Newborn screening for Krabbe disease in New York State: the first eight years' experience.

Purpose: Krabbe disease (KD) results from galactocerebrosidase (GALC) deficiency. Infantile KD symptoms include irritability, progressive stiffness, developmental delay, and death. The only potential treatment is hematopoietic stem cell transplantation.

Neurocognitive and neuroradiologic central nervous system late effects in children treated on Pediatric Oncology Group (POG) P9605 (standard risk) and P9201 (lesser risk) acute lymphoblastic leukemia protocols (ACCL0131): a methotrexate consequence? A report from the Children's Oncology Group.

Concerns about long-term methotrexate (MTX) neurotoxicity in the 1990s led to modifications in intrathecal (IT) therapy, leucovorin rescue, and frequency of systemic MTX administration in children with acute lymphoblastic leukemia. In this study, neurocognitive outcomes and neuroradiologic evidence of leukoencephalopathy were compared in children treated with intense central nervous system (CNS)-directed therapy (P9605) versus those receiving fewer CNS-directed treatment days during intensive consolidation (P9201). A total of 66 children from 16 Pediatric Oncology Group institutions with "standard-risk" acute lymphoblastic leukemia, 1.

Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34.

Background: The randomized controlled Pediatric Oncology Group study 9233 tested the hypothesis that dose-intensive (DI) chemotherapy would improve event-free survival (EFS) for children <3 years of age with newly diagnosed malignant brain tumors.

Methods: Of 328 enrolled eligible patients, diagnoses were medulloblastoma (n = 112), ependymoma (n = 82), supratentorial primitive neuroectodermal tumor (sPNET, n = 38) and other malignant brain tumors (n = 96), and were randomized to 72 weeks of standard dose chemotherapy (Regimen A, n = 162) or DI chemotherapy (Regimen B, n = 166). Radiation therapy (RT) was recommended for patients with evidence of disease at completion of chemotherapy or who relapsed within 6 months of chemotherapy completion.

Patterns of magnetic resonance imaging abnormalities in symptomatic patients with Krabbe disease correspond to phenotype.

Background: Initial magnetic resonance imaging studies of individuals with Krabbe disease were analyzed to determine whether the pattern of abnormalities corresponded to the phenotype.

Methods: This was a retrospective, nonblinded study. Families/patients diagnosed with Krabbe disease submitted medical records and magnetic resonance imaging discs for central review.

Lifetime risk estimators in epidemiological studies of Krabbe Disease: Review and Monte Carlo comparison.

This review addresses difficulties arising in estimating epidemiological parameters of leukodystrophies and lysosomal storage disorders, with special focus on Krabbe disease. Although multiple epidemiological studies of Krabbe disease have been published, these studies are difficult to reconcile since they have used different study populations and varying methods of calculation. Confusion exists regarding which epidemiological parameters have been estimated; the current review shows that most previous estimates can be properly interpreted as lifetime risk at birth.

Does galactocerebrosidase activity predict Krabbe phenotype?

This study sought to determine whether galactocerebrosidase activity is predictive of Krabbe onset age, or of survival from onset when controlling for age at onset of signs. We analyzed data on 55 symptomatic patients from the Hunter James Kelly Research Institute's World-Wide Registry. They were tested for galactocerebrosidase activity at Jefferson Medical College (Philadelphia, PA), using survival models in a path model context.

Death rates in the U.S. due to Krabbe disease and related leukodystrophy and lysosomal storage diseases.

Leukodystrophies (LD) and lysosomal storage disorders (LSD) have generated increased interest recently as targets for newborn screening programs. Accurate epidemiological benchmarks are needed in the U.S.

Induction chemotherapy and conformal radiation therapy for very young children with nonmetastatic medulloblastoma: Children's Oncology Group study P9934.

Purpose: P9934 was a prospective trial of systemic chemotherapy, second surgery, and conformal radiation therapy (CRT) limited to the posterior fossa and primary site for children between 8 months and 3 years old with nonmetastatic medulloblastoma. The study was open from June 2000 until June 2006.

Patients And Methods: After initial surgery, children received four cycles of induction chemotherapy, followed by age- and response-adjusted CRT to the posterior fossa (18 or 23.

Array CGH improves detection of mutations in the GALC gene associated with Krabbe disease.

