Citrullinemia with an Atypical Presentation: Paroxysmal Hypoventilation Attacks

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Citrullinemia type 1 (CTLN1) is a rare inherited urea cycle disorder caused by argininosuccinate synthetase deficiency.
• Urea cycle disorders (UCDs) are often associated with hyperammonemia, but atypical presentations can occur.

Observation:

• An infant presented with acute loss of tonus and cyanotic hypoventilation attacks without elevated ammonia levels.
• Physical and neurological examinations were normal, but blood and urine citrulline levels were significantly increased.

Findings:

• Genetic analysis revealed a novel heterozygous mutation p.A94V (c.281C>T) and a known heterozygous mutation p.W179R (c.535C>T) in the ASS1 gene.
• This represents the first reported case of CTLN1 with this specific atypical clinical presentation and a new mutation.

Implications:

• Urea cycle disorders should be considered in the differential diagnosis of unexplained apnea or hypoventilation in infants, even without hyperammonemia.
• The identification of a novel ASS1 mutation expands the known genetic landscape of CTLN1.
• This case underscores the importance of considering rare metabolic disorders in neonates with seemingly non-specific neurological symptoms.