Ectopia lentis with MoCo deficiency syndrome

Ectopia lentis or dislocated crystalline lens can be inherited or acquired. Inherited ectopia lentis can occur in a number of ways including familial where there is no association with systemic disease, in association with systemic disease such as in the case of Marfan's syndrome, or in metabolic disorders such as homocystinuria. The acquired condition may be due to a number of reasons, such as trauma, high myopia or hypermature cataract.1
Metabolic associations are extremely rare, for example the incidence of homocystinuria is said to be one in 344,000 worldwide although some areas have a higher incidence, Manchester being quoted as one in 85,000. However, homocystinuria does account for one in 20 cases of ectopia lentis. An even rarer metabolic disorder is reported in this short case study, that of molybdenum cofactor (MoCo) deficiency syndrome.
In 1998 there were 44 cases reported worldwide, today the figure is closer to 50. Many authors suggest that this condition does go unrecognised, with most of the reported cases being in Europe and the US, which probably represents an increased recognition of the condition in these countries.
MoCo deficiency syndrome is linked with the enzymes sulphite oxidase, xanthine dehydrogenase and aldehyde oxidase.
Typically, individuals present in the newborn period or in early infancy with intractable seizures and feeding difficulties. This condition is usually fatal, with death occurring by three years of age. However, some children do survive having severe developmental delay and neurological abnormalities.
This is the case for the sibling of the child reported in this study, whereas the patient herself was only found on biochemical analysis and cranial MRI, as the only reported problems were poor attention span and distractibility.2
She had, however, been noted to have dislocated lenses by her community optometrist. The reason for the characteristic dislocation of the crystalline lens is due to the alternative metabolic pathways that occur in this condition. Metabolites are substituted in connective tissue, which weaken the zonule of the lens.

Case report
Female patient aged 11
November 2000
The patient first presented with a history of visual difficulties at three to four years old. She was examined previously at an ophthalmology department and prescribed spectacles said to be:

R -18.50/+16.75x120; L -16.25/+15.50x65

The patient was not wearing spectacles. Unaided visions were found surprisingly to be 6/36 right and left. Ocular examination found bilateral subluxation of lenses up and out, with both lenses being clear and a few zonular fibres visible without dilation. The rest of the anterior segment examination was unremarkable as was the dilated fundus examination. Intraocular pressure was 12mmHg right and left.
Previously, the patient had tried soft contact lenses but encountered handling problems as she was too young. Retinoscopy was impossible through the phakic portion of the pupil so it was decided to correct the patient through the aphakic portion.

Refractive results were as follows:

R +18.50/-1.50 x 157.5 6/9, N6
L +19.50/-1.25 x 2.5 6/6+, N5

Spectacles were prescribed and dispensed.

March to December 2001
The patient was not wearing spectacles despite improved vision. At this point it was decided that contact lens fitting was an acceptable option.

Keratometry revealed:

R 8.50 along 5 L 8.40 along 175
8.15 along 95 8.00 along 5

There were no obvious contraindications to contact lens wear. Toric soft contact lenses were ordered from Contact Lens Precision Laboratories.

Specification:

R 9.10 14.30 +22.50/-2.00 x 148
L 9.00 14.30 +24.00/-1.50 x 15 GM3

Contact lens fit was found to be acceptable but visual acuities were only right 6/30 and left 6/40. At this point it was decided that spherical diagnostic lenses would be a sensible option in the fitting of this patient given the unexpected visual acuities and over-refraction results.

Final contact lens prescription was:

R 9.10 14.30 +19.50 6/6
L 9.00 14.30 +19.25 6/6

The lack of requirement for a cylindrical correction was put down to the centre thickness of the lens design and the material having a very low dehydration factor, thus giving a relatively 'rigid' soft lens that masked the corneal cylinder.
The lenses were considered to be acceptable to try, but it was felt that they would need to be modified as time went on. Further fitting was hampered by keratoconjunctivitis and excessive loss of lenses so it was not until the end of the year that the lenses were seen after any meaningful wearing time. At this point it was also suggested that a consultation regarding the possibility of lensectomies and intraocular implants should be obtained. The consultant ophthalmic surgeon who undertook this was unhappy to proceed in this case, so the patient was referred back for continued contact lens fitting.

