Prolidase deficiency in an infant with an incidental finding of methaemoglobinaemia

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Prolidase deficiency is a rare autosomal recessive disorder.
• It is caused by pathogenic variants in the Peptidase D (PEPD) gene.
• Clinical manifestations can be severe and include gastrointestinal problems, skin lesions, and metabolic disturbances.

Observation:

• A 4-week-old infant presented with diarrhea and vomiting, initially misdiagnosed as cow's milk allergy.
• The infant's condition worsened, leading to metabolic acidosis and methaemoglobinaemia.
• Rapid trio exome sequencing was performed due to the deteriorating clinical state.

Findings:

• A homozygous pathogenic variant (c.978G>A, p.(Trp326*)) in the Peptidase D (PEPD) gene was identified.
• This genetic finding confirmed the diagnosis of prolidase deficiency.
• The identified variant is novel and has not been previously reported.

Implications:

• This case highlights the importance of considering rare genetic disorders in infants with unexplained severe symptoms.
• Early diagnosis of prolidase deficiency through genetic testing can facilitate timely management and improve patient outcomes.
• Further research into the genotype-phenotype correlations of PEPD variants is warranted.