color blindness

Neuraminidase Deficiency

Clinical Characteristics
Ocular Features: 

A cherry red spot is may be seen in late childhood or early adolescence.  It occurs in nearly 100% of patients with type I while only 75% of type II patients have this feature possibly because their early death from the more severe systemic disease prevents full ascertainment.  Visual acuity is reduced, sometimes severely.  Some but not all individuals have corneal and lens opacities.  A subtle corneal haze has also been seen.  Nystagmus has been reported. 

Systemic Features: 

This is a neurodegenerative disorder with progressive deterioration of muscle and central nervous system functions.  Myoclonus, mental deterioration, hepatosplenomegaly, muscle weakness and atrophy are common.  The defect in neuraminidase activity leads to abnormal amounts of sialyl-oligosaccharides in the urine.  Spinal deformities such as kyphosis are common.  Deep tendon reflexes are exaggerated.  Ataxia and hearing loss may be present.  Coarse facies, a barrel chest, and short stature are characteristic.  Hepatic cells contain numerous vacuoles and numerous inclusions.

Sialidosis types I and II are both caused by mutations in the neuroaminidase gene.  Type I is associated with milder disease than type II which has an earlier age of onset and may present in infancy or even begin in utero.  Early death within two years of age is common in the congenital or infantile forms.  There is, however, significant variability in age of onset and the course of disease among types. 

Genetics

The sialidoses are autosomal recessive lysosomal storage disorders resulting from mutations in the NEU1 gene (6p21.3) which lead to an intracellular accumulation of glycoproteins containing sialic acid residues.  Both types I and II are caused by mutations in the same gene. 

Treatment
Treatment Options: 

Treatment is focused on symptom management. 

References
Article Title: 

Color Blindness, Red-Green, Partial

Clinical Characteristics
Ocular Features: 

Human color vision is trichromatic and requires the normal function of three classes of cones responding to wavelengths of approximately 420nm (blue cones), 530 nm (green cones), and 560 nm (red cones).  Dichromatic color vision discussed here is based on responses of red and green cones whose pigments are generated from contiguous gene regions on the X chromosome encoding OPN1MW (green pigment), and OPN1LW (red pigment).

The degree of color deficiency is variable and some males are so mildly affected that they are unaware of any defect until tested.  The human eye is capable of seeing about a million colors which is made possible in part by the wide range of comparative signal outputs from the three classes of cones.  In addition, the ratio of red and green cones varies among individuals and these factors collectively influence how each individual interprets the spectrum of wavelengths that enter the eye.  The phenotype of red-green color blindness is highly variable.  

Four subclasses of red-green color vision defects are recognized:

               Protanopia - only blue and green cones are functional (1 percent of Caucasian males) 

               Deuteranopia - only blue and red cones are functional (1 percent of Caucasian males)

               Protanomaly - blue and some green cones are normal plus some anomalous green-like cones (1  percent of Caucasian males)

               Deuteranomaly - normal blue and some red cones are normal plus some anomalous red-like cones (5 percent of Caucasian males)

Blue color blindness (tritanopia; 190900) is the result of mutations in the OPN1SW gene on chromosome 7. ERG flicker responses can be used to define the type and nature of the cone defects. 

Systemic Features: 

There are no systemic abnormalities. 

Genetics

Red-green color perception is based on gene products called opsins which, combined with their chromophores, respond to photons of specific wavelengths.  The OPN1LW and OPN1MW genes reside in a cluster with a head-to-tail configuration on the X chromosome at Xq28.  Red-green color vision defects are therefore inherited in an X-linked recessive pattern.  There is a single gene for the red cone opsin but there are multiple ones for the green pigment.  Only the red gene and the immediately adjacent green pigment gene are expressed.  All are under the control of a master switch called the locus control region, LCR.

These DNA segments undergo relatively frequent unequal crossovers which can disrupt the color sensitivity of the gene products so that red-green colorblindness in some form is the most common type of anomalous color vision.  It is found in approximately 8% of males and perhaps 0.5% of females. 

