J Neurosurg (2 Suppl Pediatrics) 107:167–172, 2007
Glutaric acidemia type I: a neurosurgical perspective Report of two cases LEWIS C. HOU, M.D.,1 ANAND VEERAVAGU, B.S.,1 ANDREW R. HSU, B.S.,1 GREGORY M. ENNS, M.D.,2 AND STEPHEN L. HUHN, M.D.1 Departments of 1Neurosurgery and 2Pediatrics–Genetics, Stanford University School of Medicine, Stanford, California
PGlutaric acidemia type I (GA-I) is a rare, autosomal recessive metabolic disorder that leads to severe dystonia, basal ganglia degeneration, and bilaterally enlarged anterior middle cranial fossae. The current management of this disease includes early diagnosis with newborn screening, prevention of catabolism, carnitine supplementation, and a strict dietary protein restriction. Neurosurgical evaluation and intervention may be necessary in patients with structural lesions associated with this disease. In this report, the authors present two pediatric patients with GA-I and discuss the neurosurgical aspects of this rare medical disorder. (DOI: 10.3171/PED-07/08/167) KEY WORDS • arachnoid cyst • dystonia • glutaric acidemia • glutaryl-CoA dehydrogenase • hydrocephalus • subdural hemorrhage
acidemia type I is an autosomal recessive disorder caused by GCDH deficiency. This enzyme deficiency results in increased retention of GA in the blood, urine, and CSF. Patients generally present between the ages of 6 and 18 months with a variety of distinct signs and symptoms including intracranial fluid collection, dystonia, and macrocephaly. A possible association between GAI and intracranial arachnoid cysts has also been described.9 Although GA-I screening for newborns, using tandem mass spectrometry, is available in most states, it is likely that, in some patients with GA-I who excrete low amounts of the characteristic diagnostic metabolites, the disorder may go undiagnosed until the onset of their first catabolic crisis.7 Patients may also present with a variety of neurological sequelae related to the disorder, and subsequently undergo metabolic screening and evaluation. We report on two cases of GA-I and discuss the associated neurosurgical management, clinical presentations, and imaging findings. Early diagnosis and preventative therapy are key to maintaining a favorable outcome in patients diagnosed with GA-I. Understanding the root cause of various neurological symptoms is important for appropriate neuro-
G
LUTARIC
Abbreviations used in this paper: CSF = cerebrospinal fluid; CT = computed tomography; GA = glutaric acid; GA-I = glutaric acidemia type I; GCDH = glutaryl-CoA dehydrogenase; ICP = intracranial pressure; MR = magnetic resonance; 3-OH-GA = 3-hydroxyglutaric acid.
J. Neurosurg: Pediatrics / Volume 107 / August, 2007
surgical intervention, particularly because acute invasive procedures may exacerbate the ongoing metabolic crisis and actually increase the risk of further basal ganglia degeneration. Case Reports Case 1
This 36-month-old male fraternal twin was born at 31 weeks’ gestation via cesarean section after preterm labor. An ultrasonography study of the patient’s head was obtained after he was born and revealed a stable Grade I germinal matrix hemorrhage. When he was 3 months of age, progressive macrocephaly developed and the diagnosis of communicating hydrocephalus was made based on the prominence of extraaxial fluid. Although the child had reached appropriate developmental milestones, his parents reported mild generalized muscle weakness. When he was 6 months of age, the patient was admitted to another institution for hypotonia, persistent emesis, concurrent back arching and decorticate-like posturing. Despite maximal supportive treatment, the patient’s inconsolable state and dystonia persisted. He received a subdural–peritoneal shunt at the secondary institution because of concerns that these symptoms were related to progression of hydrocephalus. No improvement in symptoms was reported after shunt placement. A subsequent MR image of the brain dem167
L. C. Hou et al. onstrated diffuse white matter changes and bilateral, enlarged middle fossa subarachnoid spaces (Fig. 1A and B). The findings on MR imaging prompted a metabolic evaluation that revealed elevated levels of GA and 3-OH-GA in his urine consistent with a diagnosis of GA-I. A review of the patient’s family history was unremarkable for consanguinity or known relatives with this metabolic disease. The results of DNA testing showed that the patient had compound heterozygosity for the R128Q and R313W mutations. The patient was treated with a low-protein diet involving carnitine and riboflavin supplementation and a specifically reduced intake of tryptophan and lysine. Baclofen, trihexyphenidyl, and diazepam were prescribed to improve his dystonic symptoms. The patient presented to the pediatric neurosurgical service after transfer of care from the metabolic clinic at our institution, where he was followed up for the management of his macrocephaly and subdural–peritoneal shunt. When he was 11 months of age, the child’s parents reported mild improvement in his head and hand control; however, he had not demonstrated the ability to sit independently, nor had he made any attempt to crawl or stand. At 25 months of age, the patient continued to have poor head and trunk control; he was able to vocalize vowel and consonant sounds, but had not yet spoken any words. The patient had been admitted to the hospital on multiple occasions for lethargy, emesis, and hypotonia secondary to dehydration. Corresponding head CT scans demonstrated stable but severe generalized parenchymal volume loss, particularly in the frontal and temporal lobes (Fig. 1C and D). Case 2
