Holocarboxylase synthetase deficiency

Testing should be considered for brothers and sisters of a child with holocarboxylase synthetase deficiency syndrome, even if they have no symptoms. Symptoms of holocarboxylase synthetase deficiency syndrome can start at different ages, even in the same family.

Carrier testing is also available to other family members when the changes in the HLCS gene have been identified in the family member with holocarboxylase synthetase deficiency syndrome.

Urine metabolic tests may be used to monitor holocarboxylase synthetase deficiency syndrome. Testing checks to see if there is any build-up of certain chemicals in the body related to the condition.

The diagnosis of holocarboxylase synthetase deficiency syndrome is suggested by urine organic acids analysis and confirmed by holocarboxylase synthetase enzyme assay or DNA mutation analysis.

A person with holocarboxylase synthetase deficiency syndrome should have periodic assessment by a clinical geneticist or metabolic specialist.

Holocarboxylase synthetase deficiency syndrome is often abbreviated as HCSD .

Holocarboxylase synthetase deficiency is an inherited disorder in which the body is unable to use the vitamin biotin effectively. People with this condition have trouble using biotin, a vitamin that helps turn certain carbohydrates and proteins into energy for the body. Holocarboxylase synthetase deficiency is considered an organic acid condition because it can lead to a harmful buildup of organic acids and toxins in the body if it is not treated.

The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onset varies. Affected infants often have difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy). Immediate treatment and lifelong management with biotin supplements may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizures, and coma. These medical problems may be life-threatening in some cases.

Some of the first health problems that may be noticed in holocarboxylase synthetase deficiency syndrome include abnormal breathing, skin rash, feeding problems, and low muscle tone.

The enzyme called holocarboxylase synthetase works with biotin and other enzymes in the body to help with the normal production and breakdown of proteins, fats, and carbohydrates. Mutations in the HLCS gene reduce the enzyme’s ability to attach biotin to these enzymes, preventing them from processing nutrients properly and disrupting many cellular functions. These defects lead to the serious medical problems associated with holocarboxylase synthetase deficiency.

The HLCS gene provides the instructions for making holocarboxylase synthetase. Mutations in the HLCS gene cause holocarboxylase synthetase deficiency. About 30 mutations in the HLCS gene have been identified in people with holocarboxylase synthetase deficiency. Many of the known mutations occur in a region of the enzyme that binds to biotin. These genetic changes reduce the enzyme’s ability to attach biotin to enzymes (called carboxylases) and histones. Without biotin, carboxylases are unable to process proteins, fats, and carbohydrates effectively. A lack of holocarboxylase synthetase activity may also affect other genes in the body that are important for normal development. Researchers believe that these defects in enzyme function underlie the breathing problems, skin rashes, and other characteristic signs and symptoms of holocarboxylase synthetase deficiency.

Holocarboxylase synthetase deficiency syndrome occurs when an enzyme called holocarboxylase synthetase (HCS) is either missing or not working properly. This enzyme is important for the effective use of biotin, a B vitamin found in foods such as liver, egg yolks, and milk. Holocarboxylase sythetase adds biotin to other enzymes (called carboxylases) so that they can change the food we eat into energy for the body. When the HCS enzyme is not working, certain harmful substances build up in the blood and urine. This can cause serious health problems.

Signs of holocarboxylase synthetase deficiency (MCD) usually begin in infancy, sometimes as early as the first few days of life. These signs include:

When the diagnosis of holocarboxylase synthetase deficiency is made following newborn screening the following evaluations are recommended:

The treatment for holocarboxylase synthetase deficiency syndrome is a daily supplement of biotin. Daily biotin supplementation can correct the imbalance in the biotin cycle in the most people with this condition. Early detection and treatment can often prevent the severe outcomes of this condition.

Testing for holocarboxylase synthetase deficiency syndrome is included as part of newborn screening in all US states.

Testing for holocarboxylase synthetase deficiency syndrome can be done in more than one way.

HLCS gene is the only gene that causes holocarboxylase synthetase deficiency syndrome. However, changes in another gene, called BTD, can cause a condition called biotinidase deficiency syndrome, which is very similar to holocarboxylase synthetase deficiency syndrome.

The exact number of people in the US with holocarboxylase synthetase deficiency syndrome is unknown.

Each year about 45 to 50 babies are born with holocarboxylase synthetase deficiency syndrome in the United States.

Holocarboxylase synthetase deficiency syndrome is inherited as an autosomal recessive condition. Each person has two copies of the HLCS gene in every cell of the body. For a person with holocarboxylase synthetase deficiency syndrome, both copies of the gene have mutations and are not working correctly. The parents of an individual with an holocarboxylase synthetase deficiency syndrome each carry one copy of the mutated HLCS gene, but they do not show signs and symptoms of the condition.

You can also search [link url="ClinicalTrials.gov” target=”_blank”>ClinicalTrials.gov for information on clinical studies related to holocarboxylase synthetase deficiency syndrome. Note: There may not be clinical trials specifically available for holocarboxylase synthetase deficiency syndrome.

Holocarboxylase synthetase deficiency syndrome is rare. It has been estimated to happen about 1 in 87,000 live births.

Each child with holocarboxylase synthetase deficiency syndrome is likely to experience slightly different effects. Many babies with this condition start to have symptoms within hours of birth or during the first few days or weeks of life. Other babies have their first symptoms sometime in infancy, usually before two years of age. A small number of people with holocarboxylase synthetase deficiency never show symptoms and are only found to be affected after a brother or sister is diagnosed.

Carriers of holocarboxylase synthetase deficiency syndrome do not need to take a biotin supplement. A carrier has one working copy of the HLCS gene, which is able to make enough holocarboxylase synthetase enzyme for normal body chemistry.

Each child with holocarboxylase synthetase deficiency syndrome is likely to experience slightly different effects and could have symptoms start at different times, even with the exact same genetic change in the HLCS gene.

Parents of a child with holocarboxylase synthetase deficiency syndrome each carry one copy of the HLCS gene that is not working. There is a 25% (1 in 4) chance for holocarboxylase synthetase deficiency syndrome in any child born to parents who are both carriers for this condition.

Newborn screening is expected to identify almost all cases of holocarboxylase synthetase deficiency syndrome. Occasionally a child who has not been screened or has been mistakenly thought to have normal newborn screening will present with clinical symptoms.

Holocarboxylase synthetase deficiency syndrome has also been called:

The following organizations offer resources and support to patients and families with holocarboxylase synthetase deficiency:http://www.oaanews.org/

A person with holocarboxylase synthetase deficiency syndrome should avoid eating raw eggs. The raw egg white contains a protein call avidin that binds with biotin and can make it unavailable to the body.

The symptoms of biotinidase deficiency and holocarboxylase synthetase deficiency are similar. They both change the way the body uses biotin and both conditions improve with biotin treatment. It is often difficult to tell them apart without specialized testing.