Thrombotic microangiopathy and breastfeeding: where is the link? Answers

The thrombotic microangiopathy was caused by a cobalamin defect (deficiency or due to a metabolic disorder). Neonatal thrombotic microangiopathy can be explained by a severe deficiency (<10%) in ADAMTS13, a plasma metalloprotease (also known as von Willebrand factor-cleaving protease), either due to congenital absence of the functional protein or to the presence of acquired anti-ADAMTS13 antibodies; however, this diagnosis was excluded by normal ADAMTS13 activity. There were no biological or clinical parameters in favor of a thrombotic microangiopathy caused by Shiga toxin-producing Escherichia coli infection and other specific infectious agents, such as Streptococcus pneumonia. The favorable evolution within 12 h, without terminal complement blockade treatment, does not support a diagnosis of atypical hemolytic uremic syndrome. Conversely, all the signs for a vitamin B12 defect are present: megaloblastic anemia, neutropenia, and a markedly elevated urinary methylmalonic acid level. The vitamin B12 level was very high and plasma homocysteine level was very low, but this investigations were made after plasma infusion and after treatment with parenteral vitamin B12.

The absorption, transport, storage, and intracellular processing of cobalamin are complex. Vitamin B12 neonatal disorder is linked either to a cobalamin deficiency due to insufficient oral intake or to inborn errors of vitamin B12 metabolism. In our case, 5 days after the beginning of treatment with parenteral vitamin B12, the urinary methylmalonic acid levels were already low (2 μmol/mmol) and the thrombotic microangiopathy had been stopped. Vitamin B12 parenteral treatment would not be able to overcome the metabolic block in inborn errors of vitamin B12 metabolism in such a fast and complete manner. Thus, the thrombotic microangiopathy in our patient was likely due to a vitamin B12 deficiency.

This patient was exclusively breastfed. Therefore, the mother has to be investigated. The mother also had a severe vitamin B12 deficiency (< 50 pmol/L) with a high level of homocysteine and an elevated urinary methylmalonic acid level, which confirmed our diagnosis of vitamin B12 deficiency caused by inadequate oral intake of vitamin B12.