Systemic & syndromes Flashcards
what is CDG?
congenital disorder of glycosylation
what are the findings of CDG
- inherited condition
- affects many parts of the body.
- vary widely among affected individuals, sometimes even among members of the same family.
- develop signs and symptoms during infancy.
- may have weak
- muscle tone (hypotonia),
- retracted (inverted) nipples,
- an abnormal distribution of fat, e
- (strabismus),
- developmental delay,
- (failure to thrive).
- Infants with PMM2-CDG also frequently have an underdeveloped cerebellum,
- Distinctive facial features are
- high forehead,
- a triangular face,
- large ears, and a
- thin upper lip.
- elevated liver function test results,
- seizures,
- About 20 percent of affected infants do not survive the first year of life due to multiple organ failure.
- TAffected individuals may also experience stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis.
- During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (kyphoscoliosis), impaired muscle coordination (ataxia), and joint deformities (contractures).
- Some have retinitis pigmentosa
- Females with PMM2-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, females with PMM2-CDG do not go through puberty.
prevalence of CDG
More than 800 individuals with PMM2-CDG have been identified worldwide.
what happens in CDG?
This gene provides instructions for making an enzyme called phosphomannomutase 2 (PMM2). The PMM2 enzyme is involved in a process called glycosylation, which attaches groups of sugar molecules (oligosaccharides) to proteins. Glycosylation modifies proteins so they can perform a wider variety of functions. Mutations in thePMM2 gene lead to the production of an abnormal PMM2 enzyme with reduced activity. Without a properly functioning PMM2 enzyme, glycosylation cannot proceed normally. As a result, incorrect oligosaccharides are produced and attached to proteins. The wide variety of signs and symptoms in PMM2-CDG are likely due to the production of abnormally glycosylated proteins in many organs and tissues.
what is kearns-sayre syndrome?
- genetic condition that affects many parts of the body BUT SPECIALLY THE EYES
- young people before 20 yo
- progressive external ophthalmoplegia
- ptosis
- pigmentary retinopathy degeneration
- cardiac blocks
- ataxia
- increased CSF proteins
- muscle weakness
- deafness
- kidney problemsThe muscles have an excess of mitochondria
- 1 in 100K individuals
- mitochondrial inheritance
what is a CLIA lab?
Clinical Laboratory Improvement Amendments (CLIA) regulate laboratory testing and require clinical laboratories to be certificated by their state as well as the Center for Medicare and Medicaid Services (CMS) before they can accept human samples for diagnostic testing
what is LCA triad?
- decreased vision
- nystagmus
- flat ERG
- Paradoxical pupillary response (pupils do not constrict, or dilated and then constrict slowly)
others are oculo-digital reflex, pigmentary retinopathy, strabismus
LCA frequency
2-3 per 100,000
- How many LCA genes have been identified?
- which are the 3 most common genes?
- what percentage represent the rest of the genes?
- in what percentage of LCA patients the genes remains unknown?
- 14 genes
- RPE65, CEP290, CRB1, GUCY2D, CRX
- small %
- 30%
features of CRX mutation in LCA
The CRX gene provides instructions for making a protein called the cone-rod homeobox protein.
This protein is called a transcription factor.
In the retina, the cone-rod homeobox protein is necessary for the normal development of light-detecting cells called photoreceptors.
RPE65 functions? where is it produced?
The RPE65 protein is involved in a multi-step process called the visual cycle,
When light hits photosensitive pigments in the retina, it changes 11-cis retinal (a form of vitamin A) to
all-trans retinal.
The RPE65 protein then helps convert all-trans retinal back to 11-cis retinal so the visual cycle can begin again.
its produced on the RPE.
what happens in the visual cycle?
When light hits photosensitive pigments in the retina, it changes 11-cis retinal (a form of vitamin A) to
all-trans retinal.
The RPE65 protein then helps convert all-trans retinal back to 11-cis retinal so the visual cycle can begin again.
what is curcumin?
The plant turmeric (Curcuma longa) is very well known in India.
Traditionally, turmeric was used for nearly every health condition known - from smallpox to a sprained ankle.
This plant has a compund known as curcumin. Just as oranges are a source of vitamin C, turmeric is a source of curcumin. Today, we extract curcumin from turmeric to use as a natural medicine
what is cockayne syndrome?
RARE syndrome
- microcephaly
- failure to thrive
- delayed development
- photosensitivity
- skin light sensitivity
- hearing loss
- vision loss
- tooth decay
- bone abnormalities
- brain abnormalities
- cold hands and feet
*
cockayne syndrome frequency?
2-3 per million