Stargardt's Dystrophy

Introduction

Most common childhood macular dystrophy, with a prevalence of 1/8000 to 1/10000.
- Usually of AR inheritance, but can be AD
- Onset is usually early childhood, but can also be in early adulthood, and rarely in late adulthood

Pathophysiology:
- Caused by a mutation in the ABCA4 gene that encodes ATP-binding cassette membrane proteins in the PR OS
- Overall 700 different mutations have been found on the ABCA4 gene.
- Important for active transportation across cellular membranes, such as amino acids, peptides, ions, lipids, fatty acids and esp. retinoid cycle
- The mutations leads to defective transport of retinoids such as A2E, which causes abnormal lipofuscin accumulation in the RPE

Dead Giveaways

Fundus Examination

A considerably big giveaway, however, will need to distinguish between multifocal pattern dystrophy simulating Stargardt's diseases
The very distinct yellow fleck. Note also the loss of the foveal reflex

FAF:

Shows pigment mottling, and mild pigmentary disturbance in the early stages
Shown below, the pigment mottling and atrophy can show a beaten metal appearance.

Shows the early pigment disturbances and the macular atrophy

There are 3 primary types of Stargardt's disease, which can be attributed to ffERGs

ERG:

This usually has 3 groups, depending on the type of Stargardt's disease
Generally the prognosis is group 1 > 2 > 3

Fundus Flavimaculatus

A similar appearance condition with similar phenotypes
Only difference is a later onset, slower visual deterioration, flecks are more diffuse and macular is less involved
May be associated with ABCA4
Fundus Flavimaculuatus

diagnostic features

The age of onset is variable, with earlier onset age being more common.

Age of onset determines clinical presentation, and rate of progression
Though a later onset typically indicates milder phenotype and a better overall prognosis

Additionally, residual ABCA4 activity is associated with severity of disease phenotypes

Early onset --> severe/moderate mutations
- Associated with early onset RPE and cone-rod dystrophies
Late onset --> mild mutations

Symptoms:

Reduced central vision function, as VA depends on foveal involvement
Central scotomas
Colour vision abnormalities
Photophobia
Slow dark adaptation

Clinical Signs:

Loss of foveal reflex and mild pigmentary disturbances + yellow flecks
In late stage disease, Bull's eye maculopathy can occur, or just macular atrophy in general
OCTs
- Shows the flecks as hyper-reflective zones on the apical RPE, and is very widespread
- Macular cystic space seen, as well as breaks in the RPE-Bruch's membrane complex. EZ, interdigitation zone, and ELM is disrupted. Herniation occurs in the retina and Bruch's membrane