This 31-month-old boy was born after 38 weeks of gestation via vacuum-assisted delivery. At 1 month of age, his head circumference measured in the 95th percentile, and progressed to greater than the 97th percentile in the next 6 months. On MR imaging a significant bilateral subacute and chronic frontoparietal subdural hematoma was demonstrated (Fig. 2A and B). Prominent bilateral sylvian fissures and bilateral basal ganglia signal abnormalities were also noted. When he was 9 months of age, the time of referral, the patient had no obvious neurological deficits or developmental delays. He demonstrated good head control and was able to pull himself up to a standing position with support. Consultation with an ophthalmologist confirmed the absence of retinal hemorrhages, and nonaccidental trauma was excluded from the diagnosis. A genetics consult was obtained to evaluate for suspected underlying metabolic abnormalities. Urine organic acid studies demonstrated the presence of 3-OH-GA and an elevated level of GA consistent with GA-I. The patient was immediately placed on an appropriate diet regimen and received carnitine and riboflavin supplements. The subdural hematoma (Fig. 2C and D) was evacuated through bilateral bur holes. The patient tolerated the procedure without complications, and the postoperative CT scan revealed near resolution of the subdural hematoma (Fig. 2E). Two months postoperatively, the patient was found to have a new subacute subdural fluid collection on the right side, suggestive of an interval hemorrhage (Fig. 2F). There was no interval history of trauma, and it was believed that the second hemorrhage was most likely related to the risks associated with an enlarged extraaxial space. The 168
FIG. 1. Case 1. A: Axial T2-weighted MR image demonstrating bilaterally enlarged sylvian fissures and atrophic frontal and temporal parenchyma. B: Corresponding axial fluid attenuated inversion recovery image. C: Persistent widened sylvian fissures are visible on CT scan. D: Bilaterally enlarged CSF space extends to the anterior middle fossa on CT scanning.
subdural hematoma was monitored without intervention, and subsequent CT scans demonstrated its complete resolution (Fig. 2G and H). Discussion Glutaric acidemia type I is an autosomal recessive disorder involving GCDH, a catalyst in the oxidative decarboxylation of glutaryl-CoA. Mutations in the gene for GCDH result in dysfunctional metabolism of the amino acids lysine, hydroxylysine, and tryptophan.5,8,19,23,30 The lack of functional GCDH activity leads to an accumulation of GA, 3-OHGA, and glutaconic acid in the blood, urine, CSF, and brain parenchyma, with the level of 3-OH-GA one or two orders of magnitude higher than normal.5,37 The combined worldwide frequency of GA-I, based on newborn screening by electrospray ionization random mass spectrometry, is one in 100,000 infants.11 Approximately 400 to 500 patients have been identified worldwide, with the highest prevalence (1:300 to 1:400 newborns) in the Amish community of Lancaster County, Pennsylvania, and among North American aboriginals (Ojibway-Cree tribe) in a genetically isolated community in northeastern Manitoba and northwestern Ontario in central Canada.10 Children with symptomatic GA-I may present during their first year of life with a wide range of neurological abnormalities.22,23,29,31,39,42 Neurological signs include dystonia, severe irritability, loss of developmental milestones, and cognitive dysfunction. Imaging of the central nervous sysJ. Neurosurg: Pediatrics / Volume 107 / August, 2007
Glutaric acidemia Type I
FIG. 2. Case 2. Preoperative axial fluid attenuated inversion recovery MR imaging (A and B) and CT scans (C and D) demonstrating bilateral subdural hematomas of varying ages and classic bilateral widening of the sylvian fissures. E: Postoperative CT scan demonstrating decompression of the left lateral ventricle after bur hole drainage of the left subdural hematoma. F: Computed tomography scan showing subsequent spontaneous development of a new subdural hematoma in the right frontal region. G and H: Computed tomography scans demonstrating complete resolution of bilateral subdural fluid collections, which was achieved after conservative management. Dilated sylvian fissures persist, however.
