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Background: Glutamine has been shown to acutely decrease whole-body protein degradation in Duchenne muscular dystrophy (DMD)., Objective: To improve nutritional support in DMD, we tested whether oral supplementation with glutamine for 10 d decreased whole-body protein degradation significantly more than did an isonitrogenous amino acid control mixture., Design: Twenty-six boys with DMD were included in this randomized, double-blind parallel study; they received an oral supplement of either glutamine (0.5 g . kg(-1) . d(-1)) or an isonitrogenous, nonspecific amino acid mixture (0.8 g . kg(-1) . d(-1)) for 10 d. The subjects in each group were not clinically different at entry. Leucine and glutamine metabolisms were estimated in the postabsorptive state by using a primed continuous intravenous infusion of [1-(13)C]leucine and [2-(15)N]glutamine before and 10 d after supplementation., Results: A significant effect of time was observed on estimates of whole-body protein degradation. A significant (P < 0.05) decrease in the rate of leucine appearance (an index of whole-body protein degradation) was observed after both glutamine and isonitrogenous amino acid supplementation [x +/-SEM: 136 +/- 9 to 124 +/- 6 micromol . kg fat-free mass (FFM)(-1) . h(-1) for glutamine and 136 +/- 6 to 131 +/- 8 micromol . kg FFM(-1) . h(-1) for amino acids]. A significant (P < 0.05) decrease in endogenous glutamine due to protein breakdown was also observed (91 +/- 6 to 83 +/- 4 micromol . kg FFM(-1) . h(-1) for glutamine and 91 +/- 4 to 88 +/- 5 micromol . kg FFM(-1) . h(-1) for amino acids). The decrease in the estimates of whole-body protein degradation did not differ significantly between the 2 supplemental groups., Conclusion: Oral glutamine or amino acid supplementation over 10 d equally inhibits whole-body protein degradation in DMD.

We report the observation of an 18-year-old girl, whose clinical presentation was very suggestive of a congenital myopathy with neonatal onset. A congenital myopathy had been already diagnosed in her brother and in addition her half-cousin died diagnosed with a severe nemaline myopathy at age 4 years. A muscle biopsy performed on both siblings revealed histological and ultrastructural features of 'cap myopathy'. This case report suggests that 'cap myopathy' and some cases of nemaline myopathy with neonatal onset might be two phenotypic expressions of the same genetic disorder. These two entities could therefore, perhaps, be regarded as 'Z-line disorders' possibly caused by defective myofibrillogenesis.

Background: Duchenne muscular dystrophy (DMD) is often associated with obesity, which worsens the handicap early in the course of the disease. Nutritional assessment, however, can be difficult and often misleading in DMD., Objective: Two methods of estimating body composition in DMD, skinfold-thickness (ST) measurement and bioelectrical impedance analysis (BIA), were compared with a reference method, labeled water dilution (WD)., Design: Body composition was estimated by using ST measurements and BIA (50 kHz, 800 mAmp), as well as the WD method (1 mL H2(18)O/kg) in 11 DMD patients with a mean (+/-SD) age of 10.0 +/- 2.5 y., Results: When compared with the WD method, ST measurement significantly (P < 0.01) overestimated fat-free mass (FFM) (mean +/- SD ST: 24.5 +/- 5.9 kg; mean +/- SD WD: 18.2 +/- 2.5 kg), which led to an underestimation of the percentage of fat mass (%FM) (ST: 23.3 +/- 10.4%; WD: 40.1 +/- 17.1%; P < 0.05). In contrast, estimates obtained with BIA (FFM: 21.5 +/- 4.5 kg; %FM: 31.3 +/- 13.9%) did not differ from those obtained with WD. The difference from the reference method was less for BIA (mean: 3.3 kg; 95% CI: 0.8, 4.9 kg) than for ST (6.3 kg; 2.2, 8.6 kg). WD and BIA defined 73% and 55%, respectively, of the children as obese (%FM associated with body mass index cutoffs for obesity), whereas ST measurements defined 9% as obese (P < 0.01)., Conclusions: Body-composition estimates by BIA are closer to those by WD than are those by ST measurement. Early detection of fat accumulation and longitudinal monitoring of nutritional care are 2 relevant applications of BIA to prevent obesity and hence lessen the burden of DMD.

