MCD is inherited in an autosomal recessive pattern. Normally a person has two functional HLCS genes. In people with MCD, both genes have a mutation and there is a deficiency of the critical enzyme. Each parent of a newborn with MCD typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of MCD do not typically have symptoms.
The symptoms of MCD usually appear within the first few months of life, and include feeding difficulty, breathing problems, dermatitis, alopecia and lethargy. If untreated, MCD symptoms may include delayed developmental milestones, seizures, and coma.
- Incidence: MCD has an incidence of less than 1 in 100,000.
- New York State Method of Screening (First Tier): Screening for MCD is accomplished by measuring the acylcarnitines C3 (propionylcarnitine) and C5OH (hydroxyisovalerylcarnitine) by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: Newborn screening cannot distinguish between MCD and propionic acidemia, methylmalonic acidemia or severe maternal vitamin B12 deficiency.
- Interpretation/reporting of data: Results are reported as screen negative, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for MCD are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of MCD.
Diagnostic testing may include urine organic acid analysis, acylcarnitine profile, enzyme analysis and genetic testing of the HLCS gene.
The recommended treatment for MCD is biotin supplementation, which is very effective.
If biotin supplementation is started promptly, most children with MCD have normal growth and development and symptoms are prevented. A delay in treatment can not reverse symptoms that are already present. On treatment, the prognosis for babies diagnosed with MCD is good.
Multiple carboxylase deficiency (MCD) is a term used to describe inborn errors of biotin metabolism. There are two primary forms: biotinidase deficiency and holocarboxylase synthetase deficiency. Each of these causes reduced activity of biotin-dependent enzymes; specifically in holocarboxylase synthetase deficiency the defective enzyme is holocarboxylase synthetase. Mutations in the HLCS gene cause this defective enzyme which ultimately results in multiple carboxylase deficiency. Biotin-dependent carboxylases are involved in the breakdown of protein, fats and carbohydrates, therefore individuals with MCD have impaired metabolism of these substances.