tem may reveal degeneration of the basal ganglia, macrocephaly, subdural hematoma/extraaxial fluid collections, arachnoid cysts, and hydrocephalus. The central nervous system may be affected as early as the 30th week of gestation with hydrocephalus and macrocephaly.14 The functional disability in patients with GA-I correlates with the degree of basal ganglia degeneration.14,30,39 Some authors have hypothesized that GA and 3-OH-GA are excitotoxins that cause neurodegeneration via glutamate receptor overstimulation.25 It has been suggested that when patients with GA-I present with an acute encephalopathy crisis, their symptoms resemble a “metabolic stroke” rather than cerebral vascular occlusion. Metabolic stroke in patients with GA-I involves the rapid loss of selective neuronal function caused by metabolic disarray rather than stroke secondary to ischemia.5 In their study of 77 patients, Strauss and colleagues39 concluded that this metabolic stroke, caused by acute striatal necrosis, is the most debilitating manifestation of GA-I, and is the major determinant of both morbidity and death. Furthermore, patients with GA-I also have an increased risk of subdural hematoma (as seen in Case 2). Therefore, in addition to presenting with the metabolic stroke syndrome, these patients may also present with neurological symptoms related to intracranial extraaxial hemorrhage.32,42 The diagnosis of GA-I is often made in the setting of evaluation for other disorders. Due to the disorder’s close association with subdural and retinal hemorrhages, patients with GA-I are sometimes initially suspected as victims of nonaccidental injuries.3,6,20,33,41,42 Indeed, the concern for possible inflicted injuries was the cause for the initial referral of the patient in Case 2. The pathogenesis of subdural hematomas and associated retinal hemorrhages remains unclear. The increased frequency of subdural hematomas observed in paJ. Neurosurg: Pediatrics / Volume 107 / August, 2007
tients with GA-I is frequently hypothesized as due to the expanded extraaxial CSF spaces that result in stretching of the bridging cortical veins.42 Consequently, patients are prone to developing subdural hemorrhages after minor head injuries and have higher risks for hematoma recurrences.14 Retinal hemorrhages associated with GA-I, although less frequently reported in the literature, can also further complicate its distinction from nonaccidental trauma. In a review of 57 patients with GA-I, Hoffmann et al.12 reported that 20 to 30% had chronic subdural effusions, which were accompanied by retinal hemorrhages. Although several hypotheses exist as to the mechanism by which retinal hemorrhages occur, some stipulate that the sudden increase in intracranial venous pressure associated with acute bleeding can cause retinal hemorrhages.38 Others postulate that retinal hemorrhages may be associated with the increased ICP encountered during an acute encephalopathic crisis.17 Recent diagnostic criteria now indicate that while subdural and retinal hemorrhages are not pathognomonic for GA-I, they certainly heighten the suspicion of a possible underlying metabolic disorder.17,21 The rarity of GA-I and the initial patient presentation involving macrocephaly, subdural hemorrhage, or basal ganglia degeneration may result in delayed or even erroneous diagnoses. Currently, newborn screening using tandem mass spectrometry is an effective method for making a presymptomatic diagnosis of GA-I. However, due to the variability of disease phenotypes, some cases are likely to be missed, and a high suspicion of GA-I should be maintained during the evaluation of dystonia or macrocephaly in children.34,36,41 False negative results may occur in rare patients that excrete normal or slightly elevated levels of GA resulting in normal levels of glutarylcarnitine in blood samples.7,24 Prospective and retrospective analyses have shown that although new169
