To describe a series of patients with CblC with varying ages of symptom onset, diagnosis, and initiation of treatment, highlighting the importance of the expanded NBS in the early diagnosis and treatment of children with CblC.

CblC is caused by a mutation in the MMACHC gene, characterized by elevated plasma homocysteine and methylmalonic acid with low plasma methionine. Early onset form of CblC typically presents in the first year of life with feeding difficulties, metabolic acidosis, altered mental status, and hypotonia.  The late onset form classically presents after 4 years of life with neurocognitive decline, psychiatric symptoms, and abnormal neurological exam.  Treatment consists of administering high doses of hydroxycobalamin which gradually lowers levels of homocysteine and methylmalonic acid. Early identification and treatment of individuals with CblC is important in preventing long term morbidity.  Expanded NBS has become invaluable in early identification of rare metabolic disorders, including CblC, and has facilitated identification and treatment of affected individuals. Early identification of affected patients has also allowed expanded genetic testing for family members and led to treatment initiation of presymptomatic affected family members born before expanded NBS. 

We present a case series of three individuals with CblC with variable age of presentation, symptoms, and time to diagnosis. Two patients were born prior to the expansion of the NBS and had delays in diagnosis. One patient was diagnosed via the NBS and started treatment in infancy. Diagnosis of CblC in our patient cohort has additionally led to testing and early presymptomatic treatment of affected family members.

Expanded NBS plays an important role in decreasing time to diagnosis and initiation of treatment of individuals affected by CblC, as well as identifying older affected family members prior to symptom onset.