Short communication Moyamoya in Child with Glycogen Storage Disease Type la F- Gouti6res' Disease a M. ~ o u r ~ e o i s ' P. hioche2 I. F. ~ e m e l i e ? odievre2 'Neuropediatric Unit. Hdpital des Enfants Malades. 149, me de Skres, Paris Cedex 15. P. ~ a b r u n e ~ France, 'pediatric Unit. H6pital Antoine B&cl&re,Clarnart Cedex. France, and 3~iochernical Laboratory. Hdpital Robert DebrC, 48 Boulevard Serrurier, Paris Cedex 19, France - Abstract Abbreviations EDAMS: encephaloduroarterio- MRI: magnetic resonance myosynangiosis imaging ICA: intemal carotid artery TTA:transient ischemic attacks MCA: middle cerebral artery GSD: glycogen storage disease Moyarnoya disease is a cerebrovascular disease characterized by repeated cerebral ischemic attacks with progressive occlusion of both internal carotid arteries (ICA) and of their branches and formation of an exuberant collateral network of blood vessels at the base of the brain. It has been first described in Japan as primitive arteriopathy but the disorder may also develop as secondary phenomenon of vascular occlusion in several conditions and it has been reported in children both as a primary phenomenon or associated with underlying disease (1, 8, 9). We report on a child with moyamoya disease and GSD type Ia. Case history and results This Caucasian boy developed normally until the age of 37 months, when, following a mildly febrile pharyngitis he presented one evening a transient weakness of the left side of the body and was found on awakening the following morning with a leftsided paralysis. Since the age of two, his parents recorded bouts of painless hypotonia of the left arm related to "pulled elbow" and retrospectively interpreted as transient ischemic attacks (TIA). Ekamination showed a bright child with a leftsided hemiplegia and pyramidal tract signs predominating in the lower limb. The abdomen was enlarged with a voluminous soft liver reaclung 16 centimeters below the costal margin (which had never been noted before). Blood pressure was 120/80, cardiac and vascular examination were normal. Laboratory investigations showed normal values for serum glucose, electrolytes, urea, bilirubin and cholesterol. WBC count was 7.700/mm3 with 66% neutrophils; platelets: 534.000/mm3; hematocrit: 32.4 %; prothrombin: 93 %; activated parfial prothrombin time: 56 sec (N: ~ 7 0 ) Bleeding . time was 9 min. Abnormal serum values were recorded for triglycerids: 5.9mmoM (N: 0.55 - 1.70),lipoprotein a: 0.81 g/l (N <0.3), SGOT 100 Uyl and SGPT 70 UM (N: 5-20). CSF was normal. Received October 23,1996;revised, accepted February 3, 1997 chance event and an etiological relationship between them must be considered. Key words: Moyamoya disease - Glycogen storage disease type la Cerebral MRI showed on T2-weighted sequences an increased corhcal signal of the right paracentral lobule and a more limited symmetrical lesion on the left side. Partial obstruction of the lumen of the right transverse sinus was seen on MRI angiography. These findings were interpreted as cortical softening following partial thrombosis of the right transverse sinus. Liver biopsy showed macrovesicular s t e a h i s of hepatocytes with normal Kuppfm cells, suggestive of GSD. The diagnosis of GSD type la was c o n f i e d by the enzymatic assay (deficiency of glucose-6phosphatase hepatic activity). Molecular study of the glucose-6phosphatase gene showed that the child was homozygous for the Q 347 X mutation, previously described by Lei et al (7). As the child was able to tolerate a 15-hour fast, he was just given cornstarch (1.5 g/kg) at every meal.The herniplegia progressively resolved and he was left w i b two months with a mild motor deficit limited to the lei? leg. The following months, he episodically presented transient hfficulties to hold an object in his hand, right or left. Nine months after the herniplegia, MRI showed bilateral symmetrical frontoparietal atrophy sequelae of the softening and increased visibility of the vascular network in the deep cerebral white matter and the basal ganglia on both sides, suggestive of moyamoya disease (Fig. 1). This was codinned by angography, showing severe stenosis of both ICA at the level of the siphon with no flow through the right middle cerebral artery (MCA) and minimal flow through the left anterior cerebral artery and distal MCA (Fig. 2). An important anastornotic network through telangiectatic lenticulostriate arteries was developed on both sides. Vertebral injection showed conLribution to the extensive deep collateral vessels through thalamic and posterior choroidal vessels. The angiography did not c o b the thrombosis of the right transverse sinus. Following these findings, the initial frontoparietal softening was retrospectively interpretated as secondary to arterial occlusion. Despite treatment with nirnodipine 15 mg/day, repeated TIA affecting the left arm led to perform an i n h c t revascularization procedure by a right encephaloduroarteriomyosynangiosis(EDAMS). This was followed 36 hours later by complete flaccid left-sidedherniplegia related to postsurgical cerebral edema. Pyracetam (900 mg/day) was added to nimodipine 30 mg/day The left-sided hemiplegia disappeared within two months. Protein S, protein C and antithrombin III plasma concentrations were normal or slightly increased (130 % of controls), anti-cardiolipine IgG antibody was not detected in the serum. At the age of 5 years, contralateral TIA occurred with