L. C. Hou et al. born screening with tandem mass spectrometry can identify low excretors, some patients will still remain undiagnosed unless an enzymatic assay and DNA mutational analysis are also performed.7 The quantification of glutarylcarnitine via urine analysis has recently been shown to be a sensitive diagnostic technique in the investigation of GA-I.40 Early identification and treatment of the child with asymptomatic GA-I are essential to a favorable clinical outcome.1 Prevention of encephalopathic crisis can aid in halting the onset of more devastating symptoms of GA-I. Current treatment strategies require a multidisciplinary approach including dietary supplements and restrictions, and potential neurosurgical intervention if indicated. Afflicted children should receive L-carnitine supplementation to maintain mitochondrial homeostasis.1 Dietary therapy involves restriction of foods rich in lysine and tryptophan.43 In cases of acute catabolic events, the rapid administration of high-calorie intravenous fluids containing glucose, intralipids, and carnitine, can effectively restore metabolic balance. One of the goals in this emergency scenario is to improve symptoms to the point that the child can eat normally, which further helps to reverse the catabolic state. Neuroimaging and GCDH Deficiency
Neuroimaging with CT scanning and/or MR imaging is a useful tool for the early diagnosis and evaluation of patients with GCDH deficiency.4 It is widely accepted that neuroimaging of patients with clinical symptomatology, must involve the evaluation of three major factors: 1) widening of sylvian fissures, 2) atrophic basal ganglia lesions, and 3) white matter lesions.18,41 In a study of 14 patients with GAI, Twomey et al.41 noted that imaging studies revealed bilateral widening of the sylvian fissures in 93% of patients. Postmortem pathological findings revealed corresponding acute striatal necrosis with loss of medium-sized neurons in the striatum of the dorsal caudate, ventral caudate, and the dorsal and ventral putamen.5,30 Common imaging findings include the characteristic “bat wing” appearance of the frontotemporal region secondary to the large extraaxial spaces lateral to the frontal and temporal lobes.27,42 The combination of frontoopercular–temporal hypoplasia and communicating hydrocephalus is considered pathognomonic for GAI.39 Diffusion weighted MR imaging is a useful method for assessing the extent of basal ganglia degeneration, including the putamen, in patients with GCDH deficiency.4 The results of MR imaging may prompt a metabolic and genetic workup, and thus early dietary restriction.35 Increased signal intensities on T2-weighted MR images with preserved volumes within both caudate heads and lentiform nuclei are often the first presenting findings. Although these characteristics may represent hallmarks of the disease, findings on imaging are highly variable and should always be combined with a comprehensive metabolic evaluation, including GCDH enzyme quantification and/or DNA analysis.35 Neurosurgical Management of GA-I
Patients with GA-I are often referred to the neurosurgical service for macrocephaly or for further evaluation after abnormal imaging findings. Imaging studies may reveal subdural fluid collection, ventriculomegaly, widening of the sylvian fissures, and basal ganglia signal abnormalities.9,10 170
As mentioned earlier, the finding of unexplained subdural hemorrhage may raise concerns of nonaccidental injury, and thus child abuse assessments are often initiated. In this circumstance, the neurosurgeon may be called on to assess the relationship of intracranial abnormalities to that of the clinical status of the patient. Early recognition of patients with GA-I is critical for avoiding not only the ramifications of misdiagnosis, but also to ensure that proper treatments are initiated promptly.41 Neurosurgeons should therefore exert judicious care in assessing patients with atypical subdural hemorrhage, particularly when such collections are chronic, and imaging studies reveal other underlying cerebral abnormalities or hypoplasia. The decision to undertake subdural hematoma drainage in patients