Background: Krabbe disease is an autosomal recessive lysosomal storage disorder caused by mutations in the GALC gene. The most common mutation in the Caucasian population is a 30-kb deletion of exons 11 through 17. There are few other reports of intragenic GALC deletions or duplications, due in part to difficulties detecting them.

Later onset phenotypes of Krabbe disease: results of the world-wide registry.

The majority of newborns screening positive for Krabbe disease have not exhibited the expected early infantile phenotype, with most clinically normal despite low galactocerebrosidase activity and two mutations. Most are expected to develop the later onset phenotypes. The World-Wide Krabbe Registry was developed in part to expand our understanding of the natural history of these rare variants.

Developmental and functional outcomes in children with a positive newborn screen for Krabbe disease: a pilot study of a phone-based interview surveillance technique.

Objective: To assess the utility of a telephone-based interview system in providing ongoing monitoring of the developmental and functional status of children with both positive newborn screens for Krabbe disease and low galactocerebrosidase activity on confirmatory testing, and to determine whether this approach provides improved compliance with follow-up compared with formal neuropsychological testing.

Study Design: Infants with low galactocerebrosidase activity (as detected by the New York State newborn screening program) were eligible for this longitudinal prospective cohort study. Consenting families were interviewed by telephone at infant ages of 4, 8, 12, 18, and 24 months.

Early infantile Krabbe disease: results of the World-Wide Krabbe Registry.

New York State began screening for Krabbe disease in 2006 to identify infants with Krabbe disease before symptom onset. Because neither galactocerebrosidase activity nor most genotypes reliably predict phenotype, the World Wide Registry was developed to determine whether other clinical/neurodiagnostic data could predict early infantile Krabbe disease in the newborn screening population. Data on disease course, galactocerebrosidase activity, DNA mutations, and initial neurodiagnostic studies in 67 symptomatic children with early infantile Krabbe disease were obtained from parent questionnaires and medical records.

Utility of cerebrospinal fluid cytology in newly diagnosed childhood ependymoma.

The role of cytology of cerebrospinal fluid (CSF) has not been established in pediatric ependymoma. Thirty-two children with metastatic ependymoma were analyzed: 11 patients had only positive CSF cytology, 6 had only positive magnetic resonance imaging (MRI) findings, and 15 had both CSF cytology and MRI positive. Twenty-two patients relapsed.

Risk factors for cognitive decline in children treated for brain tumors.

The long term effects of central nervous system therapy for children with brain tumors have been the subject of research since the 1970s. Many studies have demonstrated that children treated for brain tumors with surgery and standard radiation therapy have developed intellectual decline which is progressive over at least a decade. Risk factors for this cognitive deterioration have been identified and include perioperative complications, possibly hydrocephalus, high radiation dose, large volume radiation, chemotherapy (especially methotrexate), radiation vasculopathy and young age at the time of treatment.

The long-term outcomes of presymptomatic infants transplanted for Krabbe disease: report of the workshop held on July 11 and 12, 2008, Holiday Valley, New York.

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive disorder of white matter resulting from deficiency of galactosylceramide beta-galactosidase (GALC) and the consequent accumulation of galactosylceramide and psychosine. Although most patients present within the first 6 months of life, i.e.

Newborn screening for Krabbe disease: the New York State model.

Krabbe disease is a rare inherited neurologic disorder affecting the central and peripheral nervous systems. The disease has four phenotypes: early infantile, later onset, adolescent, and adult. The only known treatment is hematopoietic stem cell transplantation, which is, in the early infantile form of the disease, most beneficial if performed before onset of clinical symptoms.

The Hunter's Hope Krabbe family database.

The objective was to identify presenting signs and symptoms, age at onset of symptoms and diagnosis, and survival in a large population of children with Krabbe disease. In 1997, Hunter's Hope Foundation began collecting clinical data on patients who had been diagnosed with Krabbe disease. As of June 2006, 334 families had returned questionnaires.

Diagnosis of brain tumors in children.

Brain tumors are the most common solid tumor of childhood. The presenting signs and symptoms reflect the nature and location of the tumor, the presence of increased intracranial pressure, and the age and development of the child. A detailed history and neurologic examination will, in most cases, identify children with intracranial neoplasms.