biotinidase deficiency

Biotinidase deficiency is a late-onset form of multiple carboxylase deficiency, an inherited metabolic condition that affects the body’s ability to recycle biotin. The condition results from pathogenic variants in the BTD gene, which disrupt the production of the biotinidase enzyme. Affected individuals, typically presenting in childhood rather than infancy, may experience a range of neurological and systemic symptoms. It is considered uncommon, affecting roughly 1 to 9 individuals per 100,000 people.

Clinically, biotinidase deficiency manifests with a variety of features that involve multiple organ systems. Neurologically, many affected individuals experience global developmental delay and seizures, while motor difficulties such as hypotonia and ataxia are frequently observed. Other characteristic findings include episodes of metabolic ketoacidosis, hyperammonemia, and ocular issues such as optic atrophy along with conjunctivitis. In addition, skin rash and alopecia are common, and as with many conditions, not all individuals experience all features, with severity varying considerably.

The underlying cause of biotinidase deficiency is linked to variants in the BTD gene, which encodes the biotinidase enzyme essential for recycling the vitamin biotin. This enzyme deficiency impairs the body’s ability to utilize biotin effectively, leading to the buildup of metabolic abnormalities. The condition is inherited in an autosomal recessive manner, meaning that an affected individual has inherited two altered copies of the gene, one from each parent. Families are encouraged to consider genetic counseling to discuss recurrence risks and explore carrier testing options.

Currently, management focuses on supportive care and symptom management, with treatment tailored to individual needs. Although there are no FDA-approved or foundational therapies specifically for biotinidase deficiency, a multidisciplinary team is typically involved to address neurological, metabolic, and other systemic complications. Regular surveillance is an essential part of long-term care, with ongoing monitoring helping to detect potential complications early. Patients and families are advised to discuss all available treatment options and supportive strategies with their healthcare team, including the possible benefits of consulting with specialists experienced in metabolic disorders.

The overall outlook for individuals with biotinidase deficiency can vary significantly, with outcomes depending on the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care, many individuals experience stabilization of their symptoms, although the condition may progress in some cases. That severity and symptoms vary widely between individuals, and ongoing monitoring remains critical. Families are encouraged to connect with genetic counselors and specialists who can provide guidance as understanding and management strategies continue to evolve.

There are clinical trials underway exploring new treatment approaches for biotinidase deficiency. Individuals interested in learning more about these trials are encouraged to consult ClinicalTrials.gov or discuss potential eligibility with their healthcare team.