Verbal dyspraxia and galactosemia

Classical galactosemia is an autosomal recessive disorder resulting from deficient galactose-1-phosphateuridyl transferase (GALT) activity. Verbal dyspraxia is an unusual outcome in galactosemia. Here we validated a simplified breath test of total body galactose oxidation against genotype and evaluated five potential biochemical risk indicators for verbal dyspraxia in galactosemia: cumulative percentage dose (CUMPCD) of (13)CO(2) in breath, mean erythrocyte galactose-1-phosphate, highest erythrocyte galactose-1-phosphate, mean urinary galactitol, and erythrocyte GALT activity. Thirteen controls and 42 patients with galactosemia took a (13)C-galactose bolus, and the (CUMPCD) of (13)CO(2) in expired air was determined. Patients with <5% CUMPCD had mutant alleles that severely impaired human GALT enzyme catalysis. Patients with > or =5% CUMPCD had milder mutant human GALT alleles. Twenty-four patients consented to formal speech evaluation; 15 (63%) had verbal dyspraxia. Dyspraxic patients had significantly lower CUMPCD values (2.84 +/- 5.76% versus 11.51 +/- 7.67%; p < 0.008) and significantly higher mean erythrocyte galactose-1-phosphate (3.38 +/- 0.922 mg/dL versus 1.92 +/- 1.28 mg/dL; p = 0.019) and mean urinary galactitol concentrations (192.4 +/- 75.8 mmol/mol creatinine versus 122.0 +/- 56.4; p = 0.048) than patients with normal speech. CUMPCD values <5%, mean erythrocyte galactose-1-phosphate levels >2.7 mg/dL, and mean urinary galactitol levels >135 mmol/mol creatinine were associated with dyspraxic outcome with odds ratios of 21, 13, and 5, respectively. We conclude that total body oxidation of galactose to CO(2) in expired air reflects genotype and that this breath test is a sensitive predictor of verbal dyspraxia in patients with galactosemia.     

La psychopathologie de l’enfant dyspraxique

The term “dyspraxia” was coined by Julian de Ajuriaguerra and Mira Stambak in 1964. This clinical term was treated very differently according to which explanatory model was adopted. Nowadays, it is used to refer to developmental coordination disorder in view of its neuro-developmental origin. In any case, the actual clinical situations vary and are often complex. In our opinion, it is first necessary to examine the differential diagnosis: apraxia in children caused by lesions, dysgraphia, simply delayed motor development, non-verbal learning disability syndrome, hemispheric specialisation deficits, pervasive developmental disorders (autisms, Asperger syndrome, atypical autism and other pervasive developmental disorders), mixed specific developmental disorders, multiple developmental disorder, and children with high potential. Next we focus on co-morbidity. Firstly, we look at psychopathological disorders associated with dyspraxia: autism and pervasive developmental disorders, dyscalculia/math disability, dyslexia/reading difficulties, dysphasia accompanied by verbal dyspraxia, intelligence deficiency, anxiety disorders, and attention-deficit hyperactivity disorder (ADHD). Secondly, we examine psychopathological disorders associated with dyspraxia. Children with developmental coordination disorder are less inclined to participate in collective games. As a result, there is a greater risk of them becoming lonely and isolated. They have higher child behaviour checklist (CBCL) scores in the somatic problems scale as well as for anxiety, depression and social withdrawal. They have low self-perception in sports as well as at school, which is related to their physical appearance and their self-esteem, attention deficit and externalized behaviour. These children are often at risk of academic failure and they suffer from oppositional defiant disorder and functional disorders. And finally, we believe that it is important to touch on the impact of these disorders on the family.     

Dyspraxia or developmental coordination disorder? Unravelling the enigma.

Dyspraxia is an enigma to many people, both professional and lay alike--what is it, how does it relate to developmental coordination disorder and associated conditions, how common is it, how is it recognised and diagnosed and how should it be managed? This article attempts to unravel this enigma by: dealing with the terminology of coordination difficulties from the "clumsy child syndrome" through "dyspraxia" to "developmental coordination disorder (DCD)"; briefly examining the debate as to whether dyspraxia or DCD should be regarded as a medical or social disorder; discussing the differential diagnosis of dyspraxia or DCD; considering the assessment of children with dyspraxia or DCD; reviewing the range of current treatment approaches in the UK.     

Identification de critères diagnostiques des sous-types de troubles de l’acquisition de la coordination (TAC) ou dyspraxie développementale

The aim of the study was to identify clear clinical signs and symptoms, which are specific of developmental coordination disorder (DCD) or developmental dyspraxia subtypes.     

