39 terms

MCB II Block III Diseases

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GSD VII Tarui
Mutation in PFK in muscle leads to build up of Glucose-6-P which inhibits glycogen phosphorylase which leads to inability of the muscle to break down glycogen
GSD II Pompe
Mutation in lysosomal α(1→4) glucosidase leads to build up of structurally aberrant glycogen particles which causes muscle weakness, massive cardiomegaly and infantile heart failure
GSD III Cori
Mutation in debranching enzyme leads to fasting hypoglycemia and abnormal glycogen structure
GSD IV Andersen
Mutation in branching enzyme leads to long, needle-like α(1→4) causing damage to cells which causes hypotonia, developmental retardation and atrophy
GSD V McArdle
Mutation in skeletal muscle glycogen phosphorylase deficiency causes temporary weakness and cramping after excercise, no rise in blood lactate during strenuous exercise, myoglobinuria
GSD VI Hers
Mutation in liver glycogen phosphorylase leads to mild fasting hypoglycemia
GSD I von Gierke
Mutation in glucose-6-phosphatase (a) or translocase (G6PT1) (b) (liver and kidney) leads to increased PPP, glycolysis (lactate) and fatty acid synthesis which causes fatty liver and renomegaly, progressive renal disease, growth retardation and delayed puberty, lactic acidemia, hyperlipidemia and hyperuricemia
GSD 0
Mutation in glycogen synthase leads to inability to produce glycogen which causes lethargy, nausea, seizures, pallor and vomiting; treatable by frequent protein rich meals (gluconeogenesis) and nightly slow release glucose preparation
Refsum Disease
Mutation in phytanoyl-CoA hydroxylase leads inability to degrade phytanic acid and its accumulation which causes peripheral polyneuropathy, cerebellar ataxia, retinitis pigmentosa and icthyosis
X-linked adrenoleukodistrophy
X-linked mutation in the ABCD1 (ATP Binding Cassette) leads to inability to import VLCFAs into peroxisomes and their accumulation in brain glial cells and adrenal cortex which causes myelin breakdown and adrenal atrophy linked with apathy, behavioral changes, spasticity, ataxia, visual loss and death a few years later
Zellweger Syndrome
Autosomal recessive mutation in peroxin leads to inability to import peroxosomal enzymes into peroxisomes which causes VLCFA accumulation in glial cell membrane and liver leading to abnormal brain development and defects in myelination (seizures, mental retardation), hepatomegaly and liver failure
GM1 Gangliosidosis
Mutation in β-galactosidase leads to accumulation of gangliosides (GM1) and keratan sulfate which causes neurologic deterioration, hepatosplenomegaly, skeletal deformities and cherry red macula in infantile form
Tay-Sachs disease
Mutation in α subunit of β-hexosaminidase A leads to accumulation of gangliosides (GM2) which causes rapid, progressive and fatal neurodegeneration, blindness, seizures, excessive startle response, muscle weakness, cherry-red macula
Sandhoff disease
Mutation in β subunit of β-hexosaminidase A and B leads to accumulation of GM2 and globosides which causes similar symptoms as Tay-Sachs, but also visceral involvement
Fabry Disease
X-linked inherited mutation in α galactosidase leads to accumulation of globosides which causes red-purple skin rash, kidney and heart failure, burning pain in lower extremities
Gaucher Disease
Mutation in β-glucosidase leads to accumulation of glucocerebrosides which causes hepatosplenomegaly, osteoporosis of long bones and CNS involvement in rare infantile and juvenile forms
Metachromatic Leukodystrohy
Mutation in arylsulfatase A leads to accumulation of sulfatides which causes cognitive deterioration, demyelination, progressive paralysis and dementia in infantile form, nerves stain yellow-brown and cresyl violet
Niemann-Pick disease (A and B)
Mutation in sphingomyelinase leads to accumulation of sphingomyelin which causes hepatosplenomegaly, neurodegenerative course (A) and cherry-red macula (A)
Farber disease
Mutation in ceramidase leads to accumulation of ceramide which causes painful and progressive joint deformity, subcutaneous nodules of lipid-laden cells, hoarse cry, tissue granulomas and cherry red macula
Krabbe Disease
Mutation in β-galactosidase leads to accumulation of galactocerebrosides which causes mental and motor deterioration, blindness and deafness, near total loss of myselin and globoid bodies in white matter of brain
Niemann Pick Disease (C)
Mutation in NPC1/2 causes inability in movement of cholesterol within cells which causes ataxia, inability to move the eyes vertically, poor muscle tone, severe liver disease and interstitial lung disease
Smith-Lemli-Opitz syndrome
Mutation in 7-dehydrocholesterol reductase deficiency results in lack of cholesterol synthesis and lack of action of Shh during emryo CNS and limb development(as it needs to be modified by cholesterol) which leads to distinctive facial features, microcephaly, mental retardation, learning disabilities and behavioral problems
Deficiency of 5α-reductase
Mutation in 5α-reductase results in lack of production of dihydrotestosterone which causes external appearance at birth predominantly female of a genetic male followed by an increase in secondary male sexual characteristics at puberty
Addisons disease
Autoimmune/Tuberculosis destruction of the adrenal cortex leads to lower levels of cortisol and aldosterone secretion leads to steadily worsening fatigue, loss of appetite and some weight loss, and low blood pressure
Cushing syndrome
Elevated levels of cortisol due to pituitary tumour causes high blood pressure, diabetes and obesity
3-β-hydroxysteroid dehydrogenase deficiency
Mutation in 3-β-hydroxysteroid dehydrogenase results in virtually no glucocorticoids, mineralcorticoids and active androgens and estrogens which causes large amount of sodium secretion in urine and abnormal sexual development
17-α-hydroxylase
Mutation in 17-α-hydroxylase results in virtually no sex hormones or cortisol produced and increased production of mineralcorticoids which causes hypertension (increased sodium and fluid retention), hypokalemia and abnormal sexual development
21-α-hydroxylase deficiency
Mutation in 21-α-hydroxylase results in virtually no mineral and glucocorticoids production and overproduction of sex hormones which causes large amount of sodium secretion in urine and masculization of external genitalia in females and early virilization in males
11-β1-hydroxylase deficiency
Mutation in 11-β1-hydroxylase leads to lower serum levels of cortisol, aldosterone and corticosterone, but increased production of deoxycortisol which causes fluid retention (by blocking the renin/angiotensin system) and masculization of external genitalia in females and early virilization in males
Tangier Disease
Mutation in ABCA1 transporter results in inability to transport cholesterol from tissue cells into HDLs and HDL deficiency which causes increased risk of atherosclerosis
Type I hyperlipoproteinemia
Mutation in lipoprotein lipase or apoCII deficiency leads to presence of chylomicrons in fasting blood which causes opalescent retinal blood vessels, eruptive xanthoma, hepatosplenomegaly and hepatic steatosis
Apo CIII gain of function
Gain of function mutation in ApoCIII leads to inhibition of lipoprotein lipase and high triacylglyceride blood lelvels which causes cardiovascular problems, inflammation and insulin resistance (which in turn exacerbates the problem, because high blood glucose increases Apo CIII expression)
Type IIA hyperlipoproteinemia
Mutation in LDL receptor leads to inability to uptake LDLs and IDLs which causes cutaneous xanthoma, xanthelasmas, corneal arcus, tendonous xanthomas and premature atherosclerosis in aortic root
Type IIB hyperlipoproteinemia
Decreased LDL receptor and increased ApoB protein results in higher circulating LDL and VLDLs which causes visceral obesity, glucose intolerance, diabetes, insulin resistance, hypertension, hyperuricemia and increased risk of premature cardiovascular disease
Type III hyperlipoproteinemia
Polymorphism of ApoE (heterozygous or homozygous ApoE2) results in raised IDL and chylomicron remnants which leads to severe coronary heart disease and xanthomas
Type IV Hyperlipoproteinemia
Increased production or impaired metabolism of VLDL leads to eruptive xanthoma if TAGs are very high, coronary and peripheral atherosclerosis
Type V hyperlipoproteinemia
GPIHBP1 and ApoA5 mutations or high carb diet in type I leads to high VLDL and chylomicrons in fasting plasma which causes recurrent pancreatitis, eruptive xanthomas and lipaemia retinalis
Abetalipoproteinemia
Mutations in the MTP leads to lack of transfer of lipids to nascent chylomicrons and VLDL in intestine and liver which causes steatorrhea, diarrhear, failure to thrive, pigmented retinopathy with decreased night and colour vision, cerebellar ataxia, acanthocytosis
LCAT deficiency
Mutation in LCAT leads to lack of normal cholesterol esterification and impairement of mature HDL formation and rapid catabolism of circulating apoA1 which causes progressive corneal opacification due to deposition of free cholesterol in the lens