January 2002 to date
Contact lens wear has been more successful during this period and the lenses have been modified to give improved fitting and stability to the visual acuity.
Also, material change has been made from GM3 to GM3 70 as both cornea showed early signs of hypoxia. The patient maintains a good level of acuity at right 6/9+ L 6/6 with no adverse corneal observations and a reasonable wearing time of eight hours a day.

Comments
The management of this case is not in itself any different than you would expect in any case of lens dislocation for whatever its cause, be it inherited or acquired.
When the lenticular dislocation is such that the border of the crystalline lens is causing considerable difficulty in prescribing a satisfactory spectacle prescription then the choice is to treat the patient as aphakic or refer for surgery, with the possibility of an intraocular implant.
What is interesting is the very rare underlying condition that led to this patient receiving HES treatment and in terms of contact lens practice, the soft lens material used masking the corneal astigmatism.
It is interesting to note that the patient's sibling who has profound neurological abnormalities has little by way of lens dislocation and only a minimal refractive error, so the degree of lens dislocation does not seem to relate to the severity of the MoCo deficiency syndrome.
What this patient shows is that, despite having the same phenotype as her sister, the condition which presented late at the age of six (indeed, it was late on even in her sister's case at one year of age) does have variable expression both in terms of neurological defects and in the severity of the ocular complications.

References
1 Kanski J. Clinical Ophthalmology Ð A Systematic Approach, 2nd edition. Oxford: Butterworth-Heinemann, 1989: 255-258.
2 Hughes E F, Fairbanks L et al. Molybdenum cofactor deficiency Ð phenotypic variability in a family with a late-onset variant. Developmental Medicine and Child Neurology, 1998; 40:57-61.

Steve Johns is principal optometrist at North Devon District HospitalEctopia lentis or dislocated crystalline lens can be inherited or acquired. Inherited ectopia lentis can occur in a number of ways including familial where there is no association with systemic disease, in association with systemic disease such as in the case of Marfan's syndrome, or in metabolic disorders such as homocystinuria. The acquired condition may be due to a number of reasons, such as trauma, high myopia or hypermature cataract.1
Metabolic associations are extremely rare, for example the incidence of homocystinuria is said to be one in 344,000 worldwide although some areas have a higher incidence, Manchester being quoted as one in 85,000. However, homocystinuria does account for one in 20 cases of ectopia lentis. An even rarer metabolic disorder is reported in this short case study, that of molybdenum cofactor (MoCo) deficiency syndrome.
In 1998 there were 44 cases reported worldwide, today the figure is closer to 50. Many authors suggest that this condition does go unrecognised, with most of the reported cases being in Europe and the US, which probably represents an increased recognition of the condition in these countries.
MoCo deficiency syndrome is linked with the enzymes sulphite oxidase, xanthine dehydrogenase and aldehyde oxidase.
Typically, individuals present in the newborn period or in early infancy with intractable seizures and feeding difficulties. This condition is usually fatal, with death occurring by three years of age. However, some children do survive having severe developmental delay and neurological abnormalities.
This is the case for the sibling of the child reported in this study, whereas the patient herself was only found on biochemical analysis and cranial MRI, as the only reported problems were poor attention span and distractibility.2
She had, however, been noted to have dislocated lenses by her community optometrist. The reason for the characteristic dislocation of the crystalline lens is due to the alternative metabolic pathways that occur in this condition. Metabolites are substituted in connective tissue, which weaken the zonule of the lens.

