Fetal Cranial Biometric Abnormalities: The Value of Routine Ultrasound for Early Diagnosis of Glutaric Acidemia Type...

Glutaric acidemia type 1 (GA-1) is a severe, life-threatening organic acidemia. This study aimed to evaluate fetal ultrasound findings as early clues for GA-1.

A GA-1 case identified via newborn screening in Beijing and confirmed by exome sequencing was analyzed. His prenatal ultrasound records were retrospectively reviewed. A scoping review was performed following PRISMA-ScR guidelines to identify fetal GA-1 cases with prenatal imaging data from PubMed, Embase, and Scopus. Findings were summarized using the terminology reported in the original publications.

In the present case, both biparietal diameter (BPD) and head circumference (HC) exceeded the 97th percentile by 32 + 1 week of gestation. At 36 + 1 week, BPD remained above the 97th percentile, while HC was near it. Genetic analysis revealed two novel heterozygous GCDH variants: c.492C > G and c.648G > A. The scoping review identified six fetal GA-1 cases. Reported prenatal abnormalities included macrocephaly (5/6), enlarged Sylvian fissures (3/6), temporal lobe hypoplasia (2/6), cerebrospinal fluid (CSF) widening in the temporal fossa (1/6), and subependymal cysts (2/6).

Specific prenatal cranial findings, particularly fetal macrocephaly, may serve as early clues for GA-1. The diagnostic indication is strengthened when macrocephaly coexists with features such as Sylvian fissure widening. Recognition of these features could facilitate earlier identification and diagnosis of GA-1.