A girl, born to healthy nonconsanguineous parents, was seen at age 3
months with pallor, lethargy, failure to thrive, and hypotonia. At age 7 months,
she was seen by a physician because of pallor, purpura, hypotonia, myoclonia,
epileptiform episodes of blinking, and chronic upper respiratory infections.
Her blood cell count revealed severe pancytopenia. Serum Cbl levels were in
the low to normal range. Methylmalonyl aciduria and homocystinuria were detected.
The total unsaturated Cbl binding capacity of serum, measured as previously
described,2 was 48 pmol/L (reference range,
440-880 pmol/L), without binding of [57Co]Cbl to TCII. Immunoreactive
TCII serum levels were 95 pmol/L (reference, >370 pmol/L). Culture findings
from the patient's fibroblasts incubated with 35S-methionine expressed
immunoreactive radio-labeled TCII with the same molecular weight as native
TCII, but no Cbl-binding TCII was secreted into the culture medium. The patient
was treated with intramuscular cyanocobalamin, 1000 µg every 10 days
for 1 year, and subsequently with oral cyanocobalamin (1000 µg per day)
and oral folic acid until age 16 years.