About carboxylase deficiency, multiple

What is carboxylase deficiency, multiple?

Biotinidase deficiency (BTD) is a treatable, metabolic disorder that is the result of a low concentration, or complete lack, of the enzyme, biotinidase. Biotinidase deficiency is an inherited disorder in which the body is not able to properly process the vitamin, biotin, which is sometimes referred to as Vitamin H. Biotin is an essential vitamin to the metabolic process and biotinidase, among its other functions, allows biotin to become available for use by the body. Mutations in the BTD gene cause biotinidase deficiency. The genetic traits associated with biotinidase deficiency are transmitted in an autosomal recessive manner.

Most infants with BTD show signs of lactic acid in the urine (aciduria), a widespread, red, skin rash (eczema), seizures, poor muscle tone (hypotonia), developmental delays, and hair loss (alopecia). Daily treatment with biotin supplements will clear up these symptoms.

What are the symptoms for carboxylase deficiency, multiple?

Multiple carboxylase deficiency (MCD) is a crucial metabolic disorder that occurs when there is a lack of coenzyme activity of biotin.

  • The usual genetic causes of multiple carboxylase deficiency involve biotinidase deficiency and holocarboxylase synthetase (HCS) deficiency.
  • A deficiency is evident in the biotin-dependent enzymes (methylcrotonyl-CoA carboxylase, pyruvate carboxylase, and propionyl-CoA carboxylase) due to two specific defects in biotin metabolism.
  • The neonatal form is marked as Holocarboxylase Synthetase Deficiency, while the late-onset form is referred to as Biotinidase Deficiency.


Symptoms

  • Infants with Holocarboxylase Synthetase Deficiency become symptomatic within the first few weeks of their life.
  • The symptoms are likely to appear as early as a few hours after birth to as late as 7-8 years of age.
  • Shortly after birth, the clinical symptoms in the affected infants include apnea and tachypnea (breathing difficulties).
  • This is accompanied by Vomiting, feeding problems, and hypotonia.
  • If this condition remains untreated, generalized erythematous rash along with alopecia and exfoliation may occur.
  • In some instances, Irritability, failure to thrive, Lethargy, Seizures, and coma are also evident.
  • Developmental delay is common along with immune deficiency, which manifests with susceptibility to different infections.
  • Urine possesses a significant odor referred to as tomcat urine.


Conditions
Dermatologic manifestations,Alopecia,Rashes,Mucocutaneous candidiasis
Drugs
Biotin (10-20 mg/day orally)
Symptoms
Lethargy,Hypotonia,Seizures,Difficulty feeding,Breathing,Vomiting,Developmental delays,Ataxia,Seizures,Coma

What are the causes for carboxylase deficiency, multiple?

Carboxylase is the enzyme that regulates according to sufficient levels of significant Vitamin Biotin. This vitamin and its functioning cofactors four different carboxylases in a body's formation of proteins, fats, and carbohydrates while breaking down. The process is called Holocarboxylase Synthetase. But the defect in this process is called Multiple Carboxylase Deficiency (MCD).

  • A cell enzyme called Biotinidase is responsible for collecting and recycling the biotin left from attaching (coenzyme/cofactor) process.
  • As the biotin left is free, it is used again for the Holocarboxylase Synthetase.
  • Functioning suggests how the deficiency of biotin and its enzymes can affect a child's growth and the body's ability to digest food components effectively.


Causes/Reasons for MCD:

There is no specific reason for this rare autosomal recessive disease. But most prominently seen:

  • MCD is more likely congenital.
  • Changes in the HLCS gene due to copies of the defected gene in parents carry this defect in a child.
  • The inability to produce biotin by a defected body enhances the disability further.
  • The underdeveloped system disrupts the whole mechanism of processing nutrients and cellular formations.


Early detections and treatments with inducing biotin supplements suggested by doctors proved beneficial for a patient's life span.

Conditions
Dermatologic manifestations,Alopecia,Rashes,Mucocutaneous candidiasis
Drugs
Biotin (10-20 mg/day orally)
Symptoms
Lethargy,Hypotonia,Seizures,Difficulty feeding,Breathing,Vomiting,Developmental delays,Ataxia,Seizures,Coma

What are the treatments for carboxylase deficiency, multiple?

Deficiency related to digestive enzymes produced in the human body is Multiple Carboxylase Deficiency. This rare disorder is either detected at birth or till the age of eight years. Slow growth and constant illness are the results of this defect if not treated on time.

Diagnosis:

Distinct processes were invented to detect MCD in infants and onset patients to start the treatments at the earliest.