with GA-I should be made on a case-to-case basis. Similar to hematomas related to other causes, indications for surgery include radiographic evidence of progression and mass effect accompanied by worsening of clinical symptoms. In patients with GA-I however, clinical symptoms associated with the neurodegenerative process often overlap with symptoms from increased ICP, making this determination more difficult. Furthermore, the consideration for potential hematoma recurrence (as demonstrated in Case 2) must be included in the management algorithm, and the patient and family should be informed of this possibility. Although one of the most common presenting symptoms of patients with GA-I is macrocephaly, which presents at birth or develops within the first 6 months of life, its treatment approach remains controversial due to unclear and potentially multifactorial underlying causes.10,12,29 Some authors have concluded that subdural hematomas are the cause of macrocephaly in their patients; other potential causes include hydrocephalus, arachnoid cysts, and diffuse cerebral edema.2,9,13,15 For example, Hoffmann et al.12 have suggested that subdural hygromas and hematomas are rarely associated with increased ICP and shunt placement does not result in reexpansion of cerebral tissue. On the other hand, anecdotal reports in the literature suggest that a subset of patients may benefit from ventriculoperitoneal shunt implantation. Martinez-Lage and associates28,29 reported on two siblings with GA-I who showed evidence of clinical worsening when their shunts malfunctioned and emphasized that assessment of patients with GA-I should include ICP measurements. At this time, it remains controversial whether persistent and progressive elevated ICP is part of the natural history of disease progression in all patients with GA-I. Therefore, treatment with CSF diversion must include careful and objective assessment for signs of increased ICP and analysis of direct measurements. An association between bilateral arachnoid cysts and GA-I has been recognized; however, convincing radiological or surgical evidence confirming a true relationship is rare.9 Jamjoom et al.16 reported the use of cystoperitoneal shunts in the first case of surgically confirmed bilateral arachnoid cysts in female siblings with GA-I. In one of the cases described, surgical intervention included placement of a cystoperitoneal shunt that resulted in reduction of the arachnoid cyst size and disappearance of midline shift. The unusual nature of GA-I not only results in a diagnostic and treatment dilemma, but the underlying metabolic disorder also warrants further consideration in the decision to undertake any surgical intervention. Surgery in patients with GA-I may be complicated by the possibility that the J. Neurosurg: Pediatrics / Volume 107 / August, 2007
Glutaric acidemia Type I stress of an operative intervention and intravenous amino acid administration may induce a catabolic state that would exacerbate the patient’s condition and result in additional striatal damage.14,26 Because of this potential complication, effective communication with the genetics and pediatric services preoperatively and the anesthesiologists intraoperatively is crucial to ensure optimal treatment and outcome. Any surgical treatment of children with GA-I therefore requires a synergistic approach that addresses both the urgency of the neurosurgical disorder and the underlying metabolic dysfunction. Conclusions Patients with GA-I often manifest neurological symptoms or radiographic findings that warrant further surgical investigation and treatment. The intracranial abnormality is best approached by understanding the spectrum of dysfunction that can result from GCDH deficiency. By obtaining diagnostic metabolic laboratory tests in children who display the characteristics of GA-I, clinicians may prevent the onset of more severe symptoms and obviate further CNS degeneration. Characteristic changes in brain anatomy, including hydrocephalus, cerebral hypoplasia, and subdural