5 Written Questions

1. lysosome storage disease, accumulation of sphingolipids
2. fructose metabolism disorder, caused by a defect in the gene encoding Aldolase B in the major pathway of fructose metabolism, autosomal dominant, ~ 1:20,000 live births, 1st symptoms appear when the baby is first weaned and begins to ingest sucrose or fructose
   
   fructose-->fructose 1-phosphate via fructokinase, trapped
   
   accumulation of fructose 1-P, accumulation of free fructose in blood-->excreted in the urine (fructosuria), Pi depletion-->decrease ATP-->stimulate glycolysis & lactate production--> lactic acidosis, hypoglycaemia (sweating, confusion & sometimes seizures & coma), protein synthesis in the liver compromised, decrease production of essential proteins e.g. albumin, clotting factors drops, may often present with jaundice, icterus & hepatosplenomegaly
3. Genetic disorder involving ABC-transporter
4. from severe thiamine deficiency-->interruption of PDH complex, identified in 19th century in Asia from consumption of polished rice (no husk)
   Two types -wet and dry distinguished by the presence or absence of oedema
   advanced neuromuscular and cardiovascular disorders, delirium, muscle weakness and wasting, memory loss, ophthalmoplegia (paralysis of the eye muscles), peripheral vasodilation, increased venous return to the heart, death from high-output cardiac
5. >200 mutations, reduced synthesis of β-haemoglobin chain that results in microcytic hypochromic anaemia
   
   mutations generate additional splice sites within the mRNA, frame shifts or premature stop codons are introduced into the mature mRNA, results in the production of abnormal β-globin protein

5 Matching Questions

1. glucose 6-phosphate dehydrogenase deficiency
2. Ehlers-Danlos Syndrome (EDS)
3. Type VI Hers Disease
4. Type O hepatic glycogen synthase deficiency
5. scurvy

1. a glycogen storage disease, liver glycogen phosphorylase deficiency, leading to hepatomegaly (no splenomegaly), hypoglycaemia is less severe than in Type 1, no acidosis, no hyperlipidaemia, mental development normal, overall prognosis good
   
   symptoms are similar to Type I, often confused with mild cases of Type I
2. b enzyme used to reduce NADP+ to NADPH for antioxidation reactions, deficiency in antioxidation may lead to haemolytic anemia
   
   more than 400 mutations, some asymptomatic, may develop haemolytic deficiency caused by precipitating factors such as oxidant, drugs, favism, infection, neonatal jaundice,
   
   genetic x-linked disease
3. c a group of inherited disorders that disrupt collagen synthesis, affects connective tissues: skin, joints, blood vessel walls, 6 major types
   
   generally have deficiencies in collagen-processing enzymes e.g., lysyl-hydroxylase or pro-collagen peptidase, mutant collagen α chains (Type I, III & V), haploinsufficiencies
4. d vitamin C deficiency, prevent hydroxylation of lyysine and prolines-->interchain hydrogen bonding reduced
   
   subcutaneous extravascation of blood due to capillary fragility
5. e unable to synthesize glycogen, not specifically glycogen storage disease, tendency towards large blood glucose fluctuations between hypoglycaemia and hyperglycaemia

5 Multiple Choice Questions

1. lysosome storage disease, mutation in gene encoding a lysosomal hydrolase-->defective lysosomal hydrolase--> accumulation of GAG in various tissues (liver, