Metabolic and Nutritional Disease Flashcards
What are the major nutrients needed for proper development and growth?
Macronutrients (fat, carbs, proteins) and micronutrients (vitamins, minerals, amino acids, fatty acids) and water.
Nutritional disorders
Occur when major nutrients are either unavailable or deficient or ingested in excess.
What are genetically determined errors of metabolism generally associated with?
Seldom occur. Specific enzyme deficiencies and result in blockage of amino acid, carb or lipid metabolism, with reduction of some substances and accumulation of others. Some can be lessened with therapy. You can screen at birth via testing amniotic fluid. NOTE: Usually autosomal recessive.
How do genetically determined errors of metabolism express clinically?
Range from specific focal abnormalities to mental retardation. There is variation in age of onset, rate of progression and organ and skeletal involvement.
What is phenylketonuria (PKU)?
Disorder of AA metabolism such that phenylalanine cannot breakdown to tyrosine. It is especially important that pregnant women observe a proper diet.
What are the biological effects of PKU?
Impairs brain development, increased urinary excretion of phenylpyruvic acid, hypomyelination, gliosis, microcephaly, and no lysosomal storage.
What are the clinical features of PKU?
Mental retardation, seizures, hyperactivity, decreased pigmentation of the hair and skin (due to lack of melanin w/I tyrosine).
What test can you use to test for PKU?
Guthrie test-serum analysis
What is galactosemia?
Carb disorder; deficiency of galactose-1-phosphate uridyl transferase leads to accumulation of galactose-1-phosphate and galactosuria and hypergalactosemia.
Where do the metabolite of galactose accumulate in galactosemia?
Liver, spleen, kidney, cerebral cortex, and lens of the eye.
What the the clinical features of galactosemia?
Jaudince, liver damage (fatty chagne, widespread scarring, hepatomegaly), cataracts, neural damage (nerve cell loss, gliosis, edema), aminoaciduria due to accumulation in the liver.
What are the long-term complications of galactosemia?
Cataracts, speech and neurological deficits and mental retardation in older children.
How do you typically diagnose galactosemia?
Array of transferase in W/RBCs; antenatal via enzyme assays or DNA analysis.
What is lysosomal storage disease?
Lack of proper enzymes in lysozomes. Thus, catabolism remains incomplete leading to accumulation within lysosomes. These are rare!
How does LSD (lysosomal storage disease) present clinically?
Progressive mental and motor deterioration and death is the usual pattern.
What is Tay-Sachs disease (GM2 gangliosidis)?
Accumulation of gangliosides within the brain as a result of the catabolic enzyme defect (deficiency in the a subunit of hexoaminidase A) necessary for the degradation of GM2). GM2 is stored within neurons, axon cylinders of nerves, glial cells throughout CNS.
How does Tay-Sachs manifest?
Affected cells appear swollen or “foamy” with lipid vacuolation. Infants appear normal at birth but motor weakness begins to develop at 3-6 months of age, followed by mental retardation, blindness, and severe neurological dysfunction. Death occurs within 2-3 years.
What population is Tay-Sachs most common?
Among Ashkenazi Jews (1/30)
What is Niemann-Pick disease?
Primary deficiency of acid sphingomyelinase and thus sphingomyelin. Two types (A/B).
What happens in Type A Niemann-Pick disease?
Breakdown of sphingomyelin into ceramide and phosphorylcholine is impaired and excess sphingomyelin accumulates in phagocytic cells and neurons.
Which organs are most affected in Type A Niemann-Pick disease?
Spleen, liver, bone marrow, lymph nodes, lungs; affected neurons are enlarged and vacuolated as a result of the storage of lipids
How does Type A Niemann-Pick disease manifest itself?
Massive visceromegaly and severe neurological deterioration. Death usually occurs within the first 3 years of life.
How do Type B Niemann-Pick patients manifest?
Orangomegaly but no neurological symptoms.
How can you diagnose Type B Niemann-Pick disease?
Sphingomyelinase activity in leukocytes or cultured fibroblasts can be used for diagnosis of suspected cases as well as carriers.
What are some autosomal dominant metabolic disorders?
Familiar hypercholesterolemia (impaired transport of LDL into cells) and acute intermittent porphyria (impaired heme synthesis and the accumulation of the intermediate porphyrin).
How does acute intermittent porphyria manifest?
It usually doesn’t; low levels of the missing enzyme porphobilinogen deaminase (PGBD) are generally not sufficient; BUT hormones/drugs/diet can afffect this.
What are some examples of X-linked recessive metabolic disorders?
Diabetes insipidus and Lesch Nyhan syndrome.
What is the pathology behind Lesch Nyhan syndrome (LNS)?
Lack of enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) causes a build-up of uric acid in all body fluids and leads to several symptoms.
What are the symptoms Lesch Nyhan syndrome (LNS)?
Severe gout, poor muscle control, moderate retardation all in the first year of life. In the 2nd year, you get self-mutilation (finger/lip biting). You can also have abnormally high levels of uric acid levels, which cause sodium urate crystals to form in the joints, kidneys, CNS, and other tissues; neurological symptoms include facial grimacing, involuntary writhing, and repetitive movements of the arms and legs.
A lack of HPRT can cause the body to poorly utilize vitamin B12, so what results?
Megaloblastic anemia.
What kinds of acquired disorders are most common, and give me an example.
Hypoxia-associated disorders. Atherosclerosis results and usually stays silent until it progresses.
What is the earliest pathological sign of atherosclorosis?
Fatty streak, which develops into fibro-fatty plaque, which narrows the vessel lumen.
