Article Text

Delayed diagnosis of homocystinuria as a cause of vascular retinal occlusion in young adults
  1. ELZBIETA W MOLICKA,
  2. HENK VAN SLOOTEN
  1. Diaconessenhuis Leiden, Netherlands
  2. FC Donders Institute, Academic Hospital Utrecht, Netherlands
  3. Diaconessenhuis Leiden, Netherlands and Department of Ophthalmology, Free University, Amsterdam, Netherlands
  1. ALLEGONDA VAN DER LELIJ
  1. Diaconessenhuis Leiden, Netherlands
  2. FC Donders Institute, Academic Hospital Utrecht, Netherlands
  3. Diaconessenhuis Leiden, Netherlands and Department of Ophthalmology, Free University, Amsterdam, Netherlands
  1. MARIA S A SUTTORP-SCHULTEN
  1. Diaconessenhuis Leiden, Netherlands
  2. FC Donders Institute, Academic Hospital Utrecht, Netherlands
  3. Diaconessenhuis Leiden, Netherlands and Department of Ophthalmology, Free University, Amsterdam, Netherlands
  1. Dr M S A Suttorp-Schulten, MD, Department of Ophthalmology, Free University Hospital Amsterdam, PO Box 7057, 1007 MB Amsterdam, Netherlands

Statistics from Altmetric.com

Editor,—Retinal vascular occlusions in young adults are seen very infrequently and are generally associated with systemic disorders.1 Diagnosis of the underlying disease is very important because of treatment and prevention of recurrence.2 We report two cases initially presenting with systemic neurological disease. Both developed retinal vascular occlusions and the diagnosis of the underlying cause was only made afterwards.

CASE REPORTS

A 30 year old, obese woman presented to the neurologist with acquired perceptive deafness, a tetrapyramidal syndrome, with gait problems and urinary incontinence. Multiple sclerosis was considered, but cerebral magnetic resonance imaging scan showed only atypical lesions. Symptoms gradually decreased without disappearing completely. Six months later an occlusion of the retinal nasal inferior artery occurred in the right eye, visual acuity was 20/20 in both eyes (Fig 1). Haematological evaluation revealed a disturbed determination of peak levels of homocysteine after oral loading with methionine, suggesting homocystinuria causing thromboembolic processes in the cerebrum and in the eye. Repeated determination after oral loading with methionine after vitamin B12 treatment was still disturbed, confirming the diagnosis of homocystinuria. The patient was treated with pyridoxine and acetylsalicylic acid. Two out of four of the patient’s sisters were also found to suffer from homocystinuria.

Figure 1

Early phase fluorescein angiography of right eye of patient 1, showing occlusion of the retinal nasal inferior artery.

A 23 year old obese female, who smoked and had used contraceptives, underwent caesarean section because of negative discongruency and breech presentation. Postoperatively, thrombophlebitis of the arm and erythema nodosum of the legs developed. Four weeks later visual acuity in the left eye deteriorated, caused by massive occlusive retinal vasculitis, retinal haemorrhages, papillitis, and massive retinal oedema with Roth spots (Fig 2). A biopsy of the skin lesions of the leg showed leucoclastic vasculitis. Further investigation could not reveal the underlying cause. Treatment with clindamycin, acetylsalicylic acid, and methylprednisolone was started and panretinal laser therapy was performed. Four months after treatment was completed, the other eye developed retinal haemorrhages and occlusion of the upper, temporal branch of the main retinal vein.

Figure 2

Fluorescein angiography of right eye of patient 2, showing massive occlusive retinal vasculitis, papillitis, retinal haemorrhages, and massive retinal oedema and Roth spots.

Analysis showed elevated peak levels of homocysteine after loading with methionine, suggesting homocystinuria. Analysis of DNA and cystathionine β synthetase in the cultured fibroblasts confirmed the diagnosis of homocystinuria. Treatment with acetylsalicylic acid, folic acid, and pyridoxine resulted in the normalisation of the homocysteine level. The visual acuity 1 year after the first event was 20/15 and 20/50 in the right eye and left eye, respectively.

COMMENT

Homocystinuria consists of a group of different metabolic disorders, all resulting in elevated levels of homocysteine in blood and urine. The most important is the cystathionine β synthetase reduction. Homocysteine interferes with crosslinking of collagen resulting in disturbances in the endothelial synthesis. Also there is an increased platelet adhesion causing thrombotic occlusive disease. The vascular complications led to occlusion of coronary, renal, and cerebral arteries and veins.3

The most frequent manifestations in homozygous patients are disorders of the lens (ectopia 85%, microspherophakia), mental retardation, cardiovascular defects, and skeletal changes.4 5 Retinal vascular occlusion is an infrequent manifestation of homocystinuria.5-7

The homozygotic form leads to very early vascular disease with early death and the above mentioned manifestations. Heterozygotic carriers (1:70 in general population) are at risk for occlusive vascular disease at a young age. This can often be prevented by treatment with low doses of acetylsalicylic acid, pyridoxine, and sometimes folic acid.3 Factors suggesting other causes of thromboembolism (pregnancy, obesity, oral contraceptives) can delay the diagnosis of homocystinuria and successful treatment.2

In conclusion, homocystinuria should be considered in cases of young adults with retinal vascular occlusions, even if there are no other ocular abnormalities—for example, ectopia lentis. The possible sequelae for general health should be of concern when evaluating and treating these patients.

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.