Autism is defined by 3 main criteria: disturbance of reciprocal social interaction, disturbance of communication (including language comprehension and spoken language) and disturbance of normal variation in behaviour and imaginative activities; an onset before age 36 months is also required. The neuropediatric contribution to autism is dominated by the search for an underlying organic etiology, especially if there are arguments for an associated encephalopathy: ante- or perinatal medical history, dysmorphic signs, skin spots, neurological abnormalities, somatic abnormalities compatible with a neurometabolic disorder. The main associated conditions with autism are: chromosome anomalies, monogenic syndrome (including fragile X syndrome), neurocutaneous syndromes, epileptic encephalopathies, neurometabolic diseases, and dystrophinopathies. The identification of an associated medical condition to autism is primordial in prospect of genetic counselling, and by the change induced in familial perception of autism.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterised by motoneuron degeneration in the anterior horn of the spinal cord and in the bulbar nuclei. The various types of SMA are linked to the 5q13 locus in 95 % of cases. In the absence of an effective specific treatment, orthopaedic and respiratory management can significantly improve the prognosis. To study the contemporary natural history of SMA and to identify clinical and non invasive prognostic criteria, 168 patients with SMA were recruited in 6 hospital units (Lille, Lyon, Marseille, Paris) during a 4-year prospective multicenter follow-up study (1998-2002). Follow-up has now lasted at least 4 years in 151 cases (90%), and 24 of these patients have died Disease outcome was appraised by using three criteria: muscle strength, the sum of the motor function and examination index (IFM), the respiratory muscle paralysis index (IMR), and the dorsal decubitus forced vital capacity/theoretical index (ICV/CT). Statistical analysis showed a significant worsening (about 20%) of the three criteria during follow-up. The motor function and examination index (IFM) is particularly interesting: the difference between initial and final status was significant in all age groups and in all three types of the disease. The IFM may thus be useful as the main outcome measure during therapeutic trials.

Introduction: Niemann-Pick Type C disease (NPC) is an autosomal recessive neurovisceral lysosomal lipid storage disorder., Case Report: A 31-year-old right-handed woman had suffered from schizophrenia for 13 years. At 25 years of age, she developed a gait disorder with a static and kinetic cerebellar syndrome, dysarthria, vertical supranuclear gaze palsy and cognitive impairment. Brain MRI was normal. Abdominal ultrasonography was performed because of hypercholesterolemia and elevated transaminases and revealed hepatosplenomegaly, which in conjunction with other signs and symptoms, suggested the diagnosis of NPC. The diagnosis was confirmed by demonstration of lysosomal storage of unesterified cholesterol (filipin staining) and of a reduced rate of LDL-induced cholesterol esterification. Implication of the NPC1 gene was assessed by genetic complementation analysis., Discussion: The phenotypic presentation of NPC is remarkably variable. The rarer adult-onset form has a slowly progressive course. Psychotic manifestations are often prominent and may precede neurologic symptoms. Exposure to neuroleptics delays the diagnosis of NPC., Conclusion: Psychotic manifestations associated with cerebellar syndrome, vertical supranuclear gaze palsy, and splenomegaly are very suggestive of NPC disease which can be reliably diagnosed on cultured skin fibroblasts by filipin staining.

Diseases due to mutations in the lamin A/C gene (LMNA) are highly heterogeneous, including neuromuscular and cardiac dystrophies, lipodystrophies, and premature ageing syndromes. In this study we characterized the neuromuscular and cardiac phenotypes of patients bearing the heterozygous LMNA R482W mutation, which is the most frequent genotype associated with the familial partial lipodystrophy of the Dunnigan type (FPLD). Fourteen patients from two unrelated families, including 10 affected subjects, were studied. The two probands had been referred for lipoatrophy and/or diabetes. Lipodystrophy, exclusively observed in LMNA-mutated patients, was of variable severity and limited to postpubertal subjects. Lipodystrophy and metabolic disturbances were more severe in women, even if an enlarged neck was a constant finding. The severity of hypertriglyceridemia and hirsutism in females was related to that of insulin resistance. Clinical muscular alterations were only present in LMNA-mutated patients. Clinical and histological examination showed an invalidating, progressive limb-girdle muscular dystrophy in a 42-yr-old woman that had been present since childhood, associated with a typical postpubertal FPLD phenotype. Six of eight adults presented the association of calf hypertrophy, perihumeral muscular atrophy, and a rolling gait due to proximal lower limb weakness. Muscular histology was compatible with muscular dystrophy in one of them and/or showed a nonspecific excess of lipid droplets (in three cases). Immunostaining of lamin A/C was normal in the six muscular biopsies. Surprisingly, calpain 3 expression was undetectable in the patient with the severe limb-girdle muscular dystrophy, although the gene did not reveal any molecular alterations. At the cardiac level, cardiac septal hypertrophy and atherosclerosis were frequent in FPLD patients. In addition, a 24-yr-old FPLD patient had a symptomatic second degree atrioventricular block. In conclusion, we showed that most lipodystrophic patients affected by the FPLD-linked LMNA R482W mutation show muscular and cardiac abnormalities. The occurrence and severity of the myopathic and lipoatrophic phenotypes varied and were not related. The muscular phenotype was evocative of limb girdle muscular dystrophy. Cardiac hypertrophy and advanced atherosclerosis were frequent. FPLD patients should receive careful neuromuscular and cardiac examination whatever the underlying LMNA mutation.

