Multiple Carboxylase Deficiency (BTD)

Clinical Features

Multiple carboxylase deficiency (MCD) is an inborn error of metabolism resulting from defective biotin metabolism. Juvenile (also called late) onset MCD (OMIM #253260) results from profound or partial deficiency of biotinidase, whereas early onset MCD (OMIM #253270) is caused by holocarboxylase synthetase deficiency. Both forms of MCD are responsive to biotin therapy. Making a distinction between the two types is difficult and relies largely on age of onset rather than clinical features. Clinical signs of juvenile onset MCD typically appear after 3 months of age while early onset MCD is typically evident earlier than 3 months of age (Wolf et al., 1985. PubMed ID: 4073853). In vitro enzyme studies are capable of distinguishing between the two disorders. The earliest presenting sign is usually seizures, but other early non-specific symptoms include hypotonia, respiratory symptoms, developmental delay, and ataxia. Eczema, alopecia, dermatitis, and skin infections are also common findings, and cutaneous presentations in conjunction with neurological symptoms greatly limit the differential diagnosis. Clinical variability is documented. Untreated patients with partial biotinidase deficiency may experience fewer and milder symptoms than patients with complete deficiency (Suormala et al., 1990. PubMed ID: 2109151). Asymptomatic adults with profound biotinidase deficiency have also been reported (Wolf et al., 1997. PubMed ID: 9375914).

Prevention

Immediate diagnosis and treatment of multiple carboxylase deficiency is often critical to normal growth and development. Recommended treatment is daily supplementation of biotin, which can prevent symptoms and may reverse some health problems (Smith and Heese, Kansas Department of Health and Environment; kdheks.gov/newborn_screening). Since symptoms of MCD are similar to several other metabolic complications, molecular confirmation is essential to confirm the correct diagnosis and begin treatment (Wolf, B., GeneReviews. 2011; ncbi.nlm.nih.gov/books/NBK1322).

Biotin Supplementation

All children exhibiting symptoms of MCD show great improvements when treated with 5-10 mg oral biotin per day. They also remain asymptomatic if biotin therapy is instituted early and they are continuously maintained on this therapy (Wolf, B., GeneReviews. 2011; ncbi.nlm.nih.gov/books/NBK1322). However, if left untreated, children exhibit developmental delay and metabolic compromise, including ketolactic acidosis and organic academia which may ultimately result in coma or death. A delay in starting therapy can also result in irreversible neurological damage making early diagnosis and treatment essential (Wolf B., 1991. PubMed ID: 1779651).

For more information on BTD testing, please see our full Test Description.


Disclaimer

This article is a summary of information that has been reported in the biomedical research literature. It is not medical advice for patients. All disease treatments should be under the direction of a qualified healthcare provider.

Last Updated: 10/3/2017