Glycogen storage disease type III in Israel: presentation and long-term outcome.

Glycogen storage disease type III (GSD III) was found in the past with an unusual frequency among North African Jews in Israel. The aim of this study was to review the long-term clinical course of GSD III's patients in Israel. Relevant pediatric and adult clinical units of all Israeli hospitals were approached to report on their GSD III patients. 21 (14 M/7F) live patients were located. The average age of the patients was nearly twenty years. Eleven patients were older than 18 years of age. 76% of the patients were of Jewish North African origin, 14% of Jewish European origin, and 10% were Arab Muslims. The symptoms at presentation were fasting, hypoglycemia, hepatomegaly slight hypotonia in infancy and delayed growth. Although in most of the patients their signs and symptoms ameliorated after childhood, significant complications were observed in some 20% of the patients. Consequently, a life long follow up of GSD-III patients is required.

Hyperargininemia: a family with a novel mutation in an unexpected site.

Hyperargininemia is a rare autosomal recessive disorder of the last step of the urea cycle characterized by a deficiency in liver arginase1. Clinically, it differs from other urea cycle defects by a progressive paraparesis of the lower limbs (spasticity and contractures) with hyperreflexia, neurodevelopmental delay and regression in early childhood. Growth is affected as well. Hyperammonemia is episodic, if present at all. The disease is caused by mutations in the ARG1 gene; there are approximately 20 different known ARG1 mutations with considerable genetic heterogeneity. We describe two Arab siblings with a late diagnosis of hyperargininemia and present the genetic findings in their family. As ARG1 sequencing was unrevealing despite suggestive clinical and laboratory findings, molecular cDNA analysis was performed. The ARG1 expression pattern identified a 125-bp out-of-frame insertion between exons 3 and 4, leading to the addition of 41 amino acids and a premature termination codon TGA at the sixth codon downstream. The insertion originated at intron 3 and was attributable to a novel c.305 + 1323 t > c intronic base change that enabled an enhancement phenomenon. This is the first reported exon-splicing-enhancer mutation in patients with hyperargininemia. The clinical course and genetic findings emphasize the possibility that hyperargininemia causes neurological deterioration in children and the importance of analyzing the expression pattern of the candidate gene when sequencing at the DNA level is unrevealing.

Multicenter long-term follow-up of children with idiopathic West syndrome: ACTH versus vigabatrin.

BACKGROUND AND PURPOSE: Long-term follow-up of children with idiopathic West syndrome (WS) treated with adrenocorticotropic hormone (ACTH) or vigabatrin. METHODS: Records of 28 normal magnetic resonance imaging (MRI) WS cases were reviewed for seizure development and cognitive outcome in relation to treatment type and lag. RESULTS: Average age at disease onset was 5.5 months, and average lag time to treatment was 25 days. Fourteen patients were treated with ACTH (eight early and six late), and 14 with vigabatrin (without delay). Response rates were 88% for ACTH and 80% for vigabatrin. Short-term outcomes for seizure cessation and electroencephalography normalization were identical between the groups. In the long-term, early ACTH treatment was better than the rest combined. Average follow-up time was 9 years. A normal cognitive outcome was achieved in 100% of the early-ACTH group, 67% of the late-ACTH group and 54% of the vigabatrin group (P = 0.03). Seizures subsequently developed in 54% of the vigabatrin group, in 33% of the late ACTH group, and 0% of the early ACTH group (P < 0.05). CONCLUSIONS: Idiopathic WS with normal MRI is associated with a good cognitive outcome. Early ACTH treatment, administered within 1 month, yields a better cognitive and seizure outcome than vigabatrin or late ACTH.

Symptoms of migraine in the paediatric population by age group.

