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Biotinidase Deficiency

Disease Details

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Description: Biotinidase deficiency is an inherited metabolic disorder that impairs the body's ability to recycle the vitamin biotin, leading to a range of neurological and skin symptoms.
Type: Biotinidase deficiency is a metabolic disorder. It follows an autosomal recessive pattern of genetic transmission.
Signs And Symptoms: Signs and symptoms of a biotinidase deficiency (BTD) can appear several days after birth. These include seizures, hypotonia and muscle/limb weakness, ataxia, paresis, hearing loss, optic atrophy, skin rashes (including seborrheic dermatitis and psoriasis), and alopecia. If left untreated, the disorder can rapidly lead to coma and death.Neonates with BTD may not exhibit any signs, and symptoms typically appear after the first few weeks or months of life. If left untreated, around 70% of infants with BTD will experience seizures (staring spells, jerking limb movements, stiffness, flickering eyelids), which often acts as the first symptom of BTD. Infants with BTD may also have weak muscles and hypotonia; this may cause infants to appear abnormally "floppy" and have affected feeding and motor skills. BTD may result in developmental delays, vision or hearing problems, eye infections, alopecia, and eczema. The urine of infants with BTD may contain lactic acid and ammonia. Other symptoms that infants may exhibit include ataxia, breathing issues, lethargy, hepatomegaly, splenomegaly, and speech problems. The condition may eventually result in a coma and death.Biotinidase deficiency can also appear later in life. This is referred to as "late-onset" biotinidase deficiency. The symptoms are similar, but perhaps more mild, because if an individual survives the neonatal period they likely have some residual activity of biotin-related enzymes. Studies have noted individuals who were asymptomatic until adolescence or early adulthood. One study pointed out that untreated individuals may not show symptoms until age 21. Furthermore, in rare cases, even individuals with profound deficiencies of biotinidase can be asymptomatic.Symptom severity is predictably correlated with the severity of the enzyme defect. Profound biotinidase deficiency refers to situations where enzyme activity is 10% or less. Individuals with partial biotinidase deficiency may have enzyme activity of 10–30%.Functionally, there is no significant difference between dietary biotin deficiency and genetic loss of biotin-related enzyme activity. In both cases, supplementation with biotin can often restore normal metabolic function and proper catabolism of leucine and isoleucine.The symptoms of biotinidase deficiency (and dietary deficiency of biotin) can be quite severe. A 2004 case study from Metametrix detailed the effects of biotin deficiency, including aggression, cognitive delay, and reduced immune function.
Prognosis: Biotinidase deficiency is a rare inherited disorder that impairs the body's ability to recycle the vitamin biotin. The prognosis varies depending on the promptness of diagnosis and treatment. With early detection and proper biotin supplementation, individuals typically have a normal life expectancy and can lead healthy lives. Without treatment, the condition can lead to irreversible neurological and developmental complications. Early intervention is crucial for a favorable outcome.
Onset: Biotinidase deficiency typically presents at birth or in early infancy, though late-onset forms can occur. The severity and timing of symptoms can vary widely.
Prevalence: Biotinidase deficiency is a rare inherited disorder with a prevalence of approximately 1 in 60,000 newborns.
Epidemiology: Based on the results of worldwide screening of biotinidase deficiency in 1991, the incidence of the disorder is:
5 in 137,401 for profound biotinidase deficiency

One in 109,921 for partial biotinidase deficiency
One in 61,067 for the combined incidence of profound and partial biotinidase deficiency
Carrier frequency in the general population is approximately one in 120.
Intractability: Biotinidase deficiency is not considered intractable. It can be effectively managed with early diagnosis and lifelong supplementation of biotin, which prevents symptoms and allows individuals to lead normal, healthy lives. Without treatment, the disease can lead to serious complications, but with proper management, the prognosis is generally very positive.
Disease Severity: Biotinidase deficiency is a rare, inherited metabolic disorder that affects the body’s ability to recycle the vitamin biotin. The severity of the disease can be classified as:

1. **Profound (Severe) Biotinidase Deficiency:** Individuals have less than 10% of normal enzyme activity. Symptoms may include seizures, muscle weakness, developmental delays, hearing and vision loss, skin rashes, and alopecia. These symptoms typically appear within the first few months of life if untreated.

2. **Partial Biotinidase Deficiency:** Individuals have between 10% to 30% of normal enzyme activity. Symptoms are generally milder and may include skin rashes, hair loss, and developmental delays. These symptoms may become more apparent during periods of stress or illness.

With early diagnosis and treatment through biotin supplementation, individuals with biotinidase deficiency can lead normal, healthy lives.
Healthcare Professionals: Disease Ontology ID - DOID:856
Pathophysiology: Symptoms of the deficiency are caused by the inability to reuse biotin molecules that are needed for cell growth, production of fatty acids and the metabolism of fats and amino acids. If left untreated, the symptoms can lead to later problems such as comas or death. Unless treatment is administered on a regular basis, symptoms can return at any point during the lifespan.
Carrier Status: Carrier status for biotinidase deficiency refers to individuals who have one normal copy of the BTD gene and one mutated copy. These carriers do not typically show symptoms of the disease but can pass the mutated gene to their offspring. If both parents are carriers, there is a 25% chance that their child will have biotinidase deficiency.
Mechanism: Biotinidase deficiency is an inherited metabolic disorder caused by mutations in the BTD gene, which encodes the enzyme biotinidase. The enzyme's primary function is to recycle biotin from biotin-dependent carboxylases and dietary protein, essentially recovering and reusing biotin within the body.