Case report
Female patient aged 11
November 2000
The patient first presented with a history of visual difficulties at three to four years old. She was examined previously at an ophthalmology department and prescribed spectacles said to be:

R -18.50/+16.75x120; L -16.25/+15.50x65

The patient was not wearing spectacles. Unaided visions were found surprisingly to be 6/36 right and left. Ocular examination found bilateral subluxation of lenses up and out, with both lenses being clear and a few zonular fibres visible without dilation. The rest of the anterior segment examination was unremarkable as was the dilated fundus examination. Intraocular pressure was 12mmHg right and left.
Previously, the patient had tried soft contact lenses but encountered handling problems as she was too young. Retinoscopy was impossible through the phakic portion of the pupil so it was decided to correct the patient through the aphakic portion.

Refractive results were as follows:

R +18.50/-1.50 x 157.5 6/9, N6
L +19.50/-1.25 x 2.5 6/6+, N5

Spectacles were prescribed and dispensed.

March to December 2001
The patient was not wearing spectacles despite improved vision. At this point it was decided that contact lens fitting was an acceptable option.

Keratometry revealed:

R 8.50 along 5 L 8.40 along 175
8.15 along 95 8.00 along 5

There were no obvious contraindications to contact lens wear. Toric soft contact lenses were ordered from Contact Lens Precision Laboratories.

Specification:

R 9.10 14.30 +22.50/-2.00 x 148
L 9.00 14.30 +24.00/-1.50 x 15 GM3

Contact lens fit was found to be acceptable but visual acuities were only right 6/30 and left 6/40. At this point it was decided that spherical diagnostic lenses would be a sensible option in the fitting of this patient given the unexpected visual acuities and over-refraction results.

Final contact lens prescription was:

R 9.10 14.30 +19.50 6/6
L 9.00 14.30 +19.25 6/6

The lack of requirement for a cylindrical correction was put down to the centre thickness of the lens design and the material having a very low dehydration factor, thus giving a relatively 'rigid' soft lens that masked the corneal cylinder.
The lenses were considered to be acceptable to try, but it was felt that they would need to be modified as time went on. Further fitting was hampered by keratoconjunctivitis and excessive loss of lenses so it was not until the end of the year that the lenses were seen after any meaningful wearing time. At this point it was also suggested that a consultation regarding the possibility of lensectomies and intraocular implants should be obtained. The consultant ophthalmic surgeon who undertook this was unhappy to proceed in this case, so the patient was referred back for continued contact lens fitting.

January 2002 to date
Contact lens wear has been more successful during this period and the lenses have been modified to give improved fitting and stability to the visual acuity.
Also, material change has been made from GM3 to GM3 70 as both cornea showed early signs of hypoxia. The patient maintains a good level of acuity at right 6/9+ L 6/6 with no adverse corneal observations and a reasonable wearing time of eight hours a day.

Comments
The management of this case is not in itself any different than you would expect in any case of lens dislocation for whatever its cause, be it inherited or acquired.
When the lenticular dislocation is such that the border of the crystalline lens is causing considerable difficulty in prescribing a satisfactory spectacle prescription then the choice is to treat the patient as aphakic or refer for surgery, with the possibility of an intraocular implant.
What is interesting is the very rare underlying condition that led to this patient receiving HES treatment and in terms of contact lens practice, the soft lens material used masking the corneal astigmatism.
It is interesting to note that the patient's sibling who has profound neurological abnormalities has little by way of lens dislocation and only a minimal refractive error, so the degree of lens dislocation does not seem to relate to the severity of the MoCo deficiency syndrome.
What this patient shows is that, despite having the same phenotype as her sister, the condition which presented late at the age of six (indeed, it was late on even in her sister's case at one year of age) does have variable expression both in terms of neurological defects and in the severity of the ocular complications.

References
1 Kanski J. Clinical Ophthalmology Ð A Systematic Approach, 2nd edition. Oxford: Butterworth-Heinemann, 1989: 255-258.
2 Hughes E F, Fairbanks L et al. Molybdenum cofactor deficiency Ð phenotypic variability in a family with a late-onset variant. Developmental Medicine and Child Neurology, 1998; 40:57-61.

Steve Johns is principal optometrist at North Devon District Hospital