[Elevated C5-OH Acylcarnitine]
β – Ketothiolase Deficiency (BKT)
Differential Diagnosis: Most likely 3-methylcrotonyl-CoA Carboxylase (3MCC) deficiency (infant or mother); may be 3-hydroxy-3-methylglutaryl (HMG)-CoA lyase deficiency; β-Ketothiolase deficiency; multiple Carboxylase deficiency (MCD) including biotinidase deficiency and holocarboxylase deficiency, 2-methyl-3-hydroxybutyric acidemia (2M3HBA), 3-methylglutaconic Aciduria (3MGA).
Condition Description: Each of the disorders is caused by a deficiency of the relevant enzyme. The substrate for which the enzyme is names, in most of the disorders, accumulates as does its potentially toxic metabolites.
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)
- Consult with pediatric metabolic specialist
- Evaluate the newborn (hypoglycemia, ketonuria, metabolic acidosis). If any of these parameters are abnormal or the 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 metabolic acidosis (poor feeding, lethargy, vomiting)
- Report findings to state newborn screening program (Carleigh Soule at 307-777-6297)
Diagnostic Evaluation: Confirmatory tests include urine organic acids on infant and mother, plasma acylcarnitine analysis, and serum biotinidase assay. The organic acids analysis on infant and mother should clarify the differential except for holocarboxylase deficiency and biotinidase deficiency (the latter clarified by biotinidase assay).
Clinical Considerations: The neonate is usually asymptomatic in 3MCC deficiency. However, episodic hypoglycemia, lethargy, hypotonia, and mild developmental delay can occur at any time from the neonatal period through childhood for any of these disorders. There is beneficial treatment that is specialized to each condition.
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 Star G - HRSA
For Algorithm: http://www.acmg.net/resources/policies/ACT/Visio-C5-OH(4-29-06).pdf