Rare GI Diseases Flashcards
How would a deficiency of MCAD affect energy metabolism
Reduced beta-oxidation will increase cellular demand for glucose leading to severe hypoglycemia
Also, despite the decreased rate of beta oxidation, the cells will not be able to produce ketone bodies b/c Acetyl CoA is reduced
Levels of what biomacromolecule would you expect to be elevated in Zellweger Syndrome?
VLCFAs due to absence of peroxisomes
what are unique clinical manifestations of Zellweger Syndrome?
Helen Keller deficits
What is the pathogenesis of Refsum’s disease?
defect of the enzymes involved in alpha-oxidation of branched FACs
what are the clinical manifestations of Refsum’s disease?
ataxia; neuropathy; retinitis pigmentosa
What is the pathogenesis of Niemann-Pick Disease Type A & B
Insufficient activity of the sphingomyelinase; Type B has a better prognosis than type A
what are the clinical manifestations of NP disease Type A?
Hepatosplenomegaly; V/D, delayed developmental milestones, Interstitial lung disease, progressive loss of motor skills, hypotonia
Advanced State: macular cherry-red spots in retina
Main cause of death: respiratory failure
what are the clinical manifestations of NP disease Type B?
Interstitial lung disease; hepatosplenomegaly; thrombocytopenia; hyperlipidemia; foamy storage histiocytes
NO NEUROLOGICAL SYMPTOMS
Composite a list of disease assoc. w/ degradation defects of glycosphingolipids
Tay-Sachs Disease
Fabry Disease
Gaucher Disease
Gangliosidosis
sandhoff disease
Niemann-Pick Disease
Metachromatic leukodystrophy
List the clinical manifestations of Tay-Sachs disease?
rapid neurodegeneration, cherry-red macula in eyes, seizures, muscular weakness, blindness
What are the clinical manifestations of Fabry Disease
red-purple skin rashes; kidney & heart failure; neuropathic pain in hands & feet; later stage: angiokeratomas
More common in young boys due to X-linked recessive inheritance pattern
What is the pathogenesis of demyelination seen in pts. w/ metachromatic leukodystrophy
reduced arylsulfatase activity results in accumulation of cerebroside sulfate in CNS & PNS
What are the clinical manifestations of metachromatic leukodystrophy
progressive paralysis & dementia
what are the clinical manifestations of Gaucher disease
Hepatosplenomegaly; osteoporosis of long bones
Sandhoff Disease presents w/ all the neurological symptoms of Tay-Sachs Disease + what addition symptoms
visceral involvement
what is the pathogenesis of demyelination assoc. w/ Krabbe Disease
defective lysosomal galactocerebrosidase; accumulation of globoid bodies of galactolipids and lipid-laden macrophages results in demyelination
List the clinical manifestations of Krabbe disease?
microcephaly; blindness due to optic atrophy; deafness; absent reflexes
Adenocarcinoma is an inevitability for pts. w/ Familial Adenomatous polyposis; When do pts. start to develop complications
2nd decade of life
What osseous abnormalities can be seen w/ FAP-variant Gardner Syndrome
osteomas in the skull & mandible; odontomas; extra teeth;
what cutaneous feature can be observed on a pt. w/ FAP-variant Gardner syndrome
epidermoid & sebaceous cysts; lipomas; fibromas; fibromatosis or desmoid tumors
What keratopathy can also be seen w/ FAP
congenital hypertrophy of the retinal pigment epithelium
Compare/Contrast FAP vs. AFAP (attenuated FAP)
AFAP: polyps < 100; primarily only affects the proximal colon; later onset of CRC
What additional clinical manifestations are found in pts. w/ FAP Variant Turcot Syndrome
medulloblastoma; anaplastic astrocytoma; ependymoma; glioblastoma multiforme
Compare/Contrast the different mutations involved in the pathogenesis of FAP & lynch syndrome
FAP: APC gene
LS: DNA mismatch repair of MLH & MSH genes; microsatellite instability
pts. w/ lynch syndrome are at an increased risk of developing what additional extracolonic malignancies
uterus, ovarian, & biliary system
What LS variant is assoc. w/ sebaceous neoplasms
Muir-Torre syndrome
List the clinical manifestations of Peutz-Jeghers syndrome
multiple hamartomas scattered throughout the GI canal; melanin deposits in lips, gums, face, genitals, & hands/feet
pts. w/ PJ syndrome are at increased risk for what malignancies
pancreatic, stomach, breast
what gene mutation is assoc. w/ serrated adenomatous polyposis
BRAF
what is the pathogenesis of type 1 Von Gierke disease
deficiency of glucose6phosphatase
Describe the pathogenesis of I-Cell disease
AKA mucolipidosis II;
deficiency of GlcNAc-1-phosphotransferase: involved in the posttranslational modification of lysosomal target sequences for multiple different lysosome enzymes
what are the clincal manifestations of mucolipidosis II
congenital dislocation of multiple joints such as kyphosis & club feet; umbilical and inguninal hernias;
hyperplastic gums; valvulopathies
what is the pathogenesis of Danon disease
deficiency of LAMP2
list the clinical manifestations of Danon disease
myopathy
cardiomyopathy
Mental Impairment
Impaired metabolism of methylmalonic acid leads to what physiological consequence
metabolic acidosis
What are the different pathogenesises of homocystinuria
Enzyme defects of cystine metabolism
defect in Vit. B12 metabolism
Vit B6 deficiency (cofactor for the cystathionine beta-synthase)
List the clinical manifestations of homecystinuria
osteoporosis; myocardial infarction; dislocation of the lenes
intellectual disability
what is the pathogenesis of Tyrosinemia Type 1
defect of the fumaryl-acetoacetate hydrolase
what are the clinical manifestations of Tyrosinemia Type 1
cabbage like odor of urine
liver failure
renal tubular acidosis
what is the pathogenesis of Hartnup disease?
defective transport system for aromatic AAs
what physiological consequence can result from hartnup disease
Vit. B3 deficiency; niacin produced from W
what is the pathogenesis of cystinuria?
defective transport of basic AAs & cystine; excess cystine can form kidney stones
what is the pathogenesis of MSUD?
deficiency of BCAA ketoacid dehydrogenase
how is MSUD managed
mega doses of Vit B.
What enzymes are deficient in atypical & classical PKU?
Atypical: dihydropteridine reductase (incredibly rare)
classical: phenylalanine hydroxylase
what is a clinical hallmark of PKU
musty urine odor due to unusual metabolites in the urine
What enzyme is defective in Alkaptonuria?
homogentisate oxidase
what is a clinical hallmark of Alkaptonuria?
Black urine upon exposure to light; pt.s also present w/ arthritis of the spine & abnormally dark pigmentation of cartilage & collagenous tissues
a deficiency of CPSI will lead to accumulation of what?
ammonium
deficiency of OTC will lead to the accumulation of what
a deficiency of this step in the urea cycle will cause accumulation of carbamoyl phosphate & depletion of ornithine
what are the clinical manifestations of CPSI & OTCase deficiencies
shortly after birth infants develop lethargy, irritability, vomiting, & coma
how does oral arginine help alleviate harmful symptoms assoc. w/ argininosuccinate lyase deficiency
depletion of arginosuccinate lyase will result in impaired cellular ability to convert argininosuccinate back to arginine: an essential step required for arginase conversation to ornithine
Therefore, a deficiency of this step can be bypassed via administration of supplemental arginine
An infant less than 24 hr. old, it admitted to the neonatal ICU for unstable vital signs shortly after birth; a urine analysis revealed an absence of orotic acid. What is the most likely diagnosis?
CPSI deficiency