The revised criteria of the International Headache Society (IHS) for paediatric headache do not differentiate among age groups. This study aims to determine if different symptoms of migraine are specific or typical of different age groups of children. The files of 160 children (79 boys, 81 girls, mean age 10.39 +/- 3.71 years) with migraine treated at the paediatric headache clinic of a tertiary centre were reviewed. The diagnosis was based on the criteria of the IHS (ICHD-II). The patients were divided by age into three groups according to educational status, < or =6 years (preschool, group 1), >6 to < or =12 years (elementary school, group 2) and >12 to < or =18 years (secondary school, group 3), and compared by symptoms and signs. Symptoms of migraine with and without aura were also compared. There was no significant difference among the groups in rates of unilateral headache, phonophobia, photophobia, awakening pain, nausea or worsening of pain during physical activity. The parameters found to be statistically significant were dizziness and duration of migraine, and aura which increased with time. Frequency of attacks increased with age. The single statistically significant parameter found to be more frequent in younger age was vomiting. The statistically significant parameters of nausea and duration of migraine were more frequent in migraine with aura compared with migraine without aura. In conclusion, most of the migraine symptoms included in the 2004 recommendations of the IHS are not typical for specific paediatric age groups, probably because brain maturity is a continuous process. A familial history of migraine is a frequent finding among all age groups and should be considered in the paediatric criteria, especially in younger children in whom diagnosis is more difficult. Vomiting may help the diagnosis of migraine in young children with a familial history of migraine.

Clinical presentations of mitochondrial cardiomyopathies.

UNLABELLED: To determine the clinical manifestations and interfamilial variability of patients diagnosed with a mitochondrial cardiomyopathy, we reviewed the charts of 14 patients with cardiomyopathy out of 59 patients with mitochondrial disorders who attended the mitochondrial disease clinic at Wolfson Medical Center from 1996 to 2001. All patients underwent a metabolic evaluation including blood lactate, pyruvate, carnitine, and amino acids and urine organic acids. Respiratory chain enzymes were assessed in 10 patients. The mitochondrial DNA (mtDNA) was assessed for mutations. The age at presentation ranged between 6 months and 24 years. Six of the patients died, 5 from heart failure. The cardiomyopathy was hypertrophic in 10 and dilated in 4. Conduction and rhythm abnormalities were present in 6. Eleven patients had family members with mitochondrial disorders. All the patients had additional involvement of one or more systems. Seven patients exhibited a deficiency of a respiratory chain enzyme in the muscle. The MELAS mtDNA point mutation (3243) was found in one patient. Blood lactic acid levels were increased in 5. Brain MRI abnormalities were observed in 4. CONCLUSIONS: Mitochondrial dysfunction frequently affects the heart and may cause both hypertrophic and dilated cardiomyopathy. The cardiomyopathy is usually a part of a multisystem involvement and may rarely be isolated. The course may be stable for many years, but rapid deterioration may occur. Understanding the biochemical and genetic features of these diseases will enable us to comprehend the clinical heterogeneity of these disorders.

Presence of the d8/17 B-cell marker in children with rheumatic fever in Israel.

A genetic predisoposition to rheumatic fever (RF) has been suspected by several researchers. Ten years ago, using monoclonal antibodies, the B-cell alloantigen D8/17 was identified in 90-100% of patients with RF. The aim of the present study was to evaluate whether the marker is found in patients with RF in Israel, where the population is made up of diverse ethnic groups. The Schneider Children's Medical Center in Petah Tikva, Israel, was the setting for this study. The population included 22 children with RF and nine ethnically matched, disease-free individuals who served as controls. Each of the patients and controls were tested for the B-cell antigen with flow cytometry assay by using monoclonal antibodies. The main outcome measure was the difference in the presence of the D8/17 B-cell marker between the patients with RF and the controls. The mean percentage of B-cells expressing the marker was 11.5 +/- 2.9 in the patients and 4.24 +/- 2.7 in the controls (P < 0.001). There was no statistically significant difference in the frequency of the marker by ethnic origin. The present results support earlier studies suggesting that D8/17 is a disease-specific marker with a world-wide distribution which may potentially serve as an additional diagnostic tool in patients with suspected RF.

Skin indurations in response to tuberculin testing in patients with nontuberculous mycobacterial lymphadenitis.

Mantoux results were examined for 29 children with culture-proven nontuberculous mycobacterial lymphadenitis, and 4 species were isolated: Mycobacterium avium-intracellulare complex (from 14 patients [48%]), Mycobacterium haemophilum (from 12 [41%]), Mycobacterium simiae (from 2 [7%]), and Mycobacterium scrofulaceum (from 1 [3%]); the median indurations for each species were 15.5 mm, 14.5 mm, 20 mm, and 23 mm, respectively, and in 17 cases (59%), they were > or =15 mm. In regions with a low incidence of tuberculosis, lymphadenitis thought to be due to nontuberculous mycobacteria should be managed as such, regardless of Mantoux results, thereby avoiding antituberculosis treatment.

