Article Text

PDF

Late onset of Leber’s hereditary optic neuropathy in HIV infection
  1. CHRISTOPH LÜKE
  1. Klinik und Poliklinik für Augenheilkunde
  2. Klinik I für Innere Medizin, Universität Köln, Germany
  3. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  4. Molekulargenetisches Labor, Universitätsaugenklinik Tübingen, Germany
  5. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  1. OLIVER A CORNELY
  1. Klinik und Poliklinik für Augenheilkunde
  2. Klinik I für Innere Medizin, Universität Köln, Germany
  3. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  4. Molekulargenetisches Labor, Universitätsaugenklinik Tübingen, Germany
  5. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  1. JULIA FRICKE,
  2. ELFI LEHRER,
  3. KARL ULRICH BARTZ-SCHMIDT
  1. Klinik und Poliklinik für Augenheilkunde
  2. Klinik I für Innere Medizin, Universität Köln, Germany
  3. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  4. Molekulargenetisches Labor, Universitätsaugenklinik Tübingen, Germany
  5. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  1. BERND WISSINGER
  1. Klinik und Poliklinik für Augenheilkunde
  2. Klinik I für Innere Medizin, Universität Köln, Germany
  3. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  4. Molekulargenetisches Labor, Universitätsaugenklinik Tübingen, Germany
  5. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  1. RICHARD BRUNNER
  1. Klinik und Poliklinik für Augenheilkunde
  2. Klinik I für Innere Medizin, Universität Köln, Germany
  3. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  4. Molekulargenetisches Labor, Universitätsaugenklinik Tübingen, Germany
  5. Klinik und Poliklinik für Augenheilkunde, Universität Köln, Germany
  1. Christoph Lüke, Klinik und Poliklinik für Augenheilkunde, Universität Köln, Joseph-Stelzmann Strasse 9, D-50924 Köln, Germany

Statistics from Altmetric.com

Editor,—We report a case of late onset of Leber’s hereditary optic neuropathy (LHON) in a 59 year old patient with HIV infection being treated long term since 1991 with zidovudine. The onset and course of the patient’s eye disease as well as the diagnostic process were analysed. Molecular genetic testing revealed the mitochondrial DNA (mtDNA) mutation in nucleotide position 11778 confirming the diagnosis of LHON. In our patient late disease expression may be interpreted as a result of the rare combination of the 11778 mutation with HIV infection and long term zidovudine treatment. This is the first report on a patient with LHON suffering from additional HIV infection.

CASE REPORT

A 59 year old white man was admitted to our outpatient department in July 1997 with acute onset of vision loss in his left eye within the previous 2 weeks. The patient had been diagnosed with HIV infection in 1991. No opportunistic infections defining AIDS had been present so far. Antiretroviral therapy consisted of zidovudine since June 1991 as well as additional indinavir and nevirapine since January 1997. Best corrected visual acuity was right eye 20/20 and left eye 6/20. Further ophthalmic examination revealed a left afferent pupillary defect and an absolute central scotoma in the left eye. Indocyanine green angiography and fluorescein angiography disclosed a slight oedema of the optic disc without leakage. Visual evoked potentials (VEP) of the left eye showed reduced central amplitudes and prolonged latencies. Ophthalmic examination of the right eye at the time of presentation was normal.

The CD4+ T lymphocyte count was 360 cells ×106/l and HIV RNA in plasma was 8500 copies/ml. Neurological examination, including analysis of cerebrospinal fluid, was normal. Subsequent magnetic resonance imaging revealed normal cavernous sinuses and unremarkable optic nerves. No masses were seen in the orbits.

High dose steroid treatment on the basis of a presumptive diagnosis of optic neuritis could not prevent further progression of vision loss to hand movements in the patient’s left eye. In October 1997 the patient noticed similar symptoms in his right eye. Visual acuity was reduced to right eye 12/20.

On specific questioning the patient reported five male relatives—one of his brothers and four cousins—who had lost vision in early adulthood. Molecular genetic testing of a blood sample to investigate the presence of mitochondrial DNA (mtDNA) mutations yielded a mutation at position 11778, homoplasmic to the level of detection, confirming the diagnosis of Leber’s hereditary optic neuropathy (LHON). Therefore the patient was specifically asked for past or present additional medical or environmental factors postulated to trigger LHON. The patient denied any alcohol or tobacco consumption. Exposure to chemicals, toxins, or dangerous factory processes was not reported. Significantly larger amounts of foods with high cyanide content were not described. Additional metabolic or neurological diseases were not present.

COMMENT

LHON is a bilateral acute or subacute optic neuropathy caused by mutations in the mtDNA. Point mutations of the mtDNA at nucleotide position 11778, 3460, and 14484 involving NADH dehydrogenase (ND) subunits 1, 4, and 6, respectively, of respiratory chain complex I, are responsible for the majority of cases worldwide. These primary mitochondrial mutations are necessary but not sufficient for LHON disease expression. Only 30% of males and 10% of females carrying the 11778 mutation actually suffer visual loss.1 Therefore other genetic or epigenetic factors must play a role in disease penetrance although they are poorly defined at the present time. Proposed determinants of disease penetrance include heteroplasmy, secondary mitochondrial mutations, nutritional factors, metabolic disease, and toxic exposure.

Apart from the primary mutation our patient was only exposed to two epigenetic factors known to interfere with mitochondrial function. In previous studies HIV2 itself as well as zidovudine3-5 were demonstrated to affect mitochondrial integrity. Mitochondrial changes depend more on the duration of zidovudine application than on the applied dose.4 The onset of visual loss in LHON typically occurs between the ages of 15 and 35 years in most pedigrees. We hypothesise that the exceptionally long period of zidovudine treatment since diagnosis of HIV infection in 1991 and/or the infection itself may account for the unusual late expression of LHON in our patient. This is the first report on a patient with LHON suffering from additional HIV infection.

References

View Abstract

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.