What are the symptoms of BTD?

September 21, 2025 •

2 min read

Approximately 1 in 60,000 newborns worldwide are affected by Biotinidase Deficiency (BTD), a rare but treatable inherited metabolic disorder. This condition prevents the body from recycling the essential vitamin biotin, leading to a wide range of symptoms that can affect multiple systems in the body. Understanding what are the symptoms of BTD can lead to earlier diagnosis and life-changing treatment.

Quick Summary

Biotinidase deficiency (BTD) can cause symptoms such as skin rashes, hair loss (alopecia), seizures, weak muscle tone (hypotonia), developmental delays, breathing difficulties, hearing and vision problems, and a fungal infection called candidiasis. Symptom severity depends on whether the deficiency is profound or partial, and whether it is left untreated.

Key Points

Neurological Issues: Seizures, hypotonia (weak muscle tone), and developmental delays are common symptoms of untreated BTD.
Cutaneous Manifestations: Skin rashes, hair loss (alopecia), and chronic fungal infections like candidiasis are frequently observed.
Sensory Impairments: Untreated profound BTD can lead to irreversible sensorineural hearing loss and optic atrophy.
Profound vs. Partial: Symptom severity depends on the level of enzyme activity, with profound BTD causing more severe issues and partial BTD showing milder symptoms, often only during illness.
Importance of Early Treatment: Oral biotin supplementation, especially when started shortly after birth via newborn screening, can prevent the development of severe symptoms.
Late-Onset Symptoms: In rare cases, adults with untreated profound deficiency can develop myelopathy and optic neuropathy, sometimes initially mistaken for multiple sclerosis.

Understanding Biotinidase Deficiency (BTD)

Biotinidase deficiency (BTD) is a metabolic disorder caused by a genetic mutation in the BTD gene. This mutation results in a lack of the biotinidase enzyme, which is vital for releasing biotin from proteins. The body cannot recycle biotin effectively without this enzyme, impacting the metabolism of fats, carbohydrates, and proteins. This can cause various health problems with symptoms that vary in severity based on enzyme activity levels.

Profound vs. Partial Biotinidase Deficiency

BTD is classified into two types: profound and partial, based on the level of functional enzyme activity. Profound deficiency involves less than 10% of normal enzyme activity, leading to severe symptoms often appearing within the first year of life if untreated. Partial deficiency is characterized by 10–30% of normal enzyme activity, with milder symptoms that may only occur during periods of stress. Treatment is recommended for both types.

The Wide Spectrum of BTD Symptoms

Untreated BTD can manifest in diverse symptoms affecting multiple body systems. These include:

Neurological Symptoms

Seizures
Weak muscle tone (hypotonia)
Poor balance (ataxia)
Developmental delays
Progressive vision loss due to optic atrophy
Hearing loss
Spinal cord issues (myelopathy) in adults

Dermatological and Cutaneous Symptoms

Hair loss (alopecia)
Scaly, red skin rashes
Chronic fungal infections like candidiasis
Eye inflammation (conjunctivitis)

Respiratory and Metabolic Symptoms

Breathing difficulties, such as hyperventilation or apnea
Feeding problems
Metabolic acidosis (acid buildup in the body)

Comparison of Profound vs. Partial BTD Symptoms


Feature	Profound Biotinidase Deficiency	Partial Biotinidase Deficiency
Enzyme Activity	Less than 10% of normal	10–30% of normal
Symptom Onset	Typically within the first year of life	Often during periods of metabolic stress
Symptom Severity	Severe and multisystemic	Mild, or may be asymptomatic
Common Symptoms	Seizures, hypotonia, developmental delay, alopecia, skin rashes, hearing/vision loss	Milder versions of profound symptoms, triggered by stress or illness
Risk of Complications	High, including irreversible damage	Lower, but still present during stress

The Critical Importance of Early Diagnosis and Treatment

Newborn screening is vital for detecting BTD early. Prompt treatment with oral biotin supplementation is highly effective in preventing severe complications. Early-treated individuals generally have an excellent prognosis and can lead normal lives. However, delayed treatment can result in irreversible effects, such as hearing and vision loss.

What to Do If You Suspect BTD

If BTD is suspected, especially in a newborn, seek immediate medical attention from a metabolic specialist for proper diagnosis and management. Diagnosis involves measuring biotinidase enzyme activity in a blood sample. For further information, consult resources like the National Organization for Rare Disorders (NORD).

Conclusion

Biotinidase deficiency is a serious yet manageable genetic disorder with a broad spectrum of symptoms. Early detection through newborn screening and timely intervention with biotin supplementation are critical for preventing severe, potentially irreversible health issues. Understanding what are the symptoms of BTD is essential for achieving positive outcomes.

Frequently Asked Questions

BTD stands for Biotinidase Deficiency, a rare inherited metabolic disorder where the body cannot produce a sufficient amount of the biotinidase enzyme. This enzyme is needed to recycle the vitamin biotin, which is essential for proper metabolism.

Biotinidase deficiency is primarily diagnosed through newborn screening programs, which measure biotinidase enzyme activity from a small blood sample. If a positive result is found, further testing, such as genetic analysis, may be used for confirmation.

While BTD cannot be cured, it can be effectively managed with lifelong daily oral biotin supplementation. Treatment started early can prevent all symptoms from developing, but it must be continued for life.

If left untreated, profound BTD can lead to severe and potentially irreversible health problems, including seizures, developmental delays, vision and hearing loss, and neurological damage. In severe cases, it can lead to coma and death.

No. While people with profound BTD are at high risk of developing severe symptoms, individuals with partial BTD may only show mild symptoms during times of metabolic stress, and some may remain asymptomatic without treatment.

The incidence of BTD varies across different countries and populations. Some regions with higher rates of consanguinity, such as Turkey and Saudi Arabia, have a higher prevalence of the disorder.

While the underlying problem is a lack of available biotin, the symptoms of BTD can be more severe and wide-ranging than those of a simple dietary biotin deficiency, which is very rare in a healthy individual. BTD prevents the body from using biotin from any source, not just food.