Non-verbal learning disabilities: developmental dyspraxia]

Dyspraxia is a non verbal neuropsychological dysfunction still unrecognized but which can generate scholar learning and behavioural disabilities. We propose, at first time, to do a state of art with the various terminologies and typologies which lead to put together clumsiness, motor coordination disorder and the different types of dyspraxia. Then, we will bring an integrative model and clinical data in children with developmental dyspraxia, allowing a better pointing, to make a diagnostic and then we suggest some advices for remediations.     

Practitioner Review: Developmental Language Disorders: A Clinical Update

Non-specialists can identify three types of developmental language disorder. (1) mixed receptive/expressive disorders, which impair phonology, syntax, and semantics. Children who understand nothing are nonverbal, in others speech is sparse, nonfluent, poorly intelligible, and agrammatic; (2) expressive disorders with adequate comprehension affect phonologic production-predominantly. Children with verbal dyspraxia, the most severe variant, may also be nonverbal but comprehend well; (3) higher order processing disorders affect semantics, pragmatics, and discourse. Semantics and pragmatics are invariably affected in preschool autistic children in whom isolated expressive deficits do not occur. Etiology of developmental language disorders is predominantly genetic. Structural brain lesions detectable by neuroimaging are exceptional. Severe receptive deficits require a sleep EEG to detect subclinical epilepsy. Early educational intervention is both critical and efficacious.     

Defekt der langkettigen 3-Hydroxy-Acyl-CoA-Dehydrogenase—LCHAD-Defekt

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare inborn disorder of mitochondrial fatty acid β-oxidation. Clinical manifestations include acute symptoms such as hypoketotic hypoglycemia with hepatopathy and encephalopathy and chronic symptoms such as myopathy, cardiomyopathy, neuropathy, and retinopathy. More than 80% of patients with acute manifestations of LCHAD deficiency will die during the first 2 years of life. Fatty acid oxidation defects can now be diagnosed during the initial days of life in the presymptomatic state by newborn screening with tandem mass spectrometry. Screening of 630,000 newborns detected 9 patients with LCHAD defect (a high incidence of 1:30,000 in the north-western part of Germany). We report on the clinical course of two patients with LCHAD defect who were diagnosed by newborn screening during their first 2 years of life. The development of characteristic symptoms in both patients could not be prevented. However, with early and specific therapy both patients showed normal development at the age of 24 months. The hope is that early identification of such patients through newborn screening may improve the prognosis of patients with this disorder.     

Screening newborns for galactosemia using total body galactose oxidation to CO2 in expired air

Classic galactosemia is caused by impaired galactose-1-phosphate uridyltransferase (GALT EC 2.7.712). If discovered and treated within the first days of life, the acute problems of hepatocellular damage, sepsis, and death are prevented. However, chronic problems such as ataxia, tremor, dyspraxic speech, and ovarian failure may occur. To determine whether screening newborns before discharge from the nursery for GALT deficiency is feasible and whether acute and chronic signs could be prevented by earlier intervention, we developed a simplified "breath test." We quantitated total body oxidation of C-D-galactose to CO2 in expired air by normal newborns between 2 h and 2 mo of age and compared their results to older children with GALT deficiency. We found no differences in total body galactose oxidation (TBGO) among normal newborns up to 48 h of age, but a 2-fold rise in TBGO developed during their first 2 wk of life. Older children with galactosemia had significantly less oxidative capacity than normal newborns. We conclude that newborn breath testing for total body galactose oxidation is feasible before discharge from nursery. It has potential utility for both preventing acute neonatal toxicity and determining the mechanisms producing long-term complications such as ovarian failure, dyspraxia, ataxia, and tremors.     

Developmental dysphasia: clinical importance and underlying neurological causes.

