Liora Kornreich

Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients.

Abstract:  Objective: Previous studies suggested that in patients with thalassemia major, initiating deferoxamine (DFO) therapy before puberty can prevent iron‐induced failure of growth and puberty. However, early initiation of chelation has also been associated with DFO toxicity. The aim of this retrospective study was to determine the prevalence rates of endocrine complications and DFO bone toxicity in our thalassemia major patients and to correlate them with the degree of iron chelation. Methods: Thirty‐nine patients with thalassemia major were followed for a median of 16.3 yr (range 2–28). Individual mean serum ferritin level during the study period was calculated using repeated annual measurements. Bone DFO toxicity was assessed by wrist and spine radiographs; endocrine dysfunction by anthropometric measurements and pubertal stage; and hypogonadotropic hypogonadism by lack of luteinizing hormone response to gonadotropin‐releasing hormone. Results: Chelation therapy was initiated at median age 4.9 yr. Mean serum ferritin level during the study period was 2698 ± 1444 ng/mL. Hypogonadism was noted in 59% of the patients who reached pubertal age, and short stature was found in 36% of patients who reached final height. Mean ferritin level of 2500 ng/mL during puberty was the cut‐off for hypogonadism, and ferritin level of 3000 ng/mL during prepuberty was the cut‐off for final short stature. None of the patients who attained final height had signs of DFO bone toxicity. Conclusions: High serum ferritin levels during puberty are a risk factor for hypogonadism, and high serum ferritin levels during the first decade of life predict final short stature. It remains to be determined whether improving chelation by earlier initiation of DFO or by the combined use of DFO and deferiprone will lead to better growth and sexual development without DFO toxicity.

Invasive fungal infections in pediatric oncology

Data on the epidemiology and outcome of invasive fungal infections in children with cancer are limited. The aim of the study was to delineate the epidemiologic, clinical features, risk factors, and outcome of invasive fungal infections in this population.

Methotrexate treatment protocols and the central nervous system: significant cure with significant neurotoxicity.

Methotrexate can influence the central nervous system through several metabolic toxic pathways. These effects can be categorized as immediate, acute to subacute, or chronic neurologic syndromes. The acute to subacute syndrome occurs frequently in acute lymphoblastic leukemia treatment protocols, generally manifesting with focal neurologic signs and changes seen on magnetic resonance imaging and single photon emission computed tomography. While in some patients the neurotoxicity is transient and benign and allows for continuation of chemotherapy, in others it can be quite severe and debilitating, leading to permanent neurologic deficits. The need to modify the treatment protocols when neurotoxicity appears is not fully established. It is also unknown whether the use of sufficient amounts of leucovorin can overcome the toxic effects of the drug. (J Child Neurol 2000;15:573-580).

High incidence of meningioma in cranial irradiated survivors of childhood acute lymphoblastic leukemia

Most survivors of childhood acute lymphoblastic leukemia (ALL) and T‐cell lymphoma (T‐NHL) treated before 1990 received cranial radiation. This study assessed the occurrence of second tumors in irradiated and non‐irradiated survivors.

Central precocious puberty: Evaluation by neuroimaging

To evaluate the incidence of abnormal intracranial findings in children with central precocious puberty, 62 children (51 girls, 11 boys) were examined by computerized tomography and/or magnetic resonance imaging (MRI) of the brain. Forty-four had normal examinations; 18 (11 girls, 7 boys) showed intracranial pathologies, including hamartoma of the tuber cinereum (8 cases), parenchymal loss (3 cases), hypothalamicchiasmatic lesions (2 cases), lesions of the corpus callosum (2 cases), suprasellar cyst (1 case), and pineal cyst and mesiotemporal sclerosis (1 case each). Based on the correlation between the clinical and the imaging results of this series, the authors recommend MRI as the imaging method of choice in the investigation of precocious puberty.

Complications of Mastoiditis in Children at the Onset of a New Millennium

The aim of the present study was to review our recent experience in the diagnosis and treatment of acute mastoiditis and its complications in a single tertiary-care, university-affiliated pediatric center. Ninety-eight children with 101 episodes of acute mastoiditis were included in the study. The mean interval from onset of illness to mastoiditis was 4.5 days. Ear cultures most often grew Streptococcus pneumoniae and Pseudomonas aeruginosa (23.7% each). Complications occurred in 15.8% of episodes. The only factor differentiating children with and without complications was white blood cell count. These findings indicate that acute mastoiditis not only is a complication of prolonged infection of the middle ear, but may also present as an acute infection of the mastoid bone that can progress within 48 hours. The complication rate remains high, and antibiotic treatment at the onset of symptoms does not prevent complications. A high white blood cell count on admission may serve as a predictive factor of complicated cases.