hemorrhage, may require thoughtful neurosurgical assessment prior to intervention. Acknowledgments Dr. Hou and Dr. Veeravagu contributed equally to this study. References 1. Baric I, Zschocke J, Christensen E, Duran M, Goodman SI, Leonard JV, et al: Diagnosis and management of glutaric aciduria type I. J Inherit Metab Dis 21:326–340, 1998 2. Bergman I, Finegold D, Gartner JC Jr, Zitelli BJ, Claassen D, Scarano J, et al: Acute profound dystonia in infants with glutaric acidemia. Pediatrics 83:228–234, 1989 3. Bishop FS, Liu JK, McCall TD, Brockmeyer DL: Glutaric aciduria type 1 presenting as bilateral subdural hematomas mimicking nonaccidental trauma. J Neurosurg 106 (3 Suppl Pediatrics):222–226, 2007 4. Desai NK, Runge VM, Crisp DE, Crisp MB, Naul LG: Magnetic resonance imaging of the brain in glutaric acidemia type I: a review of the literature and a report of four new cases with attention to the basal ganglia and imaging technique. Invest Radiol 38:489–496, 2003 5. Funk CB, Prasad AN, Frosk P, Sauer S, Kolker S, Greenberg CR, et al: Neuropathological, biochemical and molecular findings in a glutaric acidemia type 1 cohort. Brain 128:711–722, 2005 6. Gago LC, Wegner RK, Capone A Jr, Williams GA: Intraretinal hemorrhages and chronic subdural effusions: glutaric aciduria type 1 can be mistaken for shaken baby syndrome. Retina 23:724–726, 2003 7. Gallagher RC, Cowan TM, Goodman SI, Enns GM: GlutarylCoA dehydrogenase deficiency and newborn screening: retrospective analysis of a low excretor provides further evidence that some cases may be missed. Mol Genet Metab 86:417–420, 2005 8. Goodman SI, Stein DE, Schlesinger S, Christensen E, Schwartz M, Greenberg CR, et al: Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations. Hum Mutat 12:141–144, 1998 9. Hald JK, Nakstad PH, Skjeldal OH, Stromme P: Bilateral arachnoid cysts of the temporal fossa in four children with glutaric aciduria type I. AJNR Am J Neuroradiol 12:407–409, 1991
J. Neurosurg: Pediatrics / Volume 107 / August, 2007
10. Haworth JC, Dilling LA, Seargeant LE: Increased prevalence of hereditary metabolic diseases among native Indians in Manitoba and northwestern Ontario. CMAJ 145:123–129, 1991 11. Hedlund GL, Longo N, Pasquali M: Glutaric acidemia type 1. Am J Med Genet C Semin Med Genet 142:86–94, 2006 12. Hoffmann GF, Athanassopoulos S, Burlina AB, Duran M, de Klerk JB, Lehnert W, et al: Clinical course, early diagnosis, treatment, and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuropediatrics 27:115–123, 1996 13. Hoffmann GF, Trefz FK, Barth PG, Bohles HJ, Biggemann B, Bremer HJ, et al: Glutaryl-coenzyme A dehydrogenase deficiency: a distinct encephalopathy. Pediatrics 88:1194–1203, 1991 14. Hoffmann GF, Zschocke J: Glutaric aciduria type I: from clinical, biochemical and molecular diversity to successful therapy. J Inherit Metab Dis 22:381–391, 1999 15. Iafolla AK, Kahler SG: Megalencephaly in the neonatal period as the initial manifestation of glutaric aciduria type I. J Pediatr 114:1004–1006, 1989 16. Jamjoom ZA, Okamoto E, Jamjoom AH, al-Hajery O, Abu-Melha A: Bilateral arachnoid cysts of the sylvian region in female siblings with glutaric aciduria type I. Report of two cases. J Neurosurg 82:1078–1081, 1995 17. Kafil-Hussain NA, Monavari A, Bowell R, Thornton P, Naughten E, O’Keefe M: Ocular findings in glutaric aciduria type 1. J Pediatr Ophthalmol Strabismus 37:289–293, 2000 18. Kimura S, Hara M, Nezu A, Osaka H, Yamazaki S, Saitoh K: Two cases of glutaric aciduria type 1: clinical and neuropathological findings. J Neurol Sci 123:38–43, 1994 19. Koeller DM, Woontner M, Crnic LS, Kleinschmidt-DeMasters B, Stephens J, Hunt EL, et al: Biochemical, pathologic and behavioral analysis of a mouse model of glutaric acidemia type I. Hum Mol Genet 11:347–357, 2002 20. Kohler M, Hoffmann GF: Subdural haematoma in a child with glutaric aciduria type I. Pediatr Radiol 28:582, 1998 21. Kolker S, Christensen E, Leonard JV, Greenberg CR, Burlina AB, Burlina AP, et al: Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I). J