This survey deals with two aspects of developmental dysphasia which are relevant to child psychiatry; the early diagnosis and treatment of children with developmental dysphasia, which may prevent the progression of learning and behaviour disorders, and the underlying biological causes of this neuro-developmental disorder. The pathophysiology of developmental dysphasia is complex and age-related. In the pre-verbal and early verbal stage, the severity of the clinical picture is primarily determined by concomitant motor pathology (motor dysfunction, dysarthria, general and oral dyspraxia) and by receptive pathology (hearing and auditory perception). In the verbal period, linguistic problems start to play a role, and often combine with oral motor symptoms to present a mixed picture. The various language syndromes do not become clear until some time later. After the kindergarten period, the oral motor and perceptual problems decrease and the language disorders continue to play a role and influence the child's conversation, internal speech and learning a school. In a relatively small number of children without oral motor, perceptual or memory problems, there can be a basic syndrome of "pure dysphasia" without any other neurological signs. These children are very likely to have a genetically determined developmental disorder on a limited neuronal level (no cerebral damage of any kind!) such as an abnormal asymmetry of the hemispheres. In somewhat more than half the patients, this basic syndrome is accompanied by other neurological signs, most of which are indicative of functional disorders of the left hemisphere. There can also be symptoms of the right hemisphere, of the corpus callosum and of the afferent pathway systems for auditory perception. The nature and causes of these anomalies can be multifarious, so that it is unfeasible to speak of THE substrate or THE pathogenesis. Treatment should not be confined to speech therapy techniques, but should also take into consideration the existence of abnormal motor and affective development and can thus only be optimally given by a highly trained team whose expertise also extends to the schooling aspect.     

A controlled study of psychiatric morbidity among developmentally disabled children in the United Arab Emirates

A cross-sectional study of the prevalence of psychiatric problems among 26 children each with a learning disability (mental retardation) and specific speech disorder was conducted in an Arab population using the Rutter Behavioural Scale, and compared with a community sample of 100 control children matched for age. The prevalence of psychiatric problems, as identified by both the parents and the teachers was 35, 19 and 4 per cent respectively, in the learning disabled, speech impaired and control groups. Children with global disability or mental retardation showed significantly higher rates of psychiatric morbidity than those with specific speech disorder, both of which were significantly higher than that in the control group. Higher rates of psychiatric problems noted in the developmentally disabled children may be the result of specific socio-demographic and cultural factors in addition to neurodevelopmental factors and low IQ.     

Quantitative magnetic resonance imaging of the brain in survivors of very low birth weight.

BACKGROUND: Children who survive very low birth weight (VLBW) without major disability have a high prevalence of learning difficulty, attention deficit, and dyspraxia. AIMS: To determine whether learning difficulty in children with VLBW is associated with structural brain abnormalities. METHODS: A total of 87 children (aged 15-16 years) with a history of VLBW (<1500 g) and eight age matched full term controls have been studied with detailed magnetic resonance brain scans. Volume measurements of the caudate nuclei and hippocampal formations were made. RESULTS: Scans in 42.5% of the children showed evidence of perinatal brain injury. There was no significant difference in IQ, dyspraxia, or attention deficit between children with qualitatively normal and abnormal scans. However, quantitative volumetric analysis showed that children with a low IQ had smaller volume measurements for the right caudate nucleus and left hippocampus, and a smaller hippocampal ratio (left volume:right volume) than those with normal IQ. CONCLUSION: Data suggest that learning disorder, attention deficit, and dyspraxia in children who survive VLBW do not correlate with conventional markers of perinatal brain injury, and may be related to global brain growth and the development of key structures, such as the caudate nuclei and hippocampal formations.     

Quantitative magnetic resonance imaging of the brain in survivors of very low birth weight

Background: Children who survive very low birth weight (VLBW) without major disability have a high prevalence of learning difficulty, attention deficit, and dyspraxia. Aims: To determine whether learning difficulty in children with VLBW is associated with structural brain abnormalities. Methods: A total of 87 children (aged 15–16 years) with a history of VLBW (<1500 g) and eight age matched full term controls have been studied with detailed magnetic resonance brain scans. Volume measurements of the caudate nuclei and hippocampal formations were made. Results: Scans in 42.5% of the children showed evidence of perinatal brain injury. There was no significant difference in IQ, dyspraxia, or attention deficit between children with qualitatively normal and abnormal scans. However, quantitative volumetric analysis showed that children with a low IQ had smaller volume measurements for the right caudate nucleus and left hippocampus, and a smaller hippocampal ratio (left volume:right volume) than those with normal IQ. Conclusion: Data suggest that learning disorder, attention deficit, and dyspraxia in children who survive VLBW do not correlate with conventional markers of perinatal brain injury, and may be related to global brain growth and the development of key structures, such as the caudate nuclei and hippocampal formations.     

Delayed diagnosis of Duchenne muscular dystrophy.

A late diagnosis of Duchenne muscular dystrophy has implications for both child and family. This repeat audit has shown that the diagnosis continues to be delayed. The failure to recognize that non-motor, and specifically speech and language delay are common features of this disease may detract from the motor difficulties in affected children and contribute to the late diagnosis of this disorder. In the absence of a national newborn screening programme for Duchenne muscular dystrophy, all health care professionals should be made more aware of the condition and have a lower threshold for measuring a creatine phosphokinase level.     