The paediatrician and the rabbi.

OBJECTIVES: During recent decades, rabbis in Israel have been playing an increasing role in the consultation of patients or their families on medical issues. The study was performed to determine the attitude of physicians to rabbinical consultation by parents of sick children for purposes of basic medical decision making. DESIGN AND SETTING: A questionnaire was prepared which contained questions regarding physicians' reactions to specific medical situations as well as their demographic data. The study participants included all the available physicians who were employed in the study period at one tertiary medical centre in Israel, which is not associated with any religious organisation. The questionnaire was presented personally to all of the physicians who were available for the study. RESULTS: Between 63% and 77% of the respondents were accepting of rabbinical consultation in regard to medical decisions. Nevertheless, in cases of divergence from accepted medical practice and in emergencies, almost all stated they would take measures to resist the rabbi's advice. This attitude did not correlate with the physician's age, religious status or experience in medicine. CONCLUSIONS: Israeli physicians respect rabbis' suggestions in the area of medical decision making, though they would not let a rabbi's advice interfere with their decisions if they believed the rabbi's opinion went against medical need. In order to prevent an untoward effect of the rabbinical involvement in medicine, rules should be set to establish norms for rabbi-physician collaboration.

Neurologic presentations of mitochondrial disorders.

This article describes the neurologic presentations of children with mitochondrial disorders. The charts of 42 children with highly suspect mitochondrial disorders were reviewed. Thirty-seven children were diagnosed as having definite mitochondrial disorders based on a suggestive clinical presentation and at least one accepted criteria, while in five patients the diagnosis remained probable. All patients had nervous system involvement, but it was the presenting symptom in 28 of 42. Eighteen children had normal intelligence and 24 had mental retardation or developmental delay at the onset of their disease. Twenty-five patients had either an acute regression or a progressive encephalopathy. The most frequent neurologic manifestations were abnormal tone, seizures, extrapyramidal movements, and autonomic dysfunction. The eyes were involved in 11 children. Nerve deafness was found in seven patients. Myopathy was found in only six patients. In conclusion, a complex neurologic picture, especially with other organ involvement, warrants a full mitochondrial evaluation.

Multiple presentation of mitochondrial disorders.

The aim of this study was to assess the heterogeneous clinical presentations of children with mitochondrial disorders evaluated at a metabolic neurogenetic clinic. The charts of 36 children with highly suspected mitochondrial disorders were reviewed. Thirty one children were diagnosed as having a mitochondrial disorder, based on a suggestive clinical presentation and at least one of the accepted laboratory criteria; however, in five children with no laboratory criteria the diagnosis remained probable. All of the patients had nervous system involvement. Twenty seven patients also had dysfunction of other systems: sensory organs in 15 patients, cardiovascular system in five, gastrointestinal system in 20, urinary system in four, haematopoietic system in four, and endocrine system in nine. The clinical presentation was compatible with an established syndrome in only 15 children. Severe lactic acidosis or ragged red muscle fibres were encountered in very few patients. These results suggest that mitochondrial disorders should be evaluated in children presenting with a complex neurological picture or multisystem involvement.

Periventricular brain heterotopias in a child with adrenocortical insufficiency, achalasia, alacrima, and neurologic abnormalities (Allgrove syndrome).

We describe a previously unreported finding of periventricular heterotopias in a brain magnetic resonance imaging (MRI) study, in a girl with adrenocortical insufficiency, alacrima, achalasia, and neurologic deterioration (Allgrove syndrome). This finding could indicate that the underlying mechanism in this syndrome can be traced to the first half of fetal life and also might cause abnormal neuronal migration. This disorder recently has been linked to chromosome 12q13. There could be several explanations for the clinical heterogeneity in this syndrome: a contiguous gene syndrome involving multiple genes, including one whose deletion causes heterotopias, or a deficiency of a gene for a neurotrophic factor active during pre- and postnatal life and responsible for both migration and survival of neurons could be the cause. The identification of the responsible gene(s) will lead to further understanding of this multisystem disorder.

Isolated sphenoidal sinusitis in children.

