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Medulloblastoma in young children has a poor prognosis. Furthermore, cognitive function in survivors is often impaired owing to treatment with cranial radiotherapy. This study obtained promising results in children undergoing intensive chemotherapy alone. For years there has been little progress in the treatment of medulloblastoma, the commonest tumor of the central nervous system in children. This study obtained promising results in children undergoing intensive chemotherapy alone. Twenty-five to 35 percent of cases of medulloblastoma, the most common malignant brain tumor of childhood, occur in children younger than three years of age. 1 In contrast to the prognosis for older children, the prognosis for infants and young children treated with surgery, radiotherapy, and chemotherapy remains poor: survival rates have been static for two decades. 2 The lack of progress relates not only to the frequent occurrence of metastases at diagnosis but also to the biology of medulloblastoma in young children. 3 – 5 In addition, the susceptibility of the immature brain to radiotherapy-induced cognitive deficits, 6 – 8 which increase for years after . . .

Young children with brain tumours are at high risk of developing treatment-related sequelae. We aimed to assess neuropsychological outcomes 5 years after treatment. This cross-sectional study included children under 4 years of age with medulloblastoma (MB) or ependymoma (EP) enrolled in the German brain tumour trials HIT2000 and HIT-REZ2005. Testing was performed using the validated Wuerzburg Intelligence Diagnostics (WUEP-D), which includes Kaufman-Assessment-Battery, Coloured Progressive Matrices, Visual-Motor Integration, finger tapping \"Speed\", and the Continuous Performance Test. Of 104 patients in 47 centres, 72 were eligible for analyses. We assessed whether IQ was impacted by disease extent, disease location, patient age, gender, age at surgery, and treatment (chemotherapy with our without craniospinal irradiation [CSI] or local radiotherapy [LRT]). Median age at surgery was 2.3 years. Testing was performed at a median of 4.9 years after surgery. Patients with infratentorial EPs (treated with LRT) scored highest in fluid intelligence (CPM 100.9±16.9, mean±SD); second best scores were achieved by patients with MB without metastasis treated with chemotherapy alone (CPM 93.9±13.2), followed by patients with supratentorial EPs treated with LRT. In contrast, lowest scores were achieved by patients that received chemotherapy and CSI, which included children with metastasised MB and those with relapsed MB M0 (CPM 71.7±8.0 and 73.2±21.8, respectively). Fine motor skills were reduced in all groups. Multivariable analysis revealed that type of treatment had an impact on IQ, but essentially not age at surgery, time since surgery or gender. Our results confirm previous reports on the detrimental effects of CSI in a larger cohort of children. Comparable IQ scores in children with MB treated only with chemotherapy and in children with EP suggest that this treatment strategy represents an attractive option for children who have a high chance to avoid application of CSI. Longitudinal follow-up examinations are warranted to assess long-term neuropsychological outcomes.

To the Editor: In the report by Rutkowski et al. (March 10 issue) 1 regarding treatment of early childhood medulloblastoma with postoperative chemotherapy alone, 20 of 43 children under the age of three years (46.5 percent) had desmoplastic medulloblastoma, and these 20 children had a five-year progression-free survival rate of 85 percent. The desmoplastic variant is considered to be less aggressive than classic medulloblastoma and occurs mainly in adolescents and adults. 2 , 3 As far as we know, desmoplastic histologic features are not found in a large proportion of children who are younger than three years of age. Could the somewhat higher-than-expected . . .

Classical galactosemia, characterized clinically by acute hepatic dysfunction, sepsis, cataract, and failure to thrive, is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT). Galactose restriction normalizes these acute symptoms; however, long-term complications such as intellectual deficits and ovarian failure are conspicuous in the majority of patients. Here we report two Turkish siblings with classical galactosemia. The clinical course of the two children differed markedly: only the older girl suffered from severe acute symptoms during the neonatal period, and she developed greater mental retardation than her younger affected brother. The functional activity of GALT was virtually absent in each affected children. The mother and two healthy siblings exhibited approximately 50% normal GALT activity and the father approximately 25%. Molecular analysis revealed that these two galactosemic siblings were homozygous for a stop codon mutation of E340X in GALT exon 10. Moreover, two additional mutations, a neutral polymorphism L218L and N314D, which are typical for the Duarte-I variant, were found in the same GALT allele. The two healthy siblings and the parents were heterozygous for these combinations of mutations. In addition, the father's second GALT allele revealed three intron mutations at nucleotide position 1105 (G-->C), 1323 (G-->A) and 1391 (G-->A) and the N314D mutation, which correspond to the mutations of Duarte-2 variant. Our findings indicate that in classical galactosemia several distinct mutations can be present in one allele (in cis) of the GALT gene. Therefore it seems to be necessary to examine all introns and exons of the GALT gene in galactosemic patients who do not carry the Q188R mutation or another frequent mutation in the GALT gene.