Holocarboxylase synthetase deficiency is an
inherited metabolic disorder
A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter the ...
in which the body is unable to use the
vitamin
A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nut ...
biotin effectively.
This disorder is classified as a
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:
* Holocarboxylas ...
, a group of disorders characterized by impaired activity of certain
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
s that depend on biotin. Symptoms are very similar to
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.
Biotin is ...
and treatment – large doses of biotin – is also the same.
Symptoms and signs
Genetics
Mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...
s in the ''HLCS''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
cause holocarboxylase synthetase deficiency. The ''HLCS'' gene makes an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
,
holocarboxylase synthetase
Holocarboxylase synthetase (biotin—(propionyl-Coenzyme A-carboxylase (ATP-hydrolysing)) ligase)), also known as protein—biotin ligase, is a family of enzymes ({{{EnzExplorer, 6.3.4.10). This enzyme is important for the effective use of bio ...
, that attaches biotin to other molecules. Biotin, a
B vitamin
B vitamins are a class of water-soluble vitamins that play important roles in cell metabolism and synthesis of red blood cells. Though these vitamins share similar names (B1, B2, B3, etc.), they are chemically distinct compounds that often coexis ...
, is found in foods such as
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
,
egg yolk
Among animals which produce eggs, the yolk (; also known as the vitellus) is the nutrient-bearing portion of the egg whose primary function is to supply food for the development of the embryo. Some types of egg contain no yolk, for example bec ...
s, and
milk
Milk is a white liquid food produced by the mammary glands of mammals. It is the primary source of nutrition for young mammals (including breastfed human infants) before they are able to digest solid food. Immune factors and immune-modulati ...
. It is essential for the normal production and breakdown of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
s,
fat
In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food.
The term often refers specifically to triglycerides (triple es ...
s, and
carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ...
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
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...
pattern, which means two copies of the gene in each cell are altered.
Diagnosis
The signs and symptoms of holocarboxylase synthetase deficiency typically appear within the first few months of life, but the
age of onset
The age of onset is the age at which an individual acquires, develops, or first experiences a condition or symptoms of a disease or disorder. For instance, the general age of onset for the spinal disease scoliosis is "10-15 years old," meaning ...
varies. Affected infants often have immunodeficiency diseases, difficulty feeding, breathing problems, a skin
rash
A rash is a change of the human 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, cr ...
, hair loss (
alopecia
Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarr ...
), and a lack of energy (
lethargy
Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwor ...
). 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
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...
s, and
coma
A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
. These medical problems may be life-threatening in some cases.
Treatment
See also
*
List of cutaneous conditions
Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier agai ...
References
''This article incorporates public domain text fro
The U.S. National Library of Medicine'
External links
{{Metabolic disorders of vitamins, coenzymes, and cofactors
Autosomal recessive disorders
Vitamin, coenzyme, and cofactor metabolism disorders
Genodermatoses
Rare diseases