UNLABELLED: Acute isolated infectious sphenoiditis is an uncommon, potentially dangerous condition which is often misdiagnosed because of its nonspecific symptoms and paucity of clinical signs. We present eight children with isolated sphenoiditis who were managed in our medical centre during the last 2 years and review the literature. All the patients were adolescents or pre-adolescents and all experienced moderate to severe refractory oppressive headache. Four had a history of sinusitis or allergic rhinitis. None had fever or any other directing clinical sign. Diagnosis was made by cranial computer tomography. All were treated with antibiotics and recovered completely without infectious or neurological complications. CONCLUSION: Acute isolated infectious sphenoiditis should be considered in adolescents and pre-adolescents who present with constant moderate to severe oppressive headache. Awareness of this entity will enable early diagnosis and initiation of antibiotic treatment which is essential to avoid complications and surgical intervention.

Optimal detection and identification of Mycobacterium haemophilum in specimens from pediatric patients with cervical lymphadenopathy.

Acid-fast bacilli from pediatric patients with lymphadenopathy were detected in the BACTEC radiometric system and in MB Redox broth, but not on Löwenstein Jensen medium. PCR amplification identified the isolates as Mycobacterium haemophilum, which has special nutrition requirements (iron supplements) for growth. Suitable culture medium ensures optimal recovery of this microorganism, avoiding underdiagnosis.

Conversion reaction: management by the paediatrician.

UNLABELLED: We describe the diagnosis and management of 47 children with conversion reaction seen during the past 9 years in our outpatient department. Some illustrative cases are reported in detail. The study shows that conversion reactions in children can often be accurately diagnosed by detailed history and physical examination. When the diagnosis was made early and presented with certainty, both parental acceptance and the child's recovery were easier, and the need for expensive and unnecessary diagnostic procedures was eliminated. Immediate intervention by the paediatrician prevented perpetuation of the problem, secondary gains and continuing family stress. Most of the patients recovered after a few days without recurrence. The major role of the paediatrician is emphasized. Co-operation between the patients, parents and the paediatrician is important, as is close follow up. CONCLUSION: Paediatricians cope successfully with children with conversion reaction with early diagnosis and immediate intervention.

Efficacy of topical application of eosin compared with zinc oxide paste and corticosteroid cream for diaper dermatitis.

BACKGROUND: Corticosteroids, zinc paste and eosin 2% are well-known topical agents for the treatment of moderate to severe diaper dermatitis. Among these treatments, the aqueous solution of eosin 2% is extensively used in several European countries, but not in the USA or Israel. OBJECTIVE: To assess the therapeutic efficacy of eosin 2% solution compared to the other treatment modalities for diaper dermatitis. METHODS: Fifty-four infants with diaper dermatitis, recruited from hospital wards and community clinics, were randomly assigned to three treatment groups: zinc oxide paste (containing allantoin 0.5%, cod liver oil 17% and zinc oxide 47epercnt;); clobetasone butyrate 0.05%, and aqueous solution of eosin 2%. The severity of the disorder was graded on a 6-point scale by observation and quantitative measurement of the lesions. The groups were compared for rates and time to heal. Due to the red color of eosin, a double-blind controlled study was impossible. RESULTS: Following 5 days of treatment, the rate of complete healing in the group treated with eosin (61%) was significantly higher (p = 0.0479) than that in the zinc oxide paste and corticosteroid groups (22 and 33%, respectively). Furthermore, in cases of partial healing, the degree of improvement was higher in the eosin group than the other two (p = 0.0205). The fastest improvement was observed in the group treated with corticosteroid cream. CONCLUSION: Considering the potential hazards of topical corticosteroids and the greater overall efficacy of eosin 2% solution, we suggest that eosin is the preferred treatment for diaper dermatitis.

Preoperative localization of a foreign body by magnetic resonance imaging.

Nonradioopaque foreign bodies are very difficult to detect and localize. A case is presented in which a retained palm tree thorn was visualized and extracted with the help of magnetic resonance imaging.

Tietze's syndrome in children and infants.

Tietze's syndrome, characterized by isolated swelling and tenderness of a costochondral junction, usually occurs in adults. We describe eight cases of Tietze's syndrome in children, four of them aged 1 year or less. The clinical aspects and laboratory and imaging findings should enable the clinician to recognize this benign entity, thereby avoiding invasive diagnostic procedures to rule out other conditions.