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Children with cerebrotendinous xanthomatosis: clinical spectrum and response to treatment
Society Proceedings / Clinical Neurology and Neurosurgery 99 (1997) 73 75 test seems an easy and cl:eap method for the first screening in a clinical setting of the visual field defects in CP. Data obtained seem of great importance for the diagnosis and the management of this disorder. 8 Disease of the vanishing white matter M.S. van der Knaap ", P.G. Barth b, F.J.M. Gabrefils~ S. Naidu d, H.W. Moser d, ~Department o/"
CTlild Neurology, Free University Hospital, Amsterdam; bDepartment of Paediatrics, Academic Medical Center, Amsterdam; tinterdisciplinary Child Neurglogy Institute, St. Radboud tlospital, Nijmegen, The Netherla.qds: and 'JDepartment of Neurogenetics. Kenned), Krieger Institute, Baltimore, USA Among the progressive leukoencephalopathies of unknown origin a new identity can be defined based on clinical and magnetic resonance imaging (MRI) findings. We were able to identify 20 patients. The disease has its onset in early childhood and has a chronic-progressive course with episodes of rapid deterioration following infections and minor head injuries. These episodes may lead to unexplained coma or subcoma. MRI shows a diffuse leukoencephalopathy involving the cerebral hemispheres. Part ,gf the abnormal white matter has a signal intensity similar to that of CSF on all pulse sequences. MR spectra of the white matter show an almost complete disappearance of all normal signals and presence of some glucose and lactate compatible with the presence of mainly CSF and little brain tissue. MR spectra of the cortex all show normal signals with relatively (although not completely) normal ratios, and additionally more or less prominent signals representing lactat,,• and glucose. Autopsy in one patient confirmed the presence of extensive cystic degeneration of the cerebral hemispheral white mat':er and preservation of the cerebral cortex. In white matter areas that were not completely cystic, severe loss of myelin with spongy change was noted. The disease has an autosomal recessive mode of inheritance. The basic defect is as yet unknown. A collaborative genetic linkage study has been started. 9 Wilson's disease--C.S.M. Straathof, C.E. Catsman-Berrevoets, De-
partment ~[ Child Neurology, University Hospital Dijkzigt and Sophia Children "s Hospital, Rotterdam, The Netherlands A 14 year old boy, was presented, with progressive dysarthria and swallowing difficulties since he was 6 months. He had been fit and well before; the family histcry was unremarkable and his parents were not related. On neurological examination he had a bulbar dysarthria, a mask-like facial expression, positive glabella and snout reflexes and cogwheel rigidity in the shoulders. MRI of the brain showed diffuse atrophy and on the T2-weighted imaging symmetrical patchy hyperintense lesions in the putamen, globus pallidus complex a~,; well as in the external capsule, caudate nuclei and thalami and in the medial cerebellar peduncle on both sides. Based on a decreased l,,~vels of plasma ceruloplasmin, increased urinary copper excretion and presence of a Kayser-Fleischer ring in the cornea on slit-lamp examination, the diagnosis of Wilson's disease was made. 10 Children with cerebrotendinous xanthomatosis: clinical spectrum and response to treatment--A. Verrips ~, A.F.J. ,,'an Heijst b, W.O. Renier ~, R.A. Wevers a, J.R.M. Cruysberg ¢, J.J.M. Tolboom b, ~De-
partments oJ Neurology, "Pediatrics and ¢Ophthalmology, University Hospital Radboud, Nijm~'gen, The Netherlands We describe the clinical spectrum of Cerebrotcndinous Xanthomatosis (CTX) in childhood and the effect of treatment with chenodeoxycholic acid (CDCA) over a period of 5 years.
