Tyrosine hydroxylase deficiency; clinical presentation, biochemistry and treatment in four dutch cases

Clinical Neurology and Neurosurgery ELSEVIER

Clinical Neurology and Neurosurgery 99 (19971 73 75

Society Proceedings

Netherlands Society of Child Neurology Sneek, Netherlands, 31 May 1996 Secretariat: Netherlands Society of Child Neurology c/o L.M.E. Smit, Department of Child Neurology, Free University Hospital, P.O. Box 7057, 1007 MB Amsterdam, Netherlands Received 29 August 1996: accepted 5 September 1996

1 An infant with epilepsy: adenylosuccinase deficiency- P.D. Maaswinkel-Mooij~, L.A.E.M. Laan b, O.F. Brouwer h, B.J.H.M. Poorthuis", ~Departments ,¢ Pediatrics and b:Veurology, Leiden Uni-

versity Hospital, Leiden, The :Vetherlands Adenylosuccinase deficiency is an inborn error of purine metabolism. Patients are detected by the finding of the metabolites suceinylaminoimidazole carboxamide riboside and succinyladenosine in urine and cerebrospinal tluid. For screening, a spot-test is available, indicating the presence of succinylpurines. Sixteen patients with adenylosuceinase deficiency have been described. All presented with ,;evere psychomotor retardation; epilepsy developed in early childhood in most patients. Autism and poor visual contact were often reported. We describe a girl who was diagnosed at the age of 9 weeks when she was admitted because of generalized tonic-clonic seizures. At the age of 13 months infantih; spasms were noticed with the EEG showing typical hypsarrythmia. At the age of 21 months shc had a convulsive status epilepticus, followed by recurrent seizures. Initially, psychomotor development was slow, but in the second year of life severe mental retardation became apparent. Magnetic resonance imaging of the brain revealed generalised cortical and cerebellar atrophy with patches of dysmyelination in the sub,cortex and in the deep white matter. We conclude that screening for adenylosuccinase deficiency should be performed in young children with psychomotor retardation or .seizures of unknown etiology'.

2 Visual acuity in children with hydrocephalus-. K.T.M. Oud. S.J. Steggerda, V.M.H. Nanninga-Van den Neste, R.H.J.M. Gooskens, O. van Nieuwenhuizen, Department of ChiM Neuroh~gy, Wilhelmina

Children ~ Hospital Utreo~t Several studies have described disturbances of visual function in children with hydrocephalu.,. Low vision in hydrocephalic children may bc associated with ophthalmological defects, but can also be caused by a defective function of the retrochiasmatic part of the visual system (cerebral visual impairment; CVI). The aim of the present study was (1) to assess the prevalence of low visual acuity in children with controlled hydrocephalus and to determine the etiology of the visual loss (ophthalmological disorder or a cerebral lesion); (2) to assess the correlation between the degree of ventricular dilatation and visual impairment in children with 0303-8467:97;$17.00 ~_3 1997 Elsevier Science B.V. All rights reserved. PII S 0 3 0 3 - 8 4 6 7 ( 9 6 ) 0 0 5 8 7 - 2

hydrocephalus and to determine the relationship between the occurrence and localization of the parenchymal damage in the visual areas and the presence of a visual handicap; and (3) to assess the correlation between the number of shunt dysfunctions in hydrocephalic children and the presence of a visual handicap. The study was carried out in a group of 73 children with controlled hydrocephalus, seen in the outpatient departments of Child Neurology and Neurosurgery, Wilhelmina Children's Hospital in Utrecht during a period between December 1988 and June 1991. Visual acuity was assessed using Teller Acuity Cards. I lalf of the children with controlled hydrocephalus had a vision below the 10th centile of normal children; 94% of these children were diagnosed as suffering from CV1. A correlation was found between (1) parenchymal damage and low visual acuity, and (2) the number of shuntdysfunctions and low visual acuity. No correlation was found between ventricular dilatation and low vision. These findings indicate the importance of regular visual assessment in children suffering from hydrocephalus.