  • A compulsory detection procedure of Multiple Carboxylase Deficiency checks for all newly born babies.
  • This process is called Newborn Screening Service.


Other tests include:

  • Plasma Profile
  • Serum Assay
  • Urine Organic Acids
  • DNA testing
  • WBC (white blood cells)
  • Fibroblasts


Laboratory Results:

Initial symptoms are enough to understand the familiarity and diagnosis of this rare disease. Yet doctors, prefer lab results as follows:

  • Level of Ammonia
  • Strong odored urine
  • Abnormal urine organic acids


Treatment:

As for now, there are no specific drugs or medications available for curing this genetic disorder. Preventions and drugs for the symptoms are given to a patient for effective recovery:

  • Prescribed Biotin dosages according to age (20-300 mg per day)
  • Avoid Starving
  • Special Counselling from beginning
  • Regular hearing and growth checkups
  • Rapid Actions on fever and other infections


Conditions
Dermatologic manifestations,Alopecia,Rashes,Mucocutaneous candidiasis
Drugs
Biotin (10-20 mg/day orally)
Symptoms
Lethargy,Hypotonia,Seizures,Difficulty feeding,Breathing,Vomiting,Developmental delays,Ataxia,Seizures,Coma

What are the risk factors for carboxylase deficiency, multiple?

The human body mechanism is a marvel illustration of engineering. All the systems are perfectly designed to send and receive signals for every activity required for a body. Such is our digestive system, where carboxylase enzymes are attached with Vitamin Biotin to process the components of our foods.

A defect in the process of recycling biotin; results in insufficient enzymes and biotin and ultimately results in Multiple Carboxylase Deficiency (MCD).

Factors of MCD:

The perfect metabolism and structured development of the body since birth depends on the correct levels of all the substances present in our body.

  • MCD is a rare autosomal recessive disorder.
  • It occurs with changes and mutations in HLCS genetic patterns.
  • This development is not a positive one and demeans growth at particular levels.
  • Mutations in HLCS genes kill the force between enzymes and biotics that leading to incomplete digestion processes.


Risk factors:

Disorders with deep and rare genetic mutations have very few external risk factors. The following figures support this statement as follows:

  • Inheritance: A couple with an MCD child will have a 25% chance of a child with a similar disorder in their future pregnancy.
  • Incidence: Chances are 1 in 80,000 to 1 in 1,20,000 person may suffer from MCD.


So every risk is related to the hereditary transmission and copies of genes from the parents.

Conditions
Dermatologic manifestations,Alopecia,Rashes,Mucocutaneous candidiasis
Drugs
Biotin (10-20 mg/day orally)
Symptoms
Lethargy,Hypotonia,Seizures,Difficulty feeding,Breathing,Vomiting,Developmental delays,Ataxia,Seizures,Coma

Is there a cure/medications for carboxylase deficiency, multiple?

Multiple carboxylase deficiency is an uncommon inborn biotin metabolic error caused by biotinidase or holocarboxylase synthetase abnormalities in the biotin cycle.

  • 3-methylcrotonyl carboxylase, propionyl-CoA carboxylase, acetyl-CoA carboxylase, and pyruvate carboxylase all require biotin as a cofactor.
  • The covalent attachment of biotin to the 4 carboxylases is catalysed by holocarboxylase synthetase, which activates the enzymes.
  • Biotinyl-lysine is generated when caboxylases are destroyed. Biotinidase catalyses the restoration of protein-bound biotin by hydrolyzing biotnyl-lysine and releasing free biotin, which is then recycled to activate freshly produced carboxlyase enzymes.


Treatment

  • Biotin supplementation can prevent the systemic abnormalities caused by holocarboxylase synthetase and biotinidase deficits.
  • Biotin 5-10mg per day is administered orally to newborns.
  • As the child grows, the biotin dose by mouth can be raised to 15-20mg per day.
  • Biotin is available in tablet and liquid formulations. Biotin can be added to cereal or other foods in tiny doses.
  • Adults may be given up to 100mg per day.
  • Although the optimal biotin amount is unknown, the existing amount is empirical and may be modified as the child develops.
  • The present levels are not entirely research-based; however, there is no indication of biotin toxicity.


Conditions
Dermatologic manifestations,Alopecia,Rashes,Mucocutaneous candidiasis
Drugs
Biotin (10-20 mg/day orally)
Symptoms
Lethargy,Hypotonia,Seizures,Difficulty feeding,Breathing,Vomiting,Developmental delays,Ataxia,Seizures,Coma

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