Design: To determine the impact of a neuropediatrician view on diagnosis and management of learning disabilities., Method: Retrospective review of the medical records of the last 100 children attending for learning disabilities from 1st June 2000 through 31st May 2001. Assessment concerned school curriculum, type of management before consultation, diagnosis procedure and type of management following consultation. Differential diagnosis was made in 100% of cases following evaluation., Results: The three main diagnoses were attentionnal deficit disorder with hyperactivity (39%), mental retardation (17%) and dyslexia (7%). Mental retardation and cerebral palsy diagnoses had not been made before consultation. Conversely, 70% of the diagnoses of dyslexia made before consultation were incorrect. Medical treatment was proposed in 38% of cases and modification in the management in 59% of cases., Conclusion: This study highlights the interest of a rigorous diagnosis procedure for learning disabilities, based on a neuropediatrics examination, a cognitive evaluation and phonological and lexical evaluation. It only may lead to an appropriate management.

A maternally inherited and practically homoplasmic mitochondrial (mtDNA) mutation, 8527A>G, changing the initiation codon AUG into GUG, normally coding for a valine, was observed in the ATP6 gene encoding the ATPase subunit a. No alternate Met codon could replace the normal translational initiator. The patient harboring this mutation exhibited clinical symptoms suggesting a mitochondrial disease but his mother who carried the same mtDNA mutation was healthy. The mutation was absent from 100 controls and occurred once amongst 44 patients suspected of Leber Hereditary Optic Neuropathy (LHON) but devoid of typical LHON mutations. In patient fibroblasts, no effect of 8527A>G mutation could be demonstrated on the biosynthesis of mtDNA-encoded proteins, on size and the content of ATPase subunit a, on ATP hydrolysis and on mitochondrial membrane potential. In addition, ATP synthesis was barely decreased. Therefore, GUG is a functional initiation codon for the human ATP6 gene.

In the course of a mutation search performed by muscle dystrophin transcript analysis in 72 Duchenne and Becker Muscular Dystrophies (DMD/BMD) patients without gross gene defect, we encountered four unrelated cases with additional out-of-frame sequences precisely intercalated between two intact exons of the mature muscle dystrophin mRNA. An in silico search of the whole dystrophin genomic sequence revealed that these inserts correspond to cryptic exons flanked by one strong and one weak consensus splice site and located in the mid-part of large introns (introns 60, 9, 1M, and 62, respectively). In each case we identified an intronic point mutation activating the cryptic donor or acceptor splice site. The patients exhibited a BMD/intermediate phenotype consistent with the presence of reduced amounts of normally spliced transcript and normal dystrophin. The frequency of this new type of mutation is not negligible (6% of our series of 65 patients with 'small' mutations). It would be missed if the exploration of the DMD gene is exclusively performed on exons and flanking sequences of genomic DNA.

Background: Percutaneous endoscopic gastrostomy (PEG) is a simple and reliable method, but there are few data about its use in pediatric forms of neuromuscular diseases (NMD). The aim of this study was to evaluate the nutritional effects and tolerance of gastrostomy feeding in NMD patients., Methods: Twelve patients with NMD, ranging in age from 1 month to 25.5 years, underwent a gastrostomy placement (PEG, n = 11; surgical gastrostomy, n = 1) between January 1990 and December 2000. Diseases were muscular dystrophies (n = 5), infantile spinal muscular atrophies (n = 3), congenital myopathies (n = 3), and polyradiculoneuritis (n = 1). Height-for-age (Z(H/A)), weight-for-age (Z(W/A)), and weight-for-height (Z(W/H)) z scores were assessed at birth, at the time of gastrostomy placement, after a 6-month and 1-year follow-up, and at the end of follow-up. Complications that occurred during the gastrostomy feeding period were recorded. Comparisons of z scores at the different times were performed with repeated-measures analyses of variance., Results: Z(W/A) (p < .05) and Z(W/H) (p < .001) improved in the whole group after gastrostomy. For the 10 patients for whom follow-up was more than 1 year, Z(W/A) (p < .03) and Z(W/H) (p < .001) increased from the time of gastrostomy to the end of follow-up. Among 5 patients who had a gastroesophageal reflux diagnosed before gastrostomy placement, 3 had at least 1 episode of pneumonia and 2 died of respiratory distress caused by the worsening of NMD. No other major complication was encountered., Conclusions: Gastrostomy feeding is well tolerated and results in an improvement of nutritional indices in NMD patients. Special care should be taken in patients with preexisting gastroesophageal reflux.

