Rare case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia: A report

Characterized by proteinuria, hypoalbuminemia, and edema, nephrotic syndrome represents a heterogeneous alteration induced by several underlying diseases, including metabolic diseases. One of these extremely rare causes is represented by the cobalamin C defect, an autosomal recessive disorder due to mutations of the MMACHC gene, which impairs vitamin B12 metabolism. Although classically associated with hematological and neurological symptoms, renal involvement in cblC defect is increasingly recognized but still very rare.

A 7-month-old male patient presented with fatigue and edema. Initial laboratory investigations showed anemia, thrombocytopenia, hypoalbuminemia, and proteinuria. Peripheral blood smear indicated hemolysis. Soon after, his condition deteriorated and he was admitted to intensive care due to respiratory distress on account of pleural effusion, hypertensive crisis, and severe anemia. Laboratory findings including anemia, thrombocytopenia, hypoalbuminemia, proteinuria, and hemolysis peripheral blood smear revealed hemolysis. High total plasma homocysteine levels were 1700.5 micromol/L. There were low methionine levels about 2.85 micromol/L. Genetic confirmation of defect in cblC with biallelic MMACHC gene mutations. Treatment was started on hydroxycobalamin 1 mg/day intramuscularly, along with folic acid and betaine. In view of extreme elevation of homocysteine levels of 232,000 μmol/L, the doses of treatment were doubled. Nephrotic syndrome and pancytopenia gradually improved, respiratory distress regressed and blood pressure stabilised. The patient did well at the last follow up visit with decrease in homocysteine levels to 4.6 micromol/L, though methionine levels remained low.

This case highlights the necessity of recognizing metabolic disorders, including cblC defects, even in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive treatment that includes supplementation of vitamin B12 may prevent irreversible renal damage. Although cblC defect represents one of the common causes for atypical hemolytic uremic syndrome, it should be included in differential diagnoses of nephrotic syndrome, especially if combined with hemolysis. This case represents one of the highest homocysteine levels ever reported in the literature and should be considered for increasing awareness and facilitating early diagnosis of nephrotic syndrome related to a defect in cblC.

Reference:

Akar, H. T., Yıldız, H., Öztürk, Z., Karakaya, D., Sezer, A., & Olgaç, A. (2024). Case presentation: a severe case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia. BMC Nephrology, 25(1). https://doi.org/10.1186/s12882-024-03656-1