Clinical, biochemical presentation and long term follow up of 11 patients of Cobalamin C deficiency

Introduction- Cobalamin C deficiency is a rare autosomal recessive but most common among inborn error of cobalamin metabolism disorders. Objectives- This retrospective single center study evaluates presenting clinical and biochemical features of 11 patients and their long term follow up after starting treatment. Methods- 11 patients were recruited. Diagnosis was based on either i) increased serum homocysteine, low methionine with urine positive for methylmalonic acid not attributable to nutritional B12 deficiency and/or ii) genetic testing (6 patients). Results- 7/11 (63%) presented before 1 year of age. Most common presentation was development delay (82%) followed by seizures (73%). Hypotonia and Alopecia (55%) were frequent findings. Median homocysteine on presentation was 137.59 micromoles/L (< 10), 82% patients had high MCV- median 97.9 fL (76-90 fL). MRI Brain was abnormal in 45% patients. All patients were started on hydroxy-cobalamin (injectable +/- oral), pyridoxine, folic acid and betaine. 1 patient succumbed to disease. On follow up, 5 out of 8 patients became seizure free & off ASDs. 9 out of 10 had independent ambulation. 6 out of 10 had cognitive deficits. Median homocysteine level on follow up was 140.9 micromoles/L while median MCV was 88.2 fL. All 6 patients who were diagnosed and/or confirmed by genetic testing, had common pathogenic mutation c.394C>T (R 132*) in exon 3 of MMACHC gene-described in Indian literature. Conclusion- There is significant improvement in motor development (independent ambulation, ADLs) and seizure control on appropriate treatment. However, most patients continue to have cognitive deficits despite of treatment.
Keywords: Cobalamin C deficiency, MMACHC gene, homocysteine, methyl malonic acid