Hereditary congenital-periodic fever, marfan. Flashcards
a. Disorders of connective tissue: Marfan’s syndrome, osteogenesis imperfecta, Ehlers-Danlos syndromes, pseudoxanthoma elasticum, hypermobility syndrome, others b. Mucopolysaccharidoses c. Osteochondrodysplasias: multiple epiphyseal dysplasia, spondylepiphyseal dysplasia d. Inborn errors of metabolism affecting connective tissue: homocystinuria, ochronosis e. Storage disorders: Gaucher’s disease, Fabry’s disease, Farber’s lipogranulomatosis f. Immunodeficiency: IgA deficiency, complement co
What illnesses comprise the periodic fever syndromes?
Periodic fever syndromes include
1) tumor necrosis factor receptor associated periodic syndrome (TRAPS)
2) NLRP 12-Associated Periodic Syndrome (NAPS)
3) Familial Mediterranean Fever (FMF),
4) Hyper IgD Syndrome (HIDS),
5)Cryopyrin-associated periodic syndrome (CAPS).
FMF attacks last 3 days and HIDS attacks last six days.
What does Pyrin do?
Pyrin is made of 781 amino acids with a B box zinc finger domain and a DAPIN domain resulting in affinity for cytoskeletal elements. It probably functions to suppress activation of caspase 1 and thus production of interleukin one beta.
I’ll is hyperimmunoglobulin D syndrome (HIDS) related to mevalonic aciduria?
Hyperimmunoglobulin D syndrome is related to genetic defects in the mevalonic kinase gene (MVK) wherein severe defects result in mevalonic aciduria and partial defects affecting enzymatic action result in hyperimmunoglobulin D syndrome. Deleting a single MVK allele In mice results in hyperimmunoglobulin D. Mevalonic aciduria occurs during febrile episodes whereas IgD concentration does not vary. IL-6, TNF alpha, IL-1 RA, soluble TNF receptor are also increased during attacks but not IL-1 alpha, beta, or IL-10.
IgD from patients with HIDS may increase IL-1 and IL-6 from normal mononuclear cells, and also increases responsiveness to lipopolysaccharide.
What are the features of down syndrome?
Dysmorphic features of down syndrome include:
flat facial profile/nasal bridge
molded or dysplastic years,
low set small ears,
protruding tongue,
short neck,
excessive skin at native of neck,
narrow pallet, abnormal teeth,
short broad hands,
incurved fifth finger with hypoplastic mid-phalanx,
transverse palmar crease,
space between first and second toes,
hyperflexibility of joints.
How do defects in Methalenetetrahydrofolate reductase (MTHFR) result in excessive homocysteine?
MTHFR provides the free methyl group so that homocysteine can return to methionine.
The 677 CT mutation (CC wild type) results in partial deficiency with modest increases in homocysteine, other more severe mutations markedly increase the homocysteine level.
What are the basis of congenital immunodeficiency syndromes, and how many have been described?
There are over 250 described immunological deficiency syndromes of which 50 are due to dominant negative mutations. Those with mendelian inheritance are dominant negative by virtue of haploinsufficiency. Those with incomplete penetrance may also be due to haploinsufficiency combined with somatic mutation in the normal gene. CTLA-4 deficiency has such a pattern.
One then the inheritance is usually polygenetic.
