the phenotypic spectrum of GA 1 is broad. Most untreated individuals with GA-1 experience acute encephalopathic crises during the first six years of life that are triggered by infectious diseases, febrile reaction to vaccinations, and surgery. However, a small group of untreated GA 1 patients remains asymptomatic, even in adult life. Treatment for GA-1 consists of a low lysine diet, carnitine, and high-energy intake during illness.
OBJECTIVES: We describe a woman with GA 1 in whom the diagnosis was unsuspected until a low free carnitine level was found in her twin infants during routine newborn screening.
METHODS: Samples for NBS were prepared using Recipe reagent kit ClinSpot ® Complete Kits, amino acids and acylcarnitines in dried blood spots (DBS) on a tandem mass spectrometer coupled with high performance liquid chromatography, LC-MS/MS (MS8050 coupled with UPLC Nexera, both Shimadzu). Samples were ionized using electrospray ionization (ESI) in positive ion mode. Concentrations of individual acylcarnitine and amino acid species were calculated using isotope-labelled internal standards of known concentration for each analyte.
Urine organic acids were analyzed on capillary gas chromatography coupled with mass spectrometry (GC-MS-QP2010Plus, Shimadzu).
RESULTS: Isolated carnitine deficiency was found in one of the twin infants. The free carnitine (C0) concentration at day 3 in the newborn screening was 6.2 µmol/L (cut-off >8.8). Confirmation tests included plasma and DBS acylcarnitine profile for infants and their mother. The maternal DBS acylcarnitine profile showed markedly elevated glutarylcarnitine (C5DC= 1.9 µmol/L, cut-off <0.35) and decreased C0 (C0=4.0, cut-off >10). All of the metabolic findings of the baby were normal except for very low free carnitine level. Additional metabolic testing for mother showed clear elevations of glutaric and 3-hydroxyglutaric acid in urine organic acid analysis. Neonatal parameters normalized during the following weeks and confirmatory work-up of the non-affected neonates is negative.
CONCLUSION: An asymptomatic woman with GA 1 was detected through her infant´s newborn screening. This case has confirmed that expanded NBS may, besides expected reduction in the number of deceased or affected children, also yield other useful results: It can detect certain diseases in a mother, some acquired diseases in newborns and diseases in siblings of ill children detected by screening.