Transcobalamin II Deficiency: Rare Differential Diagnosis in a Neonate with Hematological Disease and Failure to Thrive

Introduction: Vitamin B12 (cobalamin) is an essential nutrient. In case of a nutritional deficiency, impaired transport or compromised metabolism, DNA synthesis, or metabolism of methylmalonyl CoA and homocysteine can be compromised. Severe encephalopathy is a frequent clinical feature; biochemical hallmark is increased urinary methylmalonate excretion.

Case Summary: A three week old female neonate from Afghanistan presented with poor breast feeding, failure to thrive, diarrhea, restlessness and features resembling late-onset septicemia. She had reduced muscle tone and an extensive diaper rash. Pregnancy and birth were uneventful. She has four elder, healthy siblings. 20 years ago, the first child of her parents died of anemia in the fourth week of life. Due to pancytopenia, bone marrow aspirate and biopsy were performed and results suggestive of aplastic anemia, showing a severe reduction of all cell lines, no malignancy. Subsequent metabolic evaluations showed elevated plasma homocysteine (52.2 µmol/L) and urinary methylmalonic acid (1,184 µmol/mmol creatinine), but normal plasma methionine and serum vitamin B12 levels as a clue to compromised metabolism or transport of cobalamin. Under intravenous cobalamin supplementation homocysteine and methylmalonate levels normalized quickly. Molecular genetics confirmed a homozygous exon 7 deletion in the TCN II gene. With parenteral vitamin B12 treatment, the child clinically recovered and the blood count normalized.

Conclusion: A clinical presentation, suggestive of a hematological disorder turned out to be an inborn error of metabolism. A broad differential diagnosis is essential in pancytopenia with respect to treatment, prognosis and family planning.