Krabbe Disease: A Case Report Nicole Keller D.O., Alison Chase D.O. Department of Pediatrics, Advocate Hope Children’s Hospital Krabbe Disease: A Case Report Nicole Keller D.O., Alison Chase D.O. Department of Pediatrics, Advocate Hope Children’s Hospital 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. 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 1 st cousins. Developmental History: supports head, reaches for objects, smiled/laughed at 2 months. At 3 ½ months noted regression in these milestones. Medications: zantac, nystatin Admission physical exam: Weight & height <3%, Head circumference 20% Anterior fontanel closed Irritable, poorly consolable Limited visual tracking Hypertonia, poor head/trunk control 1.Levy PA. Inborn errors of metabolism. Pediatrics in Review 2009; 30: Escolar ML, et al. Transplantation of umbilical-cord blood in babies with infantile krabbe’s disease. New England Journal of Medicine 352 (20): May Kliegman, et al. Nelson textbook of Pediatrics. Elsevier 2007; Roberts G, Palfrey JS, Bridgemohan C. The medical evaluation of a child with developmental delay. Contemporary Pediatrics March 5.Rudolph AM, Kamei RK, Overby JK. Rudolph’s fundamentals of pediatrics. McGraw-Hill 2002; 6-12, Introduction and Significance of case: Conclusion/Implications: References: Patient Description: CSF: high protein CT brain: calcifications, atrophy Confirmatory testing: molecular analysis showing low GALC enzyme activity Evaluation of Developmental Delay Differential Diagnosis: Irritability, Failure to Thrive and/or Developmental Regression : Pathophysiology: 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. 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.  Metabolic: inborn errors of metabolism, toxins  Neuro: hydrocephalus, tumor, bleeding, infection, seizures, HIE  Endocrine: thyroid disorders, growth hormone deficiency  Genetic: syndromes  Social: inappropriate intake, abuse/neglect Intervention: 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. 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 DeschDr. Larry Roy Acknowledgements: Results: Diagnosis:  Labs/imaging to evaluate inborn errors of metabolism:  MRI/CT of brain  Plasma amino acids  Urine organic acids  CSF studies  pH  Lactate  Ammonia  Verify newborn screen  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. 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.