Iron overload following bone marrow transplantation in children : MR findings

Objective. The purpose of this study was to determine the incidence of post-transfusional iron overload in children after bone marrow transplantation by reviewing their magnetic resonance imaging (MR) findings. Materials and methods. We reviewed the abdominal MR studies of 13 children after autologous bone marrow transplantation. Nine of the children had also undergone MR prior to transplantation. Iron deposition in the liver, spleen and bone marrow was graded semi-quantitatively on both T1- and T2-weighted images. Serum ferritin levels and number of blood units given after bone marrow transplantation were recorded. Results. None of the pre-transplantation MR studies revealed iron overload. After bone marrow transplantation, three children showed normal liver and spleen. Iron overload in the liver was noted in ten patients (77 %), six of whom also showed iron overload in the spleen (46 %) and five in the bone marrow (38.5 %). The degree of hepatic iron overload was correlated significantly and splenic iron overload was correlated weakly with the number of blood transfusions (P = 0.01 and P > 0.01, respectively), but neither was correlated with the serum ferritin level. Conclusion. Iron overload commonly accompanies bone marrow transplantation. The observed pattern of iron deposition, in which the spleen was uninvolved in 40 % of patients demonstrating iron overload, is not typical of post-transfusional hemochromatosis.

Biallelic SZT2 Mutations Cause Infantile Encephalopathy with Epilepsy and Dysmorphic Corpus Callosum

Epileptic encephalopathies are genetically heterogeneous severe disorders in which epileptic activity contributes to neurological deterioration. We studied two unrelated children presenting with a distinctive early-onset epileptic encephalopathy characterized by refractory epilepsy and absent developmental milestones, as well as thick and short corpus callosum and persistent cavum septum pellucidum on brain MRI. Using whole-exome sequencing, we identified biallelic mutations in seizure threshold 2 (SZT2) in both affected children. The causative mutations include a homozygous nonsense mutation and a nonsense mutation together with an exonic splice-site mutation in a compound-heterozygous state. The latter mutation leads to exon skipping and premature termination of translation, as shown by RT-PCR in blood RNA of the affected boy. Thus, all three mutations are predicted to result in nonsense-mediated mRNA decay and/or premature protein truncation and thereby loss of SZT2 function. Although the molecular role of the peroxisomal protein SZT2 in neuronal excitability and brain development remains to be defined, Szt2 has been shown to influence seizure threshold and epileptogenesis in mice, consistent with our findings in humans. We conclude that mutations in SZT2 cause a severe type of autosomal-recessive infantile encephalopathy with intractable seizures and distinct neuroradiological anomalies.

Osteopathia striata, cranial sclerosis with cleft palate and facial nerve palsy

Osteopathia striata (OS) is a rare bone dysplasia characterized by longitudinal sclerotic striations of the long bones. It is of no clinical importance, but OS associated with cranial sclerosis represents a separate entity with a high incidence of palatine malformations and deafness. Only 19 cases of this entity have been reported in the literature. One patient of this series also had facial nerve paralysis. This paper presents a second case of OS, cranial sclerosis, palatine pathology and recurrent facial nerve paralysis. This incidence of 2/20 (10%) does not seem to be coincidental but raises the possibility that facial nerve palsy is one of the clinical manifestations of this specific bone abnormality.

Task Switching After Cerebellar Damage

The authors of this study investigated task switching following cerebellar damage. The study group consisted of 7 children and adolescents (M age=13.8 years) who underwent surgical removal of a benign posterior fossa tumor. They were tested at a sufficient interval after surgery (M lag=6.13 years) for restoration of normal cognitive skills and intelligence. Although all showed normal learning of the task compared with control participants, when rapid behavioral changes were required (short preparation time), they exhibited behavioral rigidity manifested by enhanced switching cost. These results are in line with another study on serial reaction time with the same patients (A. Berger et al., in press). They have important implications for our understanding of the cognitive sequelae of early cerebellar damage as well as the involvement of the cerebellum in task switching.