Diagnosis of a rare fetal haemoglobinopathy in the age of next-generation sequencing.
Neonatal cyanosis resulting from a fetal methaemoglobin variant is rare. Most such variants are only described in a few published case reports. We present the case of a newborn with unexplained persistent cyanosis, ultimately determined to have a γ-chain mutation causing Hb FM-Fort Ripley. This neonatal haemoglobinopathy can be challenging to diagnose, as significant oxygen desaturation may result from barely detectable levels of the mutant haemoglobin and co-oximetry studies may show a falsely normal methaemoglobin level. Our analysis of the infant's haemoglobin included high-performance liquid chromatography, cellulose acetate electrophoresis and citrate agar electrophoresis, which showed trace amounts of a suspected variant. Ultimately, the diagnosis was made through a novel application of next-generation sequencing (NGS). NGS-based diagnostic approaches are becoming increasingly available to clinicians, and our case provides a framework and evidence for the utilisation of such testing paradigms in the diagnosis of a rare cause of neonatal cyanosis.
Department of Pediatrics, New York University Langone Medical Center, New York, New York, USA Department of Pediatrics, Columbia University, New York, New York, USA.
Thomas A
TA
Hooven
Department of Pediatrics, Columbia University, New York, New York, USA.
Ellen M
EM
Hooper
Department of Pathology, Columbia University, New York, New York, USA.
Sandeep N
SN
Wontakal
Department of Pathology, Columbia University, New York, New York, USA.
Richard O
RO
Francis
Department of Pediatrics, Columbia University, New York, New York, USA.
Rakesh
R
Sahni
Department of Pediatrics, Columbia University, New York, New York, USA.
Margaret T
MT
Lee
D003490:Cyanosis / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D005319:Fetal Hemoglobin / Q000235:genetics; D006449:Hemoglobin M / Q000235:genetics; D006453:Hemoglobinopathies / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000235:genetics*; D008706:Methemoglobin / Q000235:genetics; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods*
D008706:Methemoglobin; D005319:Fetal Hemoglobin; D006449:Hemoglobin M; C059479:hemoglobin FM Fort Ripley