Transcobalamin II deficiency at birth

Area of Science:

• Genetics
• Biochemistry
• Pediatrics

Background:

• Transcobalamin II deficiency (TCN2 deficiency) is a rare, autosomal recessive disorder affecting cobalamin (vitamin B12) transport.
• This deficiency leads to intracellular cobalamin depletion, impairing key enzymes like methionine synthetase and methylmalonyl-CoA mutase.
• Untreated TCN2 deficiency can result in severe, long-term neurological sequelae.

Observation:

• This study reports on two sisters with a complete absence of functional Transcobalamin II.
• Both sisters were homozygous for a novel mutation (c.insC110) in the TCN2 gene, resulting in a non-functional protein.
• The older sister presented with pancytopenia and protein-losing enteropathy, while the younger sister was diagnosed pre-symptomatically.

Findings:

• Prompt administration of hydroxocobalamin led to rapid clinical recovery in the older sister.
• The younger sister, treated prophylactically after birth, showed increased urinary methylmalonic acid excretion in early life.
• Elevated methylmalonic acid suggests functional cobalamin deficiency may be present in fetal life, despite a lack of clinical manifestation.

Implications:

• Early diagnosis and prompt treatment with hydroxocobalamin are critical for preventing severe clinical manifestations and neurological damage in TCN2 deficiency.
• The findings suggest that cobalamin deficiency can impact fetal development, necessitating further investigation into prenatal screening and intervention.
• This case highlights the importance of genetic testing and timely therapeutic intervention for rare metabolic disorders.