paralysis of the right arm and aphasia and EDAMS was performed on the left side. Downloaded by: Universite Laval. Copyrighted material. A three-year-old child affected by glycogen storage disease (CSD) type la presented with acute hemiplegia secondary to Moyamoya disease. So far. the association of rnoyamoya with GSD la had only been reported twice. The rarity of both conditions makes their association unlikely to be a Fig. 1 MRI T,-weighted sequences: increased visibility of the deep vas- cular network in the basal ganglia and white matter. Discussion Our patient had clinically asymptomatic GSD Ia that was fortuitously discovered after admission for acute ischemic stroke due to moyamoya disease (demonstrated 9 months later). The child was normoglycemic at the time of the stroke and during the subsequent TIA which occurred on the other side. Furthermore, he was able to tolerate prolonged fasting as previously observed in some patients with GSD Ia (5).No coagulation defect could be responsible for the stroke; thrornbocytemia was documented several times aRer the stroke but with increased bleeding time in favor of an hypocoagulatory state and dysfunction of platelets aggregation, as hequently encountered in this type of GSD in which bleeding tendency is a frequent manifestation (3).The cluld also had hyperlipemia and hypertriglyceridernia but the arterio- Fig. 2 Right carotid internal arteriography: stenosis of the carotid siphon with no flow through the right MCA and telangiectatic lenticulostriate arteries (moyamoya). The association of GSD Ia and moyamoya has been previously reported by Sunder in a 17-year-oldboy with acquired hemiplegia followed by TIA and severe stenosis of both carotid arteries with abundant collateral network of deep-penetrating vessels (11). Another child with acute hemiplegia and GSD type Ia has been reported by Fine et a1 (2).Although no arteriographicdemonstration was available, this patient might also have had moyamoya on clinical presentation with several episodes of arnaurosis suggestive of TIA following acute hemiplegia. The rarity of both conditions makes their association a non-fortuitous event and one must consider a relationship between them. In a GSD Ia kenage girl with pulmonary hypertension, Pizzo described anatomic vascular changes with medial hypertrophy and intimal fibrosis (10). These data have been recently confirmed (4). Similar pathologic findings have been described in cerebral vessels of patients with moyamoya (9), confinrung the hypothesis of a relationship between both conditions. Ciculaling vasoactive agents normally removed or altered by the liver might lead to a primary vasoconstrictive process (4, 10). Nevertheless, vascular changes are not usually recorded in GSD Ia, and patients with pulmonary hypertension had no neurological manifestations (4, 10). Furthermore, Pizzo reported that the brain was normal on postmortem examination (10).Although a very uncommon association, GSD Ia may be considered a possible cause for moyamoya and it would be justified to look for this arteriopaby in every child with GSD la and unexplained normoglycemic neurological deficits. References Carlson, C. B., E H.Harvey, I. Loop: Progressive alternating hemiplegia in early childhoodwith basal arterial stenosis and ndlangiecl&ia (moyamoya syndrome). Neurology 23 (1973) 734-744 Fine, R. N., R. Podasin, G. N . Donnel: Acute hemiplegia in glycogen storage disease type I. Acla Paediatr. Scand. 58 (1969) 621424 Gilchrist, C. S., R. N. Fine, G. N . Donnel: The hemostatic defect in glycogen storage disease type I. Acta Paediatr. Scand. 57 (1968) 205-208 Kishani, P., A. R. Bengun, Y. T.C h ~ nPulmonary : hypertension in glycogen storage disease type Ia. J. Inher Metab. Dis. 19 (1996) 212-216 Labrune, Ph., 1. Chalas, C. Baumn, M. Odihre: Prolonged fasting tolerance in two children with glycogen storage disease type Ia. J. Inher. Metab. Dis. 16 (1993) 1044-1045 Lee, PI.,D. S. Celmoje7, J. Robinson, S. Mc Corthy, D. 1. Betteridge, 1. !L Leonard: Hyperlipidaemia does not impair vaxular endothelial function in glycogen storage disease type la. Atherosclerosis 110 (1994) 9 5 1 0 0 Lei, K. I., C. J. Pan, L. L. Shelly, 1. L. Liw, 1. Y. Chon: Identification of mutations in the gene for glucose-6-phospbatase, the enzyme deficient in glycogen storage disease type la. J. Clin. Invest. 93 (1994) 1994-1999 Levin, S.: Moyamoya disease. Dev Med. Child Neurol. 24 (1982) 850-859 Nishirnoto, A., S. Takeuchi: Moyamoya disease. In: Irinken, PI., Bruyn, G .W.(Eds).Handbook of Clinical Neurology. Amsterdam, Elsevier North Holland Inc, 12 (1971) 352-383 'O P i m , C.].: Type I glycogen storage disease with focal nodular hyperplasia of the liver and vasoconstrictive pulmonary hypertension. Pediatrics 65 (1980) 341-343 I' Sunder, T.R.: Moyamoya disease in a patient with type I glycogenosis. Arch. Neurol. 38 (1981) 251-253 l2 Tamas, I.: Multiple progressive intracranial arterial occlusion : a syndrome of children and young adults. A.J.R. 106 (1969) 235-268 Neurologic Pbdiatrique Departement de Pkdiatrie HBpital des M a n t s Malades 149, rue de Skvres F-75743 Paris Cedex 15 h c e Downloaded by: Universite Laval. Copyrighted material. graphic findings were not those encountered in this situation and were typical of moyamoya disease (12). In connection with this, Lee et a1 (6) have shown that, in spite of hyperlipernia, vascular endothelial function was not impaired in GSD Ia patients.