Inherit Metab Dis 30:5–22, 2007 22. Kolker S, Koeller DM, Okun JG, Hoffmann GF: Pathomechanisms of neurodegeneration in glutaryl-CoA dehydrogenase deficiency. Ann Neurol 55:7–12, 2004 23. Kulkens S, Harting I, Sauer S, Zschocke J, Hoffmann GF, Gruber S, et al: Late-onset neurologic disease in glutaryl-CoA dehydrogenase deficiency. Neurology 64:2142–2144, 2005 24. Lindner M, Kolker S, Schulze A, Christensen E, Greenberg CR, Hoffmann GF: Neonatal screening for glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis 27:851–859, 2004 25. Lund TM, Christensen E, Kristensen AS, Schousboe A, Lund AM: On the neurotoxicity of glutaric, 3-hydroxyglutaric, and trans-glutaconic acids in glutaric acidemia type 1. J Neurosci Res 77:143–147, 2004 26. Lutcherath V, Waaler PE, Jellum E, Wester K: Children with bilateral temporal arachnoid cysts may have glutaric aciduria type 1 (GAT1); operation without knowing that may be harmful. Acta Neurochir (Wien) 142:1025–1030, 2000 27. Mandel H, Braun J, el-Peleg O, Christensen E, Berant M: Glutaric aciduria type I. Brain CT features and a diagnostic pitfall. Neuroradiology 33:75–78, 1991 28. Martinez-Lage JF: Neurosurgical treatment for hydrocephalus, subdural hematomas, and arachnoid cysts in glutaric aciduria type 1. Neuropediatrics 27:335–336, 1996 29. Martinez-Lage JF, Casas C, Fernandez MA, Puche A, Rodriguez Costa T, Poza M: Macrocephaly, dystonia, and bilateral temporal arachnoid cysts: glutaric aciduria type 1. Childs Nerv Syst 10:198–203, 1994 30. Neumaier-Probst E, Harting I, Seitz A, Ding C, Kolker S: Neuroradiological findings in glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency). J Inherit Metab Dis 27:869–876, 2004
171
L. C. Hou et al. 31. Nyhan WL, Zschocke J, Hoffmann G, Stein DE, Bao L, Goodman S: Glutaryl-CoA dehydrogenase deficiency presenting as 3-hydroxyglutaric aciduria. Mol Genet Metab 66:199–204, 1999 32. Osaka H, Kimura S, Nezu A, Yamazaki S, Saitoh K, Yamaguchi S: Chronic subdural hematoma, as an initial manifestation of glutaric aciduria type-1. Brain Dev 15:125–127, 1993 33. Piatt JH Jr, Frim D: Glutaric aciduria type 1 and nonaccidental head injury. Pediatrics 109:554, 2002 34. Puffenberger EG: Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania. Am J Med Genet C Semin Med Genet 121:18–31, 2003 35. Santos CC, Roach ES: Glutaric aciduria type I: a neuroimaging diagnosis? J Child Neurol 20:588–590, 2005 36. Smith WE, Millington DS, Koeberl DD, Lesser PS: Glutaric acidemia, type I, missed by newborn screening in an infant with dystonia following promethazine administration. Pediatrics 107: 1184–1187, 2001 37. Stokke O, Goodman SI, Thompson JA, Miles BS: Glutaric aciduria; presence of glutaconic and beta-hydroxyglutaric acids in urine. Biochem Med 12:386–391, 1975 38. Strauss KA, Morton DH: Type I glutaric aciduria, part 2: a model of acute striatal necrosis. Am J Med Genet C Semin Med Genet 121:53–70, 2003
172
39. Strauss KA, Puffenberger EG, Robinson DL, Morton DH: Type I glutaric aciduria, part 1: natural history of 77 patients. Am J Med Genet C Semin Med Genet 121:38–52, 2003 40. Tortorelli S, Hahn SH, Cowan TM, Brewster TG, Rinaldo P, Matern D: The urinary excretion of glutarylcarnitine is an informative tool in the biochemical diagnosis of glutaric acidemia type I. Mol Genet Metab 84:137–143, 2005 41. Twomey EL, Naughten ER, Donoghue VB, Ryan S: Neuroimaging findings in glutaric aciduria type 1. Pediatr Radiol 33: 823–830, 2003 42. Woelfle J, Kreft B, Emons D, Haverkamp F: Subdural hemorrhage as an initial sign of glutaric aciduria type 1: a diagnostic pitfall. Pediatr Radiol 26:779–781, 1996 43. Yannicelli S, Rohr F, Warman ML: Nutrition support for glutaric acidemia type I. J Am Diet Assoc 94:183–188, 191, 1994
Manuscript submitted November 13, 2006. Accepted April 23, 2007. Address reprint requests to: Stephen L. Huhn, M.D., Department of Neurosurgery, Stanford University School of Medicine, Edwards, R211 Stanford, California 94305-5327. email:
[email protected].
J. Neurosurg: Pediatrics / Volume 107 / August, 2007
