Krabbe Disease Clinical Presentation

  • Author: David H Tegay, DO, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Jun 29, 2010
 

History

Signs and symptoms of early onset and late-onset Krabbe disease are described below.[5]

Early-onset Krabbe disease (preambulatory) [20, 21, 22]

Stage 1 includes the following:

Stage 2 includes the following:

  • Hyperreflexia
  • Hyporeflexia
  • Opisthotonus
  • Seizures
  • Psychomotor deterioration
  • Optic atrophy
  • Visual loss
  • Sluggish pupillary light response

Stage 3 includes the following:

  • Decerebrate posturing
  • Blindness
  • Deafness

Late-onset Krabbe disease (postambulatory) [18, 19, 23]

Symptoms include the following:

  • Paresthesias
  • Decreased muscle strength
  • Spasticity
  • Ataxia
  • Paresis
  • Psychomotor arrest
  • Psychomotor deterioration
  • Seizures
  • Optic atrophy
  • Visual loss
  • Blindness

Macular cherry red spots were reported in 1 patient. Head circumference may be diminished, although macrocephaly also has been reported.[24]

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Physical

No visceromegaly, dysmorphic features, or skeletal abnormalities are associated with Krabbe disease, nor does the disease cause direct cardiovascular complications. Manifestations of types 1-4 Krabbe disease are as follows:

Type 1

The infantile or classic form accounts for the vast majority of recognized cases (85-90%) and is considered the prototype of Krabbe disease. The clinical course in patients with the infantile form has 3 stages.[1, 5]

Stage 1 includes irritability, hypertonia, hyperesthesia, peripheral neuropathy and arrest of psychomotor development occur following normal early development. Onset usually occurs at age 3-6 months. Feeding difficulties, such as vomiting and reflux, may cause failure to thrive.

In stage 2, rapid psychomotor deterioration, increasing hypertonia, opisthotonus, hyperreflexia, and optic atrophy ensue. Seizures may occur.

In stage 3, severe neurologic impairment often ensues within weeks to months with loss of voluntary movements and persistent decerebrate posturing. Patients become blind, deaf, and unaware of external stimuli. This final stage sometimes is termed the burnt-out stage.

Type 2

Late infantile Krabbe disease follows a similar but less rapid course. After a variable period of normal early development (6 mo to 3 y), the patient develops irritability, hypertonia, ataxia, and psychomotor arrest followed by progressive deterioration and vision loss.

Type 3

Juvenile Krabbe disease is characterized by later age of onset (3-8 y) and greater variability in the tempo of disease progression. Early normal development is followed by a period of rapid psychomotor regression, although the disease then tends to subside into a slower, but progressive, degeneration.

Type 4

Age of onset of adult Krabbe disease varies widely (8 y through adulthood). This type has a more varied clinical symptomatology and course of progression. Patients may present with signs of peripheral neuropathy, cerebellar dysfunction, spasticity, and impaired higher cortical functioning. Patients with type 4 disease may experience a rapid degenerative course or endure an indolent progression.[18, 19]

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Causes

All 4 subtypes are caused by deficient galactosylceramide beta-galactosidase (GALC) activity, which results from mutations to the gene that encodes for the enzyme.[25]

The gene has been mapped to chromosome band 14q31.3[26]

Almost 70 mutations have been identified in the gene responsible for GALC production. Polymorphisms have been identified that may play a considerable role in the resultant phenotypes.[5, 25, 27]

Genotype-phenotype correlations are being delineated to provide a molecular explanation for the clinical variability seen in patients with Krabbe disease.[28]

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Contributor Information and Disclosures
Author

David H Tegay, DO, FACMG  Associate Professor of Medicine and Medical Genetics, New York College of Osteopathic Medicine at the New York Institute of Technology; Assistant Professor of Pediatrics, Stony Brook University Medical Center

David H Tegay, DO, FACMG is a member of the following medical societies: American College of Medical Genetics, American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Osteopathic Association, American Society of Human Genetics, and Federation of American Societies for Experimental Biology

Disclosure: Nothing to disclose.

Coauthor(s)

Rahmat A Balogun  New York College of Osteopathic Medicine at New York Institute of Technology

Rahmat A Balogun is a member of the following medical societies: American Osteopathic Association, Society for Neuroscience, and Student National Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Erawati V Bawle, MD, FAAP, FACMG  Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and American Society of Human Genetics

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.

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics

Disclosure: Nothing to disclose.

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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