Cobalamin deficiency resulting in a rare haematological disorder: a case report

Solomon evaluated patients for cobalamin deficiency using the standard metabolic markers MMA and Hcys in a retrospective study of the records of patients in an ambulatory setting over a 10-year period [12]. The levels of the three metabolic markers were measured before any treatment was gi ven. Cobalamin, MMA, Hcys levels showed a wide variability over time, and taken individually or in combination did not predict or rule out a haematological or neurological response to cobalamin therapy [12].

There are also new methods available to diagnose cobalamin deficiency. In plasma, total plasma cobalamin is bound to two proteins, haptocorrin and transcobalamin. Normally, 80% of cobalamin is on plasma haptocorrin and forms a holohaptocorrin. About 20% of cobalamin is combined with transcobalamin II to form the biologically active fraction holotranscobalamin II (holoTC), which is available for cell use. HoloTC levels seem to be an early indicator of cobalamin deficiency [13]. Several studies showed that holoTC might be a promising first-line test or used in combination with a metabolic marker (MMA or Hcys) for diagnosing cobalamin deficiency [2,13]. In patients at risk or with clinical symptoms, we suggest a comprehensive care approach (Figur e 3) [2, 4].

Anti-intrinsic factors are more specific than antiparietal cell antibodies and are found in the serum of almost 40% of patients [14]. Both factors were positive in our patient. A gastric biopsy showed a marked lymphocyte infiltrate in the lamina propria, and the mucosa revealed intestinal metaplasia with goblet cells (Figure 2). The standard treatment of cobalamin deficiency is intramuscular, but oral supplementation has shown an efficacy equal to injection for pernicious anaemia and other cobalamin deficiencies [15]. Life-long cobalamin substitution is necessary in pernicious anaemia [4].

Conclusion
We present an unusual case of cobalamin deficiency resulting in severe pancytopaenia with thrombotic microangiopathy that was completely reversible after cobalamin substitution. Primary care physicians must be aware of patients at risk for cobalamin deficiencies irrespective of the ethnic origin of th patient. No single algorithm fits every patient, and there is no clear consensus on how to diagnose and treat cobalamin deficiency. Consequently, the diagnosis should rely on clinical epidemiology, clinical symptoms and biochemical markers.