Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: a 16-year experience.
Despite implementation of newborn screening (NBS), outcomes in cobalamin C disease (cblC) remain poor. Therapy with hydroxycobalamin and betaine is widely used, but dietary recommendations vary among metabolic centers. We present a longitudinal analysis of the relationship between metabolic control, diet, and outcomes in a cohort of cblC patients.



We completed a retrospective analysis of 12 patients with cblC referred for abnormal NBS results and followed in our center between 1999 and 2015.



Of the patients, 87.5% had intellectual disability and 75% had retinopathy; 16.7% had one episode of mild acidosis. However, no patients manifested major metabolic decompensation. Developmental outcomes correlated more closely with initial metabolic abnormalities than with long-term metabolic control. Increased intake of medical foods resulted in better control but also perturbations in the ratios of essential amino acids and lower z-scores for head circumference. We found no relationship between diet and cognitive outcomes.



Although dietary therapy for cblC patients improves metabolic control, few patients experience metabolic decompensation regardless of diet. Increased incomplete protein intake is not correlated with improvements in outcomes. Overall, outcomes are poor despite early initiation of therapy and regardless of the dietary strategy used.Genet Med advance online publication 02 February 2017.
Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Rebecca C
RC
Ahrens-Nicklas
Department of Child and Adolescent Psychiatry and Behavioral Sciences, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ashley M
0000-0002-4362-6295
AM
Whitaker
Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Paige
P
Kaplan
Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sanmati
0000-0002-3387-5968
S
Cuddapah
Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jessica
0000-0002-7492-3444
J
Burfield
Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jennifer
J
Blair
Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ligia
0000-0002-1007-3364
L
Brochi
Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Marc
M
Yudkoff
Division of Human Genetics, The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Can
C
Ficicioglu
D015331:Cohort Studies; D004044:Dietary Proteins / Q000494:pharmacology; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D008715:Methionine / Q000097:blood; D008764:Methylmalonic Acid / Q000097:blood; D015997:Neonatal Screening; D019965:Neurocognitive Disorders / Q000178:diet therapy / Q000517:prevention & control; D012189:Retrospective Studies; D055502:Secondary Prevention; D014806:Vitamin B 12 Deficiency / Q000178:diet therapy* / Q000503:physiopathology / Q000517:prevention & control
D004044:Dietary Proteins; D006710:Homocysteine; D008764:Methylmalonic Acid; D008715:Methionine