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Hydroxocobalamin dose escalation improves metabolic control in cblC
Author(s) -
CarrilloCarrasco N.,
Sloan J.,
Valle D.,
Hamosh A.,
Venditti C. P.
Publication year - 2009
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-009-1257-y
Subject(s) - cobalamin , hydroxocobalamin , methylmalonic acid , homocystinuria , transsulfuration , homocysteine , medicine , methylmalonic acidemia , methylmalonic aciduria , endocrinology , vitamin b12 , methionine , gastroenterology , cyanocobalamin , biochemistry , biology , cystathionine beta synthase , amino acid
Summary Cobalamin C (cblC), a combined form of methylmalonic acidaemia and hyperhomocysteinaemia, is recognized as the most frequent inborn error of intracellular cobalamin metabolism. This condition can be detected by expanded newborn screening and can have an acute neonatal presentation that is life‐threatening if not suspected and promptly treated. Intramuscular (IM) hydroxocobalamin (OHCbl) is the main treatment for patients with cblC, but formal dosing guidelines do not exist. A clinical improvement and a decrease of plasma methylmalonic acid (MMA) and total homocysteine (tHcy) levels, and an increase in methionine are typically observed after its initiation. It is well recognized that despite treatment, long‐term complications such as developmental delay and progressive visual loss, may still develop. We describe the biochemical response of a 13‐year‐old boy with worsening metabolic parameters despite strict adherence to a conventional treatment regimen. We progressively increased the OHCbl dose from 1 to 20 mg IM per day and observed a dose‐dependent response with an 80% reduction of plasma MMA (25 to 5.14 μmol/L; normal range <0.27 μmol/L), a 55% reduction of tHcy (112 to 50 μmol/L; normal range: 0–13 μmol/L) and a greater than twofold increase in methionine (17 to 36 μmol/L; normal range: 7–47 μmol/L). This suggests that higher OHCbl doses might be required to achieve an optimal biochemical response in cblC patients, but it is unknown whether it may slow or eliminate other complications. Future clinical trials to determine the benefits of higher‐dose OHCbl therapy in patients with cblC and other disorders of intracellular cobalamin metabolism should be planned.