75
In five children with biochemically proven CTX (two males and three females), clinical, genetic, neuroradiologic and neurophysiologic studies were done. All children were treated with CDCA (15 mg/kg/ day) in three divided oral doses. The effects o f therapy were evaluated by determination of the serum cholestanol/cholesterol ratio (CCR) and the urinary excretion of bile alcohols. Diarrhoea and premature cataract were the main clinical features. Psychomotor retardation, pyramidal and cerebellar signs were also found. After starting treatment, biochemical abnormalities normalized and diarrhoea disappeared. After 1 year of therapy there was no further delay in motor development, and in three children the intelligence quotient improved. EEG abnormalities disappeared. After 5 years of therapy the children showed a stable clinical condition. We conclude that the clinical, biochemical and neurophysiological parameters in these five children with CTX showed a remarkable improvement after starting treatment with chenodeoxycholic acid. The early diagnosis of CTX and the start of treatment with chenodeoxycholic acid has prevented neurological deterioration for a period of 5 years. 11 Epilepsy and clinical spectrum of t)- and L-2-hydroxyghitaric aciduria Y . Geerts, W.O. Renier, Interdisciplinary Child Neurol-
ogy Institute, St. Radboud Hospital, Nijmegen, Ttre Netherlands One of the causes of infantile spasms can be an inborn error of metabolism. 2-hydroxyglutaric aciduria is a rare neurometabolic disorder that is often characterized by seizures and developmental delay. We recently made a diagnosis of ]>-2-hydroxyglutaric aciduria in an infant. By reviewing the literature on hydroxyglutaric aciduria, we identified six patients with the D-isomer and 24 patients with the L-isomer. Although the clinical information is not always complete, most patients with the D-form have an early onset of symptoms with a severe developmental delay and refractory epilepsy. No correlation has been found between the concentration of 2-hydroxyglutaric acid in body fluids and the severity of the disease. 12 Two sisters with severe childhood autosomal recessive muscular dystrophy (SCARMD) with a v-sarcoglycanopathy mapped on chromosome 13q12--D. Broere '~, W.H.J.P. Linssen '~, H.B. Ginjaar b, L.M.E. Smit¢, aDepartment of Neurology, St. Lucas-Andreas Hospi-
tal, Amsterdam; bDepartment of Human Genetics, State University Leiden, Leiden; ~Department oJ ChiM Neurology, Free University Hospital, Amsterdam, The Netherlands" An 8 year old girl was admitted because of walking difficulties. Her complaints had been progressive over the last 3 years. During the last year she experienced difficulty in climbing stairs and rising from a chair. Her sister, who was I year younger, had developed similar complaints. The family history was unremarkable: both parents originated from Morocco and they were nonconsanguineous. Neurological examination showed symmetrical shoulder and pelvic girdle weakness in both children. Walking was only possible with knee hyperextension and increased lumbar lordosis. They had firm calves. Gowers sign was present. Facial weakness was absent. Biochemical examination showed a markedly elevated serum creatine kinase (3800 and 10280 U/l, respectively). CT of the muscles revealed atrophy and density changes most prominent in the adductor Iongus and hamstrings. Muscle biopsy showed dystrophic features. Immunostaining of the dystrophin-associated proteins (DAPs) showed deficiency of y-sarcoglycan. DNA analysis suggested a chromosome abnormality mapped on 13q 12.
CTlild Neurology, Free University Hospital, Amsterdam; bDepartment of Paediatrics, Academic Medical Center, Amsterdam; tinterdisciplinary Child Neurglogy Institute, St. Radboud tlospital, Nijmegen, The Netherla.qds: and 'JDepartment of Neurogenetics. Kenned), Krieger Institute, Baltimore, USA Among the progressive leukoencephalopathies of unknown origin a new identity can be defined based on clinical and magnetic resonance imaging (MRI) findings. We were able to identify 20 patients. The disease has its onset in early childhood and has a chronic-progressive course with episodes of rapid deterioration following infections and minor head injuries. These episodes may lead to unexplained coma or subcoma. MRI shows a diffuse leukoencephalopathy involving the cerebral hemispheres. Part ,gf the abnormal white matter has a signal intensity similar to that of CSF on all pulse sequences. MR spectra of the white matter show an almost complete disappearance of all normal signals and presence of some glucose and lactate compatible with the presence of mainly CSF and little brain tissue. MR spectra of the cortex all show normal signals with relatively (although not completely) normal ratios, and additionally more or less prominent signals representing lactat,,• and glucose. Autopsy in one patient confirmed the presence of extensive cystic degeneration of the cerebral hemispheral white mat':er and preservation of the cerebral cortex. In white matter areas that were not completely cystic, severe loss of myelin with spongy change was noted. The disease has an autosomal recessive mode of inheritance. The basic defect is as yet unknown. A collaborative genetic linkage study has been started. 9 Wilson's disease--C.S.M. Straathof, C.E. Catsman-Berrevoets, De-
partment ~[ Child Neurology, University Hospital Dijkzigt and Sophia Children "s Hospital, Rotterdam, The Netherlands A 14 year old boy, was presented, with progressive dysarthria and swallowing difficulties since he was 6 months. He had been fit and well before; the family histcry was unremarkable and his parents were not related. On neurological examination he had a bulbar dysarthria, a mask-like facial expression, positive glabella and snout reflexes and cogwheel rigidity in the shoulders. MRI of the brain showed diffuse atrophy and on the T2-weighted imaging symmetrical patchy hyperintense lesions in the putamen, globus pallidus complex a~,; well as in the external capsule, caudate nuclei and thalami and in the medial cerebellar peduncle on both sides. Based on a decreased l,,~vels of plasma ceruloplasmin, increased urinary copper excretion and presence of a Kayser-Fleischer ring in the cornea on slit-lamp examination, the diagnosis of Wilson's disease was made. 10 Children with cerebrotendinous xanthomatosis: clinical spectrum and response to treatment--A. Verrips ~, A.F.J. ,,'an Heijst b, W.O. Renier ~, R.A. Wevers a, J.R.M. Cruysberg ¢, J.J.M. Tolboom b, ~De-
partments oJ Neurology, "Pediatrics and ¢Ophthalmology, University Hospital Radboud, Nijm~'gen, The Netherlands We describe the clinical spectrum of Cerebrotcndinous Xanthomatosis (CTX) in childhood and the effect of treatment with chenodeoxycholic acid (CDCA) over a period of 5 years.
