[Elevated C3 Acylcarnitine]
Methylmalonic Acidemia – Mutase Deficiency (MUT)
Differential Diagnosis: Proprionic Acidemia (PA); Methylmalonic Acidemias (MMA), including defects in B12 synthesis and transport; maternal severe B12 deficiency.
Condition Description: PA is caused by a defect in propionyl-CoA Carboxylase which converts propionyl-CoA to methylmalonyl-CoA; MMA results from a defect in methylmalonyl-CoA mutase which converts methylmalonyl-CoA to succinyl-CoA or from lack of required B12.cofactor for methylmalony-CoA mutase (cobalamin A, B, C, D, and F).
MEDICAL EMERGENCY - TAKE THE FOLLOWING IMMEDIATE ACTIONS:
- Contact family to inform them of the newborn screening result and ascertain clinical status (poor feeding, vomiting, lethargy, tachypnea)
- Consult with pediatric metabolic specialist
- Evaluate the newborn; check urine for ketones and, if elevated or infant is ill, initiate emergency treatment as indicated by metabolic specialist and transport IMMEDIATELY to tertiary center with metabolic specialist
- Initiate confirmatory/diagnostic testing as recommended by specialist
- Educate family about signs, symptoms and need for urgent treatment of hyperammonemia and metabolic acidosis (poor feeding, lethargy, vomiting, tachypnea)
- Report findings to state newborn screening program (Carleigh Soule at 307-777-6297)
Diagnostic Evaluation: Plasma acylcarnitine confirms the increased C3. Blood amino acid analysis may show increased glycine. Urine organic acid analysis will demonstrate increased metabolites characteristics of Propionic Acidemia or increased Methylmalonic acid characteristic of Methylmalonic Acidemia. Plasma total homocysteine will be elevated in the cobalamin C, D and F deficiencies. Serum vitamin B12 may be elevated in the cobalamin disorders.
Clinical Considerations: Patients with PA and severe cases of MMA typically present in the neonate with metabolic ketoacidosis, dehydration, hyperammonemia, ketonuria, vomiting, hypoglycemia, and failure to thrive. Long-term complications are common, early treatment may be lifesaving and continued treatment may be beneficial.
Additional Information: (Click on the name to take you to the website)
Genetic Home Reference Wyoming Department of Health
Gene Tests Colorado Newborn Screening
New England Consortium American Academy of Pediatrics
For Algorithm: http://www.acmg.net/resources/policies/ACT/Visio-C3(4-29-06).pdf