Renal thrombotic microangiopathy and pulmonary arterial hypertension in a patient with late-onset cobalamin C deficiency

Abstract

Cobalamin C (cblC) deficiency is the most commonly inherited inborn error of vitamin B12 metabolism. It is characterized by multisystem involvement with severe neurological, hematological, renal and cardiopulmonary manifestations. Disease is most commonly diagnosed early in the first decade of life. We report a case of a 20-year-old woman who developed severe pulmonary arterial hypertension while under nephrologic follow-up for chronic kidney disease. She had initially presented at 14 years of age with visual disturbance and acute renal failure and been diagnosed with thrombotic thrombocytopenic purpura on the basis of kidney biopsy findings of thrombotic microangiopathy and compatible ADAMTS13 (a disentegrin and metalloproteinase with a thrombospondin type 1 motif member 13). When cblC deficiency was eventually diagnosed, remarkable improvement in cardiopulmonary function was evident upon initiation of treatment. This case highlights the importance of a timely diagnosis and initiation of treatment for cblC deficiency. Clinical diagnosis may be challenged by asynchronous organ symptom presentation and by misleading laboratory tests, in this case: an initial low ADAMTS13. A simple test of plasma homocysteine level should be encouraged in cases of thrombotic microangiopathy and/or pulmonary artery hypertension.

Keywords: ADAMTS13 activity; cobalamin C deficiency; end-stage renal disease; pulmonary arterial hypertension; renal thrombotic microangiopathy.

Fig. 1.

Renal biopsy: this specimen consists of one core of renal cortex and medulla containing up to 24 glomeruli, 3 of which are globally sclerosed. Several glomeruli are ischemically shrunken with wrinkled capillary walls. There is mild-to-moderate (25%) interstitial fibrosis and tubular atrophy. Several arterioles and arteries show mural fibrinoid change with focal mucoid intimal thickening and fibrin/platelet thrombi.

Fig. 2.

1. TTE 2015: (1A) parasternal long axis showing moderate pericardial effusion, (1B) parasternal short axis showing D-shaped septum in diastole, (1C) apical view showing massive RV, (1D) Tricuspid regurgitation, (1E) Pulmonary regurgitation 2. TTE 2017: (2A) parasternal long axis normal, (2B) normal in short axis, (2C) apical view normal.