Biotinidase Deficiency Workup

Updated: Jul 27, 2018
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Laboratory Studies

In neonates, biotinidase deficiency is identified via newborn metabolic screening (activity assay). Mutational assay identifies the BTD mutation.

When biotinidase deficiency is suspected in a patient, obtain laboratory studies to test for an inborn error of metabolism.

Recommended serum tests include the following:

  • Arterial blood gas (ABG)

  • Serum chemistries

  • Ammonia level

  • Biotinidase, carnitine, and acylcarnitine profiles
  • Serum amino acids (SAA)

Recommended urine tests include the following:

  • Urine ketones

  • Urine organic acids (UOA)

Illness or catabolic stress can induce metabolic disruption. Obtaining laboratory studies at this time may give clues to the etiology of a metabolic disorder. These clues may resolve in an otherwise healthy child, especially in patients who have partial biotinidase enzyme activity. Affected children may have ketolactic acidosis, organic aciduria, and/or mild hyperammonemia. [1]


Imaging Studies

Magnetic resonance imaging (MRI) is the neuroimaging study of choice to evaluate a child with a possible inborn error of metabolism. Children with biotinidase deficiency may show cerebral edema, low attenuation of white matter signal, cerebral atrophy, and compensatory ventricular enlargement. [29]

Magnetic resonance spectroscopy (MRS) helps determine functional brain metabolism. Some hospital facilities have access to MRS, and using this tool may help delineate the nature of the brain disorder in vivo.

Positron emission tomography (PET) scanning is used to demonstrate changes in cerebral metabolic activity before and after administration of biotin therapy.

Computerized tomography (CT) scanning may demonstrate bilateral basal ganglia calcifications that may not be as easily observed on MRI.


Other Tests


Electroencephalography (EEG) findings prior to biotin treatment demonstrate poor organization of background and absence of typical sleep morphology.

Ictal manifestations have been described as diffuse polyspike discharges at the onset of seizures (myoclonic) followed by rhythmic diffuse spike and wave discharges during clinical presentation of a generalized tonic-clonic seizure. [22]

EEG findings vary and may normalize completely after biotin therapy.

Ophthalmologic testing

An experienced ophthalmologist should perform a dilated funduscopic examination to evaluate for optic nerve atrophy and scotomata.

Visual field testing and visual evoked potentials (VEPs) may help determine the degree of optic nerve injury in affected patients.

Audiologic testing

Perform audiologic testing in all children, as hearing deficits in symptomatic children are common and can persist after treatment.

Brainstem auditory evoked response (BAER) potentials may help delineate hearing impairment in young children or in patients with development or speech delay.


Histologic Findings

The extent of pathologic central nervous system (CNS) lesions in patients with biotinidase deficiency vary based on the severity of their clinical condition prior to death. Findings are similar to those found in Leigh syndrome or Wernicke encephalopathy, although the pathologic lesions in the CNS appear more widespread.

Myelin appears to be more severely affected than neurons or axonal processes. Poorly delineated necrotic lesions affect the pons, hypothalamus, hippocampus, and medulla. Microscopically, these areas show microcavitation, capillary proliferation, and gliosis.

Severe cerebral edema may be evident in many major white matter tracts.