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of the elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and life-threatening cardiomyopathy with conduction blocks. We recently identified LMNA encoding two nuclear envelope proteins, lamins A and C, to be implicated in the autosomal dominant form of EDMD. Here, we report on the variability of the phenotype and spectrum of LMNA mutations in 53 autosomal dominant EDMD patients (36 members of 6 families and 17 sporadic cases). Twelve of the 53 patients showed cardiac involvement exclusively, although the remaining 41 all showed muscle weakness and contractures. We were able to identify a common phenotype among the patients with skeletal muscle involvement, consisting of humeroperoneal wasting and weakness, scapular winging, rigidity of the spine, and elbow and Achilles tendon contractures. The disease course was generally slow, but we observed either a milder phenotype characterized by late onset and a mild degree of weakness and contractures or a more severe phenotype with early presentation and a rapidly progressive course in a few cases. Mutation analysis identified 18 mutations in LMNA (i.e., 1 nonsense mutation, 2 deletions of a codon, and 15 missense mutations). All the mutations were distributed between exons 1 and 9 in the region of LMNA that is common to lamins A and C. LMNA mutations arose de novo in 76% of the cases; 2 of these de novo mutations were typical hot spots, and 2 others were identified in 2 unrelated cases. There was no clear correlation between the phenotype and type or localization of the mutations within the gene. Moreover, a marked inter- and intra-familial variability in the clinical expression of LMNA mutations exists, ranging from patients expressing the full clinical picture of EDMD to those characterized only by cardiac involvement, which points toward a significant role of possible modifier genes in the course of this disease. In conclusion, the high proportion of de novo mutations together with the large spectrum of both LMNA mutations and the expression of the disease should now prompt screening for LMNA in familial and sporadic cases of both EDMD and dilated cardiomyopathy associated with conduction system disease.

Three cases of epignathus teratoma associated with other midline anomalies are reported. The first case involved Pierre Robin sequence and a bifid tongue. The second case was characterized by two teratomas, a meningoencephalocele, and a cleft lip and nose. The third case had Pierre Robin sequence associated with duplication of the pituitary gland and hypoplasia of the corpus callosum.

Febrile convulsions are the main etiology of the occasional convulsions. They occur between 6 months and 5 years. They are short, bilateral, clonic or tonico-clonic. Febrile convulsions are classified in 2 groups: benign febrile convulsions and complicated febrile convulsions. When it exists, the genetic predisposition is a significant factor recurrent of febrile convulsions, but their prognosis remains good. Treatment depends on the diagnosis of simple or complicated febrile convulsions. The treatment of febrile convulsions is intra-rectal diazepam (0.5 mg/kg). The risks of recurrence of convulsions are inversely proportional to the intensity and duration of the fever episode before the convulsion.

Background: Semi-lobar holoprosencephalies can be seldom complicated by neurogenic hypernatremia, which must be distinguished from other causes of hypernatremia., Case Report: In two admitted children with semi-lobar holoprosencephaly, 7 months and 4 years old, biological data revealed chronic hypernatremia and hyperosmolarity without clinical signs of dehydration, which were finally attributed to a neurogenic hypernatremia., Conclusion: Neurogenic hypernatremia must be clearly differentiated from other causes of hypernatremia since it never causes specific complications.

Benign acquired and isolated asymmetrical palatal palsy is a rare condition in childhood. We report on three cases. Typical features include: sudden onset, abnormality of the palatal components of speech (rhinolalia), nasal escape of fluids from the ipsilateral nostril. It is supposed to be caused by viral infection, but attempts at viral isolation were unsuccessful. Complete spontaneous recovery is usual, taking a few weeks. Our paper seems to be the first report of magnetic resonance imaging of the brain in this condition. It did not disclose any abnormalities in the 2 cases in which it was performed.

Background: Myoclonic epilepsy of infancy are seldom benign., Case Report: A 25-month old girl developed myoclonic jerks either spontaneously either as reflex responses to auditory and tactile stimuli, such as sudden touching of the face or trunk from the age of 4 months. The jerks disappeared after valproate therapy. Neurological examination was normal with a follow-up of 9 months., Conclusion: This condition resembles that described in 1995 by Ricci et al. In must be differentiated from other myoclonic epilepsies of infancy, reflex epilepsies and hyperekplexia. It could be the earliest from of idiopathic generalized epilepsy.