Biotinidase Deficiency Workup

  • Author: Ronald G Davis, MD, MPH, FAAP; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 27, 2012
 

Laboratory Studies

  • Upon presentation of suspected biotinidase deficiency, obtain laboratory studies to determine if an inborn error of metabolism is present. These studies are detailed below.
  • Illness or catabolic stress may cause metabolic disruption, and obtaining laboratory studies at that time may provide clues to the etiology of the disorder.
  • Obtaining samples during the illness is important because these clues may disappear in the otherwise healthy child, especially in one with partial enzyme deficiency.
  • Specific tests include the following:
    • Serum ammonia
    • Urine organic acids
    • Plasma amino acids
    • Urine ketones
    • Blood gas
    • Serum chemistries
    • Biotinidase, carnitine, and acylcarnitine profiles
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Imaging Studies

  • MRI is the neuroimaging study of choice for the evaluation of a child with a possible inborn error of metabolism. Children with biotinidase deficiency may demonstrate cerebral edema, low attenuation of white matter signal, cerebral atrophy, and compensatory ventricular enlargement.[12]
  • Magnetic resonance spectroscopy also helps determine the functional metabolism of the brain. Some facilities have access to these techniques and using them may help to delineate the nature of the brain disorder in vivo.
  • Positron emission tomography is used in an experimental setting to demonstrate the change in cerebral metabolic activity before and after biotin therapy.
  • CT scan may demonstrate bilateral basal ganglia calcifications that may not be as readily demonstrated on MRI.
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Other Tests

  • Ophthalmologic testing
    • An experienced ophthalmologist should perform a dilated funduscopic examination to evaluate for optic atrophy.
    • Visual field testing and visual evoked potentials may help to 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 be persistent after treatment.
    • Brainstem auditory evoked potentials may help to delineate the abnormality in younger children or in developmentally delayed patients.
  • Electroencephalography
    • EEG findings prior to treatment demonstrate poor organization of background and absence of typical sleep morphology.
    • Frequent focal spikes were observed in 1 child during the interictal period.
    • Ictal manifestations were well described in 1 report, demonstrating diffuse polyspike discharges at the onset of seizures (myoclonic) followed by the appearance of rhythmic diffuse spike and wave discharges during clinical manifestations of a generalized tonic-clonic seizure.
    • EEG findings are variable and may normalize completely after therapy.
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Histologic Findings

  • Pathological lesions in biotinidase deficiency vary probably based on the severity of the illness preceding death.
  • Findings are similar to those found in Leigh syndrome or Wernicke encephalopathy, although the pathological lesions appear to be more widespread in the CNS.
  • Poorly delineated necrotic lesions widely affect the pons, hypothalamus, hippocampus, and medulla. Viewed microscopically, these areas showed microcavitation, capillary proliferation, and gliosis.
  • Myelin appears to be more severely affected than neurons or axonal processes.
  • Severe edema may be evident in many major white matter tracts.
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Contributor Information and Disclosures
Author

Ronald G Davis, MD, MPH, FAAP  Assistant Clinical Professor, Child Neurology, Florida State University; Owner and Medical Director of Pediatric Neurology, PA and Pediatric Neurology Epilepsy Center of Central Florida; Medical Director of Epileptology, Arnold Palmer Hospital for Women and Children in Orlando, Florida; Medical Director, Central Florida Muscular Dystrophy Association Clinic

Ronald G Davis, MD, MPH, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society

Disclosure: Nothing to disclose.

Coauthor(s)

Marc P DiFazio, MD  Associate Professor, Department of Neurology, Uniformed Services University of the Health Sciences; Director, Pediatric Subspecialty Services, Shady Grove Adventist Hospital for Children

Marc P DiFazio, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Cerebral Palsy and Developmental Medicine, American Academy of Neurology, Child Neurology Society, and Movement Disorders Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Christian J Renner, MD  Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD  Professor and Chair of Pediatrics, Stony Brook University, New York

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics

Disclosure: Genzyme Grant/research funds PI

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

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