75
In five children with biochemically proven CTX (two males and three females), clinical, genetic, neuroradiologic and neurophysiologic studies were done. All children were treated with CDCA (15 mg/kg/ day) in three divided oral doses. The effects o f therapy were evaluated by determination of the serum cholestanol/cholesterol ratio (CCR) and the urinary excretion of bile alcohols. Diarrhoea and premature cataract were the main clinical features. Psychomotor retardation, pyramidal and cerebellar signs were also found. After starting treatment, biochemical abnormalities normalized and diarrhoea disappeared. After 1 year of therapy there was no further delay in motor development, and in three children the intelligence quotient improved. EEG abnormalities disappeared. After 5 years of therapy the children showed a stable clinical condition. We conclude that the clinical, biochemical and neurophysiological parameters in these five children with CTX showed a remarkable improvement after starting treatment with chenodeoxycholic acid. The early diagnosis of CTX and the start of treatment with chenodeoxycholic acid has prevented neurological deterioration for a period of 5 years. 11 Epilepsy and clinical spectrum of t)- and L-2-hydroxyghitaric aciduria Y . Geerts, W.O. Renier, Interdisciplinary Child Neurol-
ogy Institute, St. Radboud Hospital, Nijmegen, Ttre Netherlands One of the causes of infantile spasms can be an inborn error of metabolism. 2-hydroxyglutaric aciduria is a rare neurometabolic disorder that is often characterized by seizures and developmental delay. We recently made a diagnosis of ]>-2-hydroxyglutaric aciduria in an infant. By reviewing the literature on hydroxyglutaric aciduria, we identified six patients with the D-isomer and 24 patients with the L-isomer. Although the clinical information is not always complete, most patients with the D-form have an early onset of symptoms with a severe developmental delay and refractory epilepsy. No correlation has been found between the concentration of 2-hydroxyglutaric acid in body fluids and the severity of the disease. 12 Two sisters with severe childhood autosomal recessive muscular dystrophy (SCARMD) with a v-sarcoglycanopathy mapped on chromosome 13q12--D. Broere '~, W.H.J.P. Linssen '~, H.B. Ginjaar b, L.M.E. Smit¢, aDepartment of Neurology, St. Lucas-Andreas Hospi-
tal, Amsterdam; bDepartment of Human Genetics, State University Leiden, Leiden; ~Department oJ ChiM Neurology, Free University Hospital, Amsterdam, The Netherlands" An 8 year old girl was admitted because of walking difficulties. Her complaints had been progressive over the last 3 years. During the last year she experienced difficulty in climbing stairs and rising from a chair. Her sister, who was I year younger, had developed similar complaints. The family history was unremarkable: both parents originated from Morocco and they were nonconsanguineous. Neurological examination showed symmetrical shoulder and pelvic girdle weakness in both children. Walking was only possible with knee hyperextension and increased lumbar lordosis. They had firm calves. Gowers sign was present. Facial weakness was absent. Biochemical examination showed a markedly elevated serum creatine kinase (3800 and 10280 U/l, respectively). CT of the muscles revealed atrophy and density changes most prominent in the adductor Iongus and hamstrings. Muscle biopsy showed dystrophic features. Immunostaining of the dystrophin-associated proteins (DAPs) showed deficiency of y-sarcoglycan. DNA analysis suggested a chromosome abnormality mapped on 13q 12.