**Mechanism:**
In biotinidase deficiency, the deficient or defective enzyme leads to an inadequate recycling of biotin, a crucial water-soluble B-vitamin. Biotin is a coenzyme for carboxylase enzymes necessary for various metabolic processes, including gluconeogenesis, fatty acid synthesis, and amino acid catabolism. Without sufficient biotin, these metabolic pathways are disrupted, leading to the accumulation of toxic metabolites and subsequent clinical symptoms.

**Molecular mechanisms:**
1. **Gene Mutation:** Mutations in the BTD gene affect the structure and function of the biotinidase enzyme. These mutations can result in either a complete absence of enzyme activity (profound deficiency) or partial activity (partial deficiency).

2. **Deficient Enzyme Activity:** When biotinidase activity is compromised, biotin cannot be efficiently recycled from biocytin or biotinylated peptides derived from degraded carboxylases. As a result, free biotin levels decrease.

3. **Impact on Carboxylase Enzymes:** Reduced availability of free biotin impairs the activation of biotin-dependent carboxylases. This affects key metabolic pathways:
- **Gluconeogenesis:** Impaired carboxylases lead to hypoglycemia because gluconeogenesis is disrupted.
- **Fatty Acid Synthesis and Oxidation:** Dysregulation in these pathways can cause abnormal skin rashes, alopecia, and neurological symptoms.
- **Amino Acid Catabolism:** Accumulation of toxic metabolites from amino acid catabolism can result in metabolic acidosis and exacerbation of neurological issues.

Early diagnosis and biotin supplementation can effectively manage the disorder, preventing most symptoms and ensuring normal metabolism.
Treatment: Treatment is possible but unless continued daily, problems may arise. Currently, this is done through supplementation of 5–10 mg of oral biotin a day. If symptoms have begun to show, standard treatments can take care of them, such as hearing aids for poor hearing.
Compassionate Use Treatment: Biotinidase deficiency is typically treated with biotin supplements, which are standard and effective. However, if discussing compassionate use or off-label treatments, there are no widely recognized alternative treatments outside of biotin supplementation because it directly addresses the metabolic issue at its core.

Experimental treatments beyond biotin supplementation are not well documented, as biotinidase deficiency treatment is highly effective and standard. Research is ongoing in understanding metabolic diseases more broadly, but there is currently no alternative treatment protocol for biotinidase deficiency outside of biotin supplementation.

For patients not responding to biotin alone or with compounded issues, integrated metabolic therapies personalized to individual needs may be explored under clinical guidance. Always consult with a medical professional to consider any emerging treatments.
Lifestyle Recommendations: For individuals with biotinidase deficiency, lifestyle recommendations include:

1. **Regular Monitoring:** Regular check-ups with a healthcare provider to monitor biotin levels and overall health.
2. **Biotin Supplementation:** Lifelong supplementation with biotin is necessary to prevent symptoms and complications.
3. **Dietary Management:** While general dietary restrictions are not required, maintaining a balanced diet can support overall health.
4. **Avoid Certain Medications:** Some anti-seizure medications can interfere with biotin metabolism, so they should be used cautiously and under a doctor's supervision.
5. **Awareness and Education:** Individuals and caregivers should be educated about the condition to recognize symptoms of deficiency and seek prompt medical care if needed.

By adhering to these recommendations, individuals with biotinidase deficiency can lead healthy and active lives.
Medication: For biotinidase deficiency, the primary treatment is biotin supplementation. High doses of biotin, often ranging from 5 to 10 mg per day, can effectively manage symptoms and prevent complications, as individuals with this condition cannot properly recycle biotin. This treatment is typically lifelong.
Repurposable Drugs: Biotinidase deficiency is a metabolic disorder where the body cannot recycle the vitamin biotin. Treatment primarily involves biotin supplementation, which is effective in managing symptoms if started early. There isn't a well-documented list of repurposable drugs for biotinidase deficiency beyond biotin itself. Early detection and consistent biotin administration are critical for managing the condition.
Metabolites: Biotinidase deficiency is a disorder where the body cannot recycle the vitamin biotin. This leads to a shortage of free biotin necessary for essential enzymatic reactions. The primary metabolites affected by this condition are:

1. **Lactate**: Elevated levels can occur due to impaired energy metabolism.
2. **3-Hydroxyisovaleric acid**: Increased concentrations can be found in urine.
3. **3-Methylcrotonylglycine**: Also elevated due to disrupted pathways involving biotin-dependent enzymes.
4. **Propionylglycine**: Levels may rise in response to improper metabolism of certain amino acids and fatty acids.

Monitoring these metabolites helps in diagnosing and managing biotinidase deficiency.
Nutraceuticals: For biotinidase deficiency, the primary treatment involves biotin (vitamin B7) supplementation rather than nutraceuticals. Patients typically require lifelong biotin supplementation to prevent symptoms related to the deficiency. Nanotechnology is not currently a standard part of the management or treatment for biotinidase deficiency.
Peptides: Biotinidase deficiency is a metabolic disorder that results from a deficiency in the enzyme biotinidase, which is responsible for recycling biotin, a B-vitamin essential for various carboxylase enzymes in the body. Without adequate biotinidase activity, free biotin is not released from proteins and peptides. This leads to a deficiency that can cause neurological and dermatological symptoms.

"Peptides" refers to short chains of amino acids. In the context of biotinidase deficiency, peptides bound to biotin cannot be effectively processed to release free biotin due to the lack of functional enzyme.

"Nan" typically stands for "not a number" in computational contexts, but in this medical context, it may not be directly relevant or likely a misunderstanding or miscommunication without further context.