Transcript C-25_Keller - Advocatehealth.com

Krabbe Disease: A Case Report
Nicole Keller D.O., Alison Chase D.O.
Department of Pediatrics, Advocate Hope Children’s Hospital
Introduction and
Significance of case:
Diagnosing a child with an inborn error of
metabolism, especially one with a chronic
presentation like Krabbe disease requires a
high index of suspicion. Often these children
have been misdiagnosed with several
conditions before diagnosis is made. Due to
their rarity, it is not likely for a physician to
encounter most of these disorders. The
importance of recognizing the symptoms and
understanding the prognosis of Krabbe
disease is important when evaluating a
child. The only treatment available to these
patients is stem cell transplant, which must
be undertaken before symptoms onset in the
first few months of life, to have any positive
effect on survival and/or quality of
life. Therefore, early diagnosis is imperative.
Patient Description:
Chief
complaint: 5 month old female with
failure to thrive, irritability, hypertonia, and
developmental regression.
Past
Medical History: GERD, thrush; at 4 mo
hospitalized for irritability, fever, and poor PO.
Social
History: Arabic. Father resides in Yemen
and had no contact with child. No travel history.
Family
History: parents are 1st cousins.
Developmental
History:
supports
head,
reaches for objects, smiled/laughed at 2
months. At 3 ½ months noted regression in
these milestones.
Medications:
Admission

zantac, nystatin
physical exam:
Weight
&
height
circumference 20%

Anterior fontanel closed

Irritable, poorly consolable
<3%,
Head

Limited visual tracking

Hypertonia, poor head/trunk control
Differential Diagnosis:
Diagnosis:
Intervention:
Irritability, Failure to Thrive
and/or Developmental
Regression:
 Labs/imaging to evaluate inborn errors of
metabolism:
Currently, there is no treatment available for
patients that present with advanced symptoms,
and it is difficult to predict severity. Intravenous
enzyme is ineffective in treating metabolic
diseases affecting the central nervous system,
because of its inability to cross the blood-brain
barrier. Therefore, most patents have poor
prognosis. If diagnosis is made earlier in an
asymptomatic patient, hematopoietic stem-cell
transplantation can be done. Donor leukocytes
transfer of deficient enzyme allowing for for
possible
survival
and
preservation
of
developmental skills.
 MRI/CT of brain
 Plasma amino acids
 Urine organic acids
 Metabolic: inborn errors of metabolism,
toxins
 CSF studies
 Neuro: hydrocephalus, tumor, bleeding,
infection, seizures, HIE
 Lactate
 Endocrine: thyroid disorders, growth
hormone deficiency
 Verify newborn screen
 pH
 Ammonia
 Genetic: syndromes
Results:
 Social: inappropriate intake, abuse/neglect
• CSF: high protein
• CT brain: calcifications, atrophy
Evaluation of Developmental Delay
• Confirmatory testing: molecular analysis
showing low GALC enzyme activity
Pathophysiology:
Krabbe disease is an autosomal recessive
inborn error of metabolism affecting in
1/100,000 live births. Leukodystrophies, such as
Krabbe disease, are disorders of enzyme
deficiency
resulting
in
progressive
accumulation of an intermediate, which
leads
to
cellular
damage
causing
degeneration of the central nervous system.
Galactocerebrosidase is deficient in Krabbe
disease; an enzyme normally found in high
concentrations
in
the
myelin
sheaths
surrounding nerves. This causes build-up of
galactosylsphingosine (psychosine), which then
leads to destruction of oligodendroglia
resulting in demyelination and subsequent
neurologic findings such as poor tone, inability
to feed, spasticity, irritability and developmental
regression.
In children, the peak period
of myelin formation and
turnover is in the first 18
months of life. This helps
explain
why
symptoms
typically occur during this
time.
Our patient presented with neurologic symptoms
of the disease, therefore was not a candidate for
stem cell transplant. She was given supportive
care, and ultimately passed away at 16 months
of age.
Family members were counseled regarding the
genetic implication of the disease and it’s
prognosis. Most children die by age 2-3 years
old due to respiratory complications.
Conclusion/Implications:
Krabbe disease should be considered when a
patient presents with developmental regression,
failure to thrive and irritability
Diagnosis is made ultimately by detecting
enzyme deficiency.
Work up of metabolic
conditions should include: complete metabolic
panel,
blood
gas,
lactate,
ammonia,
urine/plasma amino and organic acids.
Stem cell transplantation is the only curative
treatment available, and requires early
diagnosis and initiation prior to symptom onset.
Besides cases with family history, due to the
rarity it is not likely to be suspected within
timeframe except if included in the newborn
screening.
Acknowledgements:
Thank you to the following physicians who helped in the care, diagnosis and treatment of our patient. Also,
a special thank you to those who helped make this case report possible:
Dr. Lydia Jazmines
Dr. Sonali Mehta
Dr. Larry Desch
Dr. Larry Roy
References:
1.Levy PA. Inborn errors of metabolism. Pediatrics in Review 2009; 30: 131-137.
2.Escolar ML, et al. Transplantation of umbilical-cord blood in babies with infantile krabbe’s disease. New England
Journal of Medicine 352 (20): 2069-81. 2005 May 19.
3.Kliegman, et al. Nelson textbook of Pediatrics. Elsevier 2007; 527-669
4.Roberts G, Palfrey JS, Bridgemohan C.
Contemporary Pediatrics. 2004 March
The medical evaluation of a child with developmental delay.
5.Rudolph AM, Kamei RK, Overby JK. Rudolph’s fundamentals of pediatrics. McGraw-Hill 2002; 6-12, 221-252.