I chose this review article about homocystinuria as it is a condition I had heard of but never seen clinically before. The article summarises the ocular manifestations of the condition quite nicely.   As it turns out, one of our patients now has a confirmed diagnosis of homocystinuria after the onset of his eye symptoms which is atypical (however, not rare) as it is usually detected at the newborn metabolic screening.

Homocystinuria is a metabolic congenital disorder caused by dysfunctional cystathione β‑synthase enzymes, resulting in elevated methione and homocysteine levels. It is an inherited autosomal recessive trait. Intellectual disability, high myopia, ectopia lentis, osetoporisis, and thromboembolic events are among the features which can develop. Children also often present with a Marfanoid appearance due to their skeletal abnormalities – however, the lenticular zonules in Marfan’s syndrome are usually stretched compared to absent zonules in homocystinuria. Lens subluxation highly prevalent in homocystinuria and other studies have stated that approximately 90% of patients will suffer from lens subluxation with the prevalence in <7 year olds being around 70%. This article stated that “75% of the affected patients die by the age of 30” although other articles I read suggest that the percentage is much lower, between 18-25% and death is usually caused by a thromboembolic event. The minimum worldwide prevalence of homocystinuria is estimated to be around 1 in 344,000 however this number is a minimum estimation as current tests only measure methione levels which are often still low in newborn infants.

Our patient first presented to us at 8 months old for a constant ET. Interestingly, strabismus is not associated with homocystinuria and appears incidental but his early eye examinations provide us with a detailed background as we know that he did not develop refractive error until later in life and anterior segments were healthy. He underwent squint surgery at age 5 then became a consecutive XT. We continued to monitor him regularly and at age 7, he was diagnosed with global learning difficulties along with balance, co-ordination and fine motor issues. He was also prescribed his first myopic prescription at age 7 (right -2.00Ds and left -2.75DS). Over the following 2 years, his myopia progressed to right -5.50DS and left -6.50DS – prior to this his vision was normal in both eyes (after patching to treat strabismic amblyopia) and he had no significant refractive error. It was acknowledged that his axial length measurements were not exceedingly high and did not correlate with his myopia. He was then discharged by our consultant ophthalmologist with progressive myopia to his community optometrist who then re-referred the patient at age 11 for bilateral subluxated lenses, which explained why his myopia was progressing despite stable axial length measurements.

He was referred to Paediatrics and investigated for Marfan’s vs homocystinuria. Genetics later confirmed homocystinuria and blood test results revealed exceedingly low vitamin B12 at <74pmol/L and markedly high homocysteine at 195 umol/L (5-15 umol/L is regarded as a normal level).

Our patient is now aphakic and achieving 6/12 and 6/9.5 VA’s with correction. He is also now on pyridoxine. The article briefly describes the various conservative management options available to treat lens subluxation but also acknowledged that ultimately most patients will require a lensectomy.

It was identified that his significantly progressive myopia in the absence of axial length increase was unusual and although anterior segment examination was normal at the time, this case served as a reminder to remain vigilant. Often we see cases of seemingly isolated progressive myopia while we are treating their amblyopia or monitoring their squint and we are very fortunate to work very closely with our paediatric optometrists at Counties so are able to monitor and manage these patients without a consultant ophthalmologist’s input. Although homocystinuria is rare, I will now certainly think a bit more thoroughly if there are an unusual presentations of myopia.