Tyrosine hydroxylase deficiency; clinical presentation, biochemistry and treatment in four dutch cases--J.F, de Rijk-Van AndeP, J.F. Weversb, R.A. Bartholome", K. Blau 'j, F.J.M. Gabre~ls ~, ~Depart-

ment q/Neurolog)', Ignatius Hospital Breda, The Netherlands: bLaboratory q[" Pediatrics and Neurology, University of Nijmegen, The Netherlands; CDepartment of Clinical Genetics, University Hospital Bochern, Germany: aDepartment ¢~f £7inical Chemistry, Children"s Hospital, University of Ziirich, Switzerland, ~Department ~ Child Neurology, Unwersity of N!]megen, The Netherlands Four unrelated children, two boys and two girls, age ranging from 11 to 38 months, presented with unexplained .severe psychomotor retardation and an apparent hypertonic tetraparesis combined with hypokinesia and axial hypotonia in the first months of life. They were born following a normal pregnancy and delivery. In one child the parents were consanguineous. No diurnal fluctuation in s~cmptoms was observed. The EEGs showed a monomorphous background pattern. Neuro-imaging of the brain (CT and MRI) was without abnormalities. In CSF the concentration of homovanillic acid (HVA) was low (ranging from 31 to 117 nmol/l, ref. 400-700 nmol/I) with normal 5-HIAA, neopterin, biopterin, phenylalanin and tyrosin. Also in CSF 3-methodoxy 4-hydroxy phenyl ethylene glycol (MHPG), was below the reference range in all children. Dihydropterine reductase activity in blood was normal.

Socicty ProceedoN.~ ('lhm'al .VeuroloKv and Neuro.vurgery 99 (1997) 73 75

74

The observed low IIVA and M t l P G in CSF in combination with normal 5-tlIAA in CSF led to the working hypothesis of tyrosine hydroxylase (TH) deficiency. TH, the initial and rate limiting enzyme in dopamine synthesis, is expressed in h u m a n brain (substantia nigra and locus ceruleous) and adrenal medulla. More direct proof" that TII deficiency is present can be obtained by L-DOPA supplementation. Following treatment with I - D O P A and the decarboxylase inhibitor carbidopa, 3 mg:kg and 0.75 mg.kg divided in three daily doses, respectively, all children showed a rapid spectacular clinical improvement which supports the putative enzyme deficiency. In urine of our tbur patients, both HVA and VMA were low normal and could not be used as diagnostic parameters in individual cases. s y n d r o m e - C . E . Catsman-Berrevocts, Department oJ Child Neurology, Unicersity Hospital Dijkzigt and Sophm Children ~ Hospital, Rotterdam

4 Sunohara

In 1987 Sunohara et al. described three adult men with a syndrome of anosmia, ichthyosis due to steroid sulfatase deficiency, hypogonadotrophic hypogonadism, nystagmus, corneal opacities and mild mental deficiency. Two of the three men also had unilateral kidney agenesis. We present a 2 year old boy with psychomotor retardation and ichthyosis due to steroid sulfatase deticiency. Ophthalmological examination showed retinitis pigmentosa and severe hypermetropia. MRI showed a slight hydrocephalus and agenesis of the olfactory bulbs as well as hypoplasia of the olfactory sulci. In addition a unilateral renal agenesis was demonstrated. Olfactory agenesis is one of the hallmarks of the Kallmann syndrome, together with a hypogonadotrophic hypogonadism due to decreased luteinizing hormone-releasing hormone secretion. This hormonal deficiency could not yet be demonstrated in our patient because of his young age. D N A analysis showed a deletion on the X - c h r o m o s o m e in the region of the Kallmann gene and the Steroid Sulfatase gene. These genes are situated adjacently on Xp22.3 with a distance of 820 kb. Therefore, we conclude that in Sunohara syndrome the signs of X-linked ichthyosis and Kallmann syndrome coexist and that the syndrome is caused by an extended deletion in the Xp22.3 region. Until now this extended deletion has been de~ribed in 14 patients. 5 Perinatal motor behaviour and neurological outcome in spina bifida aperta- D.A. SivaP, J.H. Begeer", I-I.F.R. Prechtl t', "Department o/