Nervous system involvement in HIV1 infections in infants

A prospective survey of 38 HIV1-infected infants has been performed. Thirty-four percent of the patients expressed neurological abnormalities. Three main clinical entities of various intensity have been defined: 8 patients had severe intellectual and motor dysfunctions associated with a bucco-lingual dyspraxia; in 4 patients, the intellectual and motor alterations were less intense but were associated with a severe bucco-lingual dyspraxia; finally one patient had no clinical symptomatology but a chronic lymphocytic meningitis. No opportunistic infection of the CNS was observed. The neurological alterations were correlated in intensity with the immunological dysfunction. CT scans were normal or showed cerebral atrophy in most cases. CSF were normal in 12 cases and a pleiocytosis was observed in one case. However, in 4 of the 6 tested cases, anti-HIV antibodies were detected in CSF.     

Identité et spécificité du « pédantisme » dans le syndrome d’Asperger

The purpose of this work is to better understand pedantic speech in Asperger syndrome as a pervasive developmental disorder. Often mentioned, unlike echolalia in studies on typical autism, this symptom questions the possible specificity of Asperger syndrome. From a review of literature and clinical examples, we propose an interpretation of this speech style as unified and coherent as possible. This clinical feature includes an overly precise vocabulary or overly favourite topic (which can be explained by a more general sameness) in the context of a one-side interaction (which can be explained by a more general impairment of influence). We suggest that the tendency to speak in a pedantic manner may be specific despite a generic disorder shared with typical autism.     

Mass screening for Wilson's disease: Results and recommendations

Wilson's disease is a treatable inherited disorder of copper metabolism. Established treatments include the use of oral chelating agents and the establishment of a minimum copper diet, although prognosis mainly depends on the extent of liver or nervous system damage present before treatment. Once irreversible damage has occurred, the effect of these treatments is diminished and the patient's quality of life compromised. Therefore, the establishment of a mass screening system able to detect Wilson's disease patients presymptomatically has been discussed. Recently, a monoclonal antibody specific to holoceruloplasmin has been developed. This antibody was used in a nationwide screening trial of 126,810 newborn infants, but no Wilson's disease patients were identified. However, three patients out of 24,165 were diagnosed with Wilson's disease using this specific antibody in a screening performed during the period from late infancy to elementary school. The age of 3 years is thought to be the best point for Wilson's disease mass screening. In this paper, a review of mass screening for Wilson's disease in Japan using a specific monoclonal antibody to holoceruloplasmin is presented.     

Decline of acute encephalopathic crises in children with glutaryl-CoA dehydrogenase deficiency identified by newborn screening in Germany

Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare neurometabolic disorder that is considered treatable if patients are identified before the onset of acute encephalopathic crises. To allow early identification of affected individuals, tandem mass spectrometry-based newborn screening for GCDH deficiency has been started in Germany in 1999. We prospectively followed neonatally screened patients (n=38) and compared the neurologic outcome with patients from a historical cohort (n=62). In the majority of neonatally screened children, the onset of encephalopathic crises has been prevented (89%), whereas acute encephalopathic crises or progressive neurologic impairment was common in the historical cohort. Neonatal screening in combination with intensive management is effective--even assuming ascertainment bias in the historical cohort. Similar proportions of commonest mutations and biochemical phenotypes (high and low excretors) were found in neonatally screened and historical patients. However, potential predictor variables for mild clinical phenotypes are not yet known and thus a selection of these patients by newborn screening is not excluded. No patient was known to be missed by newborn screening from 1999 to 2005. In conclusion, this study confirms that newborn screening for GCDH deficiency in combination with intensive management is beneficial.     

Curing dyslexia and attention‐deficit hyperactivity disorder by training motor co‐ordination: Miracle or myth?

Dore Achievement Centres are springing up world-wide with a mission to cure cerebellar developmental delay, thought to be the cause of dyslexia, attention-deficit hyperactivity disorder, dyspraxia and Asperger's syndrome. Remarkable success is claimed for an exercise-based treatment that is designed to accelerate cerebellar development. Unfortunately, the published studies are seriously flawed. On measures where control data are available, there is no credible evidence of significant gains in literacy associated with this intervention. There are no published studies on efficacy with the clinical groups for whom the programme is advocated. It is important that family practitioners and paediatricians are aware that the claims made for this expensive treatment are misleading.