2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Fetal Asparagine Synthetase Deficiency Diagnosed by Carrier Screening in the Workup of Fetal Growth Restriction

Pdf Summary

Fetal Asparagine Synthetase Deficiency (ASD) is a rare autosomal recessive disorder that affects the metabolic conversion of aspartic acid to asparagine. This conversion is crucial for brain development, as asparagine is poorly transported across the blood brain barrier. Clinical manifestations of ASD include microcephaly, hypotonia, developmental delays, apnea, and seizures. While approximately 60 cases of ASD have been reported in the literature, most describe postnatal features and little is known about the prenatal phenotype.<br /><br />This case report presents a case of fetal presentation of ASD that was diagnosed through genetic carrier screening as part of the workup for fetal growth restriction (FGR). A 28-year-old Salvadoran woman, with a history of two previous uncomplicated pregnancies, presented for a routine anatomy ultrasound at 21 weeks of gestation. Both she and her partner tested negative for carrier status through genetic screening. However, prenatal evaluations revealed early-onset FGR, microcephaly, and cerebellar hypoplasia in the fetus.<br /><br />Further genetic testing confirmed the diagnosis of ASD, with the presence of homozygous ASNS c.277C>T, p.(Q93*). Postnatal magnetic resonance imaging (MRI) showed microcephaly, diminished cerebral and cerebellar volume, and delayed myelination. The infant experienced severe developmental delay and spastic quadriplegia, ultimately leading to cardiac arrest and death at 5 months of age.<br /><br />This case highlights the challenges of counseling and prognostication in the prenatal diagnosis of rare genetic disorders. It also demonstrates how genetic carrier screening can assist in the diagnostic workup of non-specific or genetically heterogeneous sonographic abnormalities. While this case provides insight into the natural history of the prenatal presentation of ASD, further cases are needed to fully understand the prenatal phenotype.

Asset Subtitle

Presenting Author - Bobby Brar, MD; Co-Author - Michael Leeson, MD; Co-Author - Cathleen Lawson, MS; Co-Author - Gerald V. Raymond, MD, FACMG; Co-Author - Karin J. Blakemore, MD; Co-Author - Christine Hertenstein, MGC; Co-Author - Kristen (Leppert) Miller, MGC, CGC; Co-Author - Sabrina Southwick, MS; Co-Author - Carol Nowlen, MS, CGC; Co-Author - Angie Jelin, MD;

Meta Tag

Congenital Anomaly

Fetal Pathology

Fetal Therapy

Prenatal Diagnosis

Ultrasound

Co-Author Michael Leeson, MD

Co-Author Cathleen Lawson, MS

Co-Author Gerald V. Raymond, MD, FACMG

Co-Author Karin J. Blakemore, MD

Co-Author Christine Hertenstein, MGC

Co-Author Kristen (Leppert) Miller, MGC, CGC

Co-Author Sabrina Southwick, MS

Co-Author Carol Nowlen, MS, CGC

Co-Author Angie Jelin, MD

Presenting Author Bobby Brar, MD

Keywords

Fetal Asparagine Synthetase Deficiency

ASD

autosomal recessive disorder

aspartic acid

asparagine

brain development

microcephaly

hypotonia

developmental delays

genetic carrier screening