Journal of Neuro-Ophthalmology, March 2013, Volume 33, Issue 1

Late Optic Neuropathy in Propionic Acidemia Following Surgical Intervention

Late Optic Neuropathy in Propionic Acidemia Following Surgical Intervention Traber et al (1) recently reported a case of "Subacute bilateral visual loss in methylmalonic acidemia" in a 23-year-old woman. Late-onset optic nerve damage has been described only rarely in organic acidemias. We present a similar case in propionic acidemia. A 24-year-old man diagnosed with propionic acidemia at birth had been controlled with strict observance of a low-propiogenic amino acid diet, medical treatment (enalapril, lansoprazole, tiamina, carnitine, and carvedi-lol), and prompt management of any acute metabolic decompensation. At the time of admission for elective vasectomy, the patient's chronic manifestations were mild developmental delay and cardiomyopathy. Surgery was performed under local anesthesia (mepivacaine and ropivacaine) with intravenous sedation. None of the drugs that have been described to cause problems in patients with propionic acidemia were used, and surgery was monitored by the patient's internist. Despite these precautions, the patient experienced transient hyperam-monemia (177 mmol/L), which was promptly controlled with carglumic acid and hydrocarbonated diet with no proteic components. After surgery, the patient complained of diminished vision, and on examination 2 months later, visual acuity was 20/160, right eye and counting fingers, left eye. He was unable to identify any of the pseudoisochromatic color plates. Ophthalmoscopic examination revealed bilateral optic disc pallor and, with optical coherence tomography, there was marked thinning bilaterally of the temporal retinal nerve fiber layer (Fig. 1). Magnetic resonance imaging (MRI) of the brain and orbits showed moderate parietal cortical atrophy bilaterally, hyperintense lesions involving the parietal periatrial white matter and reduced calibre of the optic chiasm (Fig. 2). Progressive and symmetric optic atrophy is a manifestation of several organic acidemias, including biotinidase deficiency (2-4), 3-methylglutaconic aciduria (Costeff syndrome) (5), methylmalonic aciduria and homocystinuria (CBL C disease) (6), and propionic acidemia. They all share a common path-ophysiologic mechanism of deficiency of mitochondrial enzymes involved in the catabolism of long-chain fatty acids and amino acids, leading to chronic metabolic decompensa-tion (7). The deficient enzyme in propionic acidemia is propionyl-CoA carboxylase, which is essential for the conver-sion of propionyl-CoA to methylmalonyl-CoA (8). To our knowledge, only 4 cases of propionic acidemia and optic nerve atrophy have been previously reported. Ianchulev et al (9) reported 3 boys (ages 2, 9, and 10 years) who developed optic atrophy, and Williams et al (10) described optic atrophy with visual dysfunction in a 20-year-old FIG. 1. Bilateral temporal optic disc pallor with absent foveal reflex is seen on funduscopy. Inset: Optical coherence tomography shows thinning of the temporal retinal nerve fiber layer (mm) in each eye. FIG. 2. A. Coronal fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging shows moderate parietal atrophy with periatrial white matter hyperintensities. B. T2 coronal scan demonstrates thinning of the optic chiasm (arrow). 90 Noval et al: J Neuro-Ophthalmol 2012; 33: 90-95 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. woman. In the last case, concomitant nutritional deficiency (vitamins B1 and B6) may have been responsible for the optic neuropathy because her vision stabilized with appropriate supplementation. In the case reported by Traber et al (1) MRI showed enhancement of both optic nerves. Their patient developed rapid onset of decreased vision, and the MRI was performed 2 weeks after the onset. In contrast, our patient's visual loss was more chronic, and MRI was obtained approximately 2 months after the onset of visual failure. We believe that the late occurrence of optic neuropathy in our patient may, in part, be the result of strict control of his disease since birth. Fasting, the stress of the surgical