Biotinidase deficiency

Biotinidase deficiency is a rare autosomal recessive condition in which the body is unable to break down the conjugated form of the vitamin B₇ (biotin), resulting in low levels of available biotin.

Epidemiology

Profound deficiency (<10% of normal level) is estimated at ~1:100,000 of newborns. Profound or partial deficiency (<30% of normal level) is estimated at ~1:60,000 newborns.

Clinical presentation

Symptoms usually present in infancy with ⁴:

• lethargy
• anorexia
• hypotonia
• developmental delay
• alopecia
• seborrhoeic dermatitis
• conjunctivitis and mucositis
• erythematous rash
• hypotonia
• seizures
• hearing loss
• ataxia
• lactic acidaemia

Radiographic features

Variable neurologic manifestations:In biotinidase deficiency in children the neuroimaging findings are relatively non-specific ⁴.

• diffuse cerebral and cerebellarwhite matter atrophy on CT
• dilation of the ventricles and extra-axial CSF spaces

MRI

• T1:
  • diffuse or MRIpatchy signal abnormalities within cerebral and cerebellar white matter
  • brainstem andsub-cortical cyst formation
• T2: 
  • the same changes as above
  • signal abnormalities of the spinal cord myelopathymay also be seen
• DWI: areas of restricted diffusion within the signal abnormalities
• MR spectroscopy:
  • sometimes elevated lactate
  • reduced NAA

Treatment and prognosis

Improves with supplemental biotin, which helps with diagnosis.

Biotinidase deficiency meets the major criteria for newborn screening in multiple countries.

Differential diagnosis

• Leigh disease
• pyruvate dehydrogenase deficiency
• cytochrome c oxidase deficiency
• type I glutaric acidaemia
• spinal cord signal changes may mimic neuromyelitis optica