Neurology, Unirersity tlospital Gron#lgen. The Netherlands; t'Department of Physiology. University o/ Graz, Austria Ultrasound observations in fetuses with spina bitida aperta have shown the presence of fetal leg movements despite severe spinal dysraphism. The objective of the present study was to gain insight in the nature of these pre-natal leg movements. Thirteen cases were included in the stud)' with eithcr a thoracal (n = 8) or lumbal defect (n = 5) of the vertebral spine. In these cases, pre- and post-natal motor behaviour was recorded longitudinally by means of ultrasound registrations and videorecordings, respectively, and scored for the presence of leg movements and movement quality by means of gestalt perception. These data were related to (1) the spinal localisation of thc meningo-myeloccle: (2) neonatal motor behaviour: and (3) the results of neurological investigation and motor outcome up to 18 months. Unexpectedly, in all fetuses spontaneous lcg movements related to spinal function of segments below the meningomyelocele were observed. In contrast to these discrepant prenatal leg movements, post-natal leg movements were qualitatively abnormal and they showed a strong tendency to disappear within hours. In contrast to motor function, early post-natal sensory function was correlated to the spinal Iocalisation of the meningomyelocelc (r = 0.76: P = 0.005)

and to final motor outcome. These data on fetuses:infants with spina bifida strongly indicate a discrepancy between I I) the occurrence of prenatal leg movements and the spinal Iocalisation of the meningo-myelocele, and (2) the appearance of pre- and post-natal leg movements. 6 Hyperekplexia; a clinical, genetical, and neurophysiological study M.A.J. Tijssen:'. J.G. van Dijk t', ;'Departments of Neurology and

"(Zinical :\"europhysioh~gy, Leiden University Hoa7~ital. Lei&'n, The NetkerlamZs Hyperekplexia, or Startle Disease, is an autosomal dominant disorder, characterized by excessive startle reflexes to unexpected, especially auditory, stimuli. Two forms of hyperekplexia were recognized in a large Dutch pedigree. The 'major" form consists of excessive startle responses with stiffness related to the startle response and a continuous stiffness in the first years of life. The 'minor" form only shows excessive startle responses without signs of stiffness. Genetic studies identified a point mutation in the gene encoding the :xl subunit of the glycine receptor on chromosome 5q33. This point mutation was also identified in the Dutch pedigree in patients with the 'major' form, but not in those with the "minor' f o r m Neurophysiological studies showed that the startle responses in the "major" form are enlarged and habituation is more pronounced than in normal subjects. In patients with the 'minor' form, startle responses were enlarged, delayed and showed no habituation to repetitive stimuli. Clinical, genetical and neurophysiological studies in the Dutch pedigree consistently show differences between the 'major' and "nilnor" form of hyperekplexia. The origin of the "minor" form is still unknovcn. 7 A new and simple method for testing the monocular and binocular visual field in cerebral palsy (CP): our experience on 31 children in a clinical setting--.G. Porro'L J. | l o f f m a n n '~, D. Wittebol-Post", A.J.F. Schenk Rootlieb b, O. van Nieuwenhuizen", W.F. Treffers",

"Departments o[ Ophthalmology and hChild Neurology, Universio' llospital and Wilhelmina Children ~ Hospital, Utrecht. The Netherland~ A basic aspect of the ophthalmological investigation in subjects with cerebral palsy (CP) is the visual field extension. We have developed a new and easy test, the BEFIE-test (behavioural visual field screening in a clinical setting), useful to assess the behavioural visual field of children with CP in a normal clinical routine. A quantitative extension of the visual field along four diagonal meridians was measured using a 6 ° white ball on a curved graded stick by an examiner placed behind the subject, who was seated in his wheelchair or on his parent's knees. A blind observer had to monitor the subject's tixation and any eye or head movements, in order to make a forced choice on the stimulus position. Thirty-two children with CP aged 1-13 years (mean 5 years and 11 months) were examined. Normal values were obtained in a control group of 60 healthy children and 12 adults. The extension of the normal peripheral visual field increased progressively along each meridian tested approximately until 5 years of age. To establish the reference values, 2 S.D. for adults and 4 S.D. for children were subtracted from the mean values for each age grot.p. Twenty one neurologically impaired children (68'7,,) were able to perform the test, 19 (90%) monocularly and two (10%) binocularly. Ten (48"/,,) of the children tested performed below the reference values along one or more meridians: the subsequent visual field defects were clearly related to the brain damage shown by computer tomography (CT) or magnetic resonance imaging (MRI). A m o n g 11 children with CP with normal visual field, only one (10%) had a normal CT; on the opposite, a child with normal neuroimaging showed a bilateral incongruous hemianopia. In spite of its limitations (variability in the speed of the peripheral target or of the contrast between the target and the background), this