procedure, and hyperammonemia that developed during surgery may have triggered optic nerve damage. Susana Noval, PhD, MD Ophthalmology Department, La Paz University Hospital, IdiPaz, Madrid, Spain, [e-mail] Mónica López-Rodríguez, MD Internal Medicine Department, La Paz University Hospital, IdiPaz, Madrid, Spain Eugenia González-Sánchez, MD Ophthalmology Department, La Paz University Hospital, IdiPaz, Madrid, Spain Inés Contreras, PhD, MD Ophthalmology Department, Ramón y Cajal University Hospital, Madrid, Spain Arancha Royo, MD Radiology Department, La Paz University Hospital, IdiPaz, Madrid, Spain Ana Boto-De-los-Bueis, MD, PhD Ophthalmology Department, La Paz University Hospital, IdiPaz, Madrid, Spain The authors report no conflicts of interest. REFERENCES 1. Traber G, Baumgartner MR, Schwarz U, Pangalu A, Donath MY, Landau K. Subacute bilateral visual loss in methylmalonic acidemia. J Neuroophthalmol. 2011;31:344-346. 2. Salbert BA, Astruc J, Wolf B. Ophthalmologic findings in biotinidase deficiency. Ophthalmologica. 1993;206:177-181. 3. Rahman S, Standing S, Dalton RN, Pike MG. Late presentation of biotinidase deficiency with acute visual loss and gait disturbance. Dev Med Child Neurol. 1997;39:830-831. 4. Puertas Bordallo D, Martin Reyes C, Ruiz-Falcó Rojas ML, Duat Rodríguez A, Valls Ferrán MI. [Optic neuropathy in biotinidase deficiency]. Arch Soc Esp Opthalmol. 2004; 79: 393-396. 5. Costeff H, Elpeleg O, Apter N, Divry P, Gadoth N. 3-Methylglutaconic aciduria in "optic atrophy plus". Ann Neurol. 1993;33:103-104. 6. Patton N, Beatty S, Lloyd IC, Wraith JE. Optic atrophy in association with cobalamin C (cblC) disease. Ophthalmic Genet. 2000;21:151-154. 7. Wolf B, Hsia YE, Sweetman L, Gravel R, Harris DJ, Nyhan WL. Propionic acidemia: a clinical update. J Pediatr. 1981;99: 835-846. 8. Harker HE, Emhardt JD, Hainline BE. Propionic acidemia in a four-month-old male: a case study and anesthetic implications. Anesth Analg. 2000;91:309-311. 9. Ianchulev T, Kolin T, Moseley K, Sadun A. Optic nerve atrophy in propionic acidemia. Ophthalmology. 2003;110: 1850-1854. 10. Williams ZR, Hurley PE, Altiparmak UE, Feldon SE, Arnold GL, Eggenberger E, Mejico LJ. Late onset optic neuropathy in methylmalonic and propionic acidemia. Am J Ophthalmol. 2009;147:929-933. Is Pentoxifylline Plus Vitamin E an Effective Treatment for Radiation-Induced Optic Neuropathy? We read with great interest the article, "Novel treat-ment of radiation optic neuropathy with intravenous bevacizumab" by Farooq et al (1). We recently evaluated a patient with radiation optic neuropathy (RON) who also experienced dramatic visual recovery after treatment with corticosteroids, pentoxifylline, and vitamin E. A 42-year-old woman reported acute, painless loss of vision in the right eye 3.5 months following gamma knife therapy for a partially resected pituitary tumor. Treatment consisted of 23 Gy to the right sellar region in a single treatment, with the right optic nerve receiving a marginal point maximum dose of 10.5 Gy (Fig. 1A). Visual acuity was counting fingers in the right eye and 20/20 in the left eye, with a right relative afferent pupillary defect. Automated visual field testing demonstrated dense, global field loss in the right eye (Fig. 2A) and was normal in the left eye. The remainder of the examination, including ophthalmoscopy, was unremarkable. Magnetic resonance imaging of the brain revealed en-hancement of the canalicular segment of the right optic nerve (Fig. 1B). Cerebrospinal fluid analysis and serologic studies to rule out demyelinating, infectious, and autoimmune causes were normal. Thought to have RON, the patient was treated with 6 mg of dexamethasone, 400 mg of pentoxifylline, and 400 IU of vitamin E, each given 3 times per day. Two weeks after initiating therapy, the patient reported a dramatic improvement in her vision. Visual acuity was 20/40 in the right eye, with marked improvement in her right visual field (Fig. 2B). She was tapered off dexa-methasone over 6 weeks but continued on pentoxifylline and vitamin E. Chahal et al: J Neuro-Ophthalmol 2012; 33: 90-95 91 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.