Holocarboxylase synthetase deficiency
Encyclopedia
Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to use the vitamin
Vitamin
A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. In other words, an organic chemical compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on...
biotin
Biotin
Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin discovered by Bateman in 1916. It is composed of a ureido ring fused with a tetrahydrothiophene ring. A valeric acid substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring...
effectively. This disorder is classified as a multiple carboxylase deficiency
Multiple carboxylase deficiency
Multiple carboxylase deficiency is a form of metabolic disorder involving failures of carboxylation enzymes.The deficiency can be in biotinidase or holocarboxylase synthetase.These conditions respond to biotin.Forms include:...
, a group of disorders characterized by impaired activity of certain enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that depend on biotin. Symptoms are very similar to biotinidase deficiency
Biotinidase deficiency
Biotinidase deficiency is an autosomal recessive metabolic disorder in which biotin is not released from proteins in the diet during digestion or from normal protein turnover in the cell. This situation results in biotin deficiency....
and treatment – large doses of biotin – is also the same.
Diagnosis
The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the age of onsetAge of onset
The age of onset is a medical term referring to the age at which an individual acquires, develops, or first experiences a condition or symptoms of a disease or disorder...
varies. Affected infants often have immunodeficiency diseases, difficulty feeding, breathing problems, a skin rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, hair loss (alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
), and a lack of energy (lethargy). Immediate treatment and lifelong management (using biotin supplements) may prevent many of these complications. If left untreated, the disorder can lead to delayed development, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, and coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
. These medical problems may be life-threatening in some cases.
Genetics
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in the HLCS gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
cause holocarboxylase synthetase deficiency. The HLCS gene makes an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
, holocarboxylase synthetase, that attaches biotin to other molecules. Biotin, a B vitamin, is found in foods such as liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, egg yolk
Egg yolk
An egg yolk is a part of an egg which feeds the developing embryo. The egg yolk is suspended in the egg white by one or two spiral bands of tissue called the chalazae...
s, and milk
Milk
Milk is a white liquid produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals before they are able to digest other types of food. Early-lactation milk contains colostrum, which carries the mother's antibodies to the baby and can reduce the risk of many...
. It is essential for the normal production and breakdown of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, fat
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s, and carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s in the body. Mutations in the HLCS gene reduce the activity of holocarboxylase synthetase, preventing cells from using biotin effectively and disrupting many cellular functions.
This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered.