Biotinidase deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Biotinidase deficiency is an inherited disorder in which the body is unable to recycle the vitamin biotin. If this condition is not recognized and treated, its signs and symptoms typically appear within the first few months of life, although it can also become apparent later in childhood.

Profound biotinidase deficiency, the more severe form of the condition, can cause seizures, weak muscle tone (hypotonia), breathing problems, hearing and vision loss, problems with movement and balance (ataxia), skin rashes, hair loss (alopecia), and a fungal infection called candidiasis. Affected children also have delayed development. Lifelong treatment can prevent these complications from occurring or improve them if they have already developed.

Partial biotinidase deficiency is a milder form of this condition. Without treatment, affected children may experience hypotonia, skin rashes, and hair loss, but these problems may appear only during illness, infection, or other times of stress.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the BTD gene cause biotinidase deficiency. The BTD gene provides instructions for making an enzyme called biotinidase. This enzyme recycles biotin, a B vitamin found in foods such as liver, egg yolks, and milk. Biotinidase removes biotin that is bound to proteins in food, leaving the vitamin in its free (unbound) state. Free biotin is needed by enzymes called biotin-dependent carboxylases to break down fats, proteins, and carbohydrates. Because several of these enzymes are impaired in biotinidase deficiency, the condition is considered a form of multiple carboxylase deficiency.

Mutations in the BTD gene reduce or eliminate the activity of biotinidase. Profound biotinidase deficiency results when the activity of biotinidase is reduced to less than 10 percent of normal. Partial biotinidase deficiency occurs when biotinidase activity is reduced to between 10 percent and 30 percent of normal. Without enough of this enzyme, biotin cannot be recycled. The resulting shortage of free biotin impairs the activity of biotin-dependent carboxylases, leading to a buildup of potentially toxic compounds in the body. If the condition is not treated promptly, this buildup damages various cells and tissues, causing the signs and symptoms described above.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the BTD gene in each cell have mutations. The parents of an individual with biotinidase deficiency each carry one copy of the mutated gene, but they typically do not have any health problems associated with the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Profound or partial biotinidase deficiency occurs in approximately 1 in 60,000 newborns

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Decreased biotinidase activity · Very frequent (99-80%)

Concentration of biotinidase in the blood circulation below the lower limit of normal. Biotidinase is an enzyme that releases biotin from biocytin, the product of biotin-dependent carboxylases degradation.

Metabolic ketoacidosis · Very frequent (99-80%)

A metabolic acidosis due to accumulation of ketone bodies generally observed in the setting of poor nutritional intake.

Organic aciduria · Very frequent (99-80%)

Excretion of non-amino organic acids in urine.

Abnormality of the immune system · Frequent (79-30%)

An abnormality of the immune system.

Abnormality of the nervous system · Frequent (79-30%)

An abnormality of the nervous system.

Brain imaging abnormality · Frequent (79-30%)

An anomaly of metabolism or structure of the brain identified by imaging.

Hyperammonemia · Frequent (79-30%)

An increased concentration of ammonia in the blood.

Hypotonia · Frequent (79-30%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Seizure · Frequent (79-30%)

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

Sensorineural hearing impairment · Frequent (79-30%)

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

Skin rash · Frequent (79-30%)

A red eruption of the skin.

Abnormality of the eye · Occasional (29-5%)

Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Alopecia · Occasional (29-5%)

A noncongenital process of hair loss, which may progress to partial or complete baldness.

Apnea · Occasional (29-5%)

Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.

Other findings in the same source

From: Orphanet

Additional reported features include Ataxia (Occasional (29-5%)); Bilateral tonic-clonic seizure (Occasional (29-5%)); Conjunctivitis (Occasional (29-5%)); Eczematoid dermatitis (Occasional (29-5%)); Focal motor seizure (Occasional (29-5%)); Generalized myoclonic seizure (Occasional (29-5%)); Global developmental delay (Occasional (29-5%)); Hearing impairment (Occasional (29-5%)); Hyperventilation (Occasional (29-5%)); Infantile spasms (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Biotinidase deficiency is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.