Pedigree: 
X-linked recessive, carrier mother
X-linked recessive, father affected
Treatment
Treatment Options: 

No treatment is available for red-green color blindness although appropriately tinted lenses may enhance the perception of certain shades for specific tasks. 

Early work in non-human primates suggest that viral-mediated gene therapy can restore trichromacy to at least some extent.

References
Article Title: 

Colorblindness-Achromatopsia 2

Clinical Characteristics
Ocular Features: 

Patients with this congenital, nonprogressive condition often have nystagmus as infants which may improve later. Eccentric fixation secondary to a small central scotoma is often present.  Visual acuity is 20/200 or worse.  Hyperopia is common.  Photophobia is extreme and vision under daylight conditions improves in dim light.  Patients are unable to distinguish any colors.  However, there is considerable variability in symptoms and some individuals retain some color perception and have better visual acuity (sometimes 20/80) than others suggesting some residual cone function.  The term ‘incomplete achromatopsia’ is sometimes applied to such cases but the molecular basis for this variation is unknown.  Optical coherence tomography reveals the central retina to be thinner than in normal controls.  The fundus appearance is normal, however.

ERG responses indicate an absence of cone function with no photopic responses. 

Systemic Features: 

There are no associated systemic abnormalities. 

Genetics

Mutations in CNGA3 account for approximately 25% of cases of achromatopsia.  ACHM2 is an autosomal recessive disorder caused by mutations in CNGA3 (2q11).  Mutations in this gene also have been found in rare patients with progressive cone dystrophies.  A clinically similar but genetically distinct disorder, ACHM3, results from mutations in CNGB3 (262300).  Mutations in GNAT2 (ACHM4; 139340) and PDE6C (ACHM5; 613093) also cause achromatopsia. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

There is no treatment for the underlying condition but darkly tinted lenses can help in bright light.  Red contact lenses can alleviate photophobia and improve vision as well.  Low vision aids and vocational training can be of great benefit.  In spite of the poor vision, some patients may find that correction of the hyperopia enables them to see better. 

References
Article Title: 

Colorblindness-Achromatopsia 3

Clinical Characteristics
Ocular Features: 

Achromatopsia 3 is a congenital, nonprogressive form of blindness.  It is sometimes referred to as a rod monochromacy or stationary cone dystrophy.  Symptoms are usually present at birth or shortly thereafter.  Patients have pendular nystagmus, progressive lens opacities, severe photophobia, 'day' blindness, and, of course, color blindness.  High myopia is a feature in some populations.  Vision in daylight is often 20/200 or less but vision in dim light is somewhat better. The central scotoma often leads to eccentric fixation. 

The ERG shows a complete absence of cone function.  Optical coherence tomography has demonstrated a reduction in macular volume and thickness of the central retina, most marked in the foveolar region, presumably due in some way to the absence or dysfunction of cone photoreceptors.  Few histologic studies of adequately preserved retina have been reported but those available suggest dysmorphism of cones in the central macula.  The clinical appearance of the retina is usually normal. 

Systemic Features: 

There are no associated systemic abnormalities. 

Genetics

This is an autosomal recessive form of color blindness caused by mutations in CNGB3 (8q21-q22).  This mutation is found in nearly half of patients with achromatopsia.  It is especially common among Pingelapese islanders of the Pacific Caroline Islands where consanguinity occurs frequently due to the founder effect resulting from a 1775 typhoon.  A progressive cone dystrophy has been found in a few patients with mutations in this gene.

Other achromatopsia mutations are in CNGA3 causing ACHM2 (216900), GNAT2 causing ACHM4 (139340), and PDE6C causing ACHM5 (613093).   

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available but darkly tinted lenses can alleviate much of the photophobia.  Low vision aids and vocational training should be offered.  Refractive errors should, of course, be corrected and periodic examinations are especially important in children. 

References
Article Title: 

The cone dysfunction syndromes

Michaelides M, Hunt DM, Moore AT. The cone dysfunction syndromes. Br J Ophthalmol. 2004 Feb;88(2):291-7. Review.

PubMed ID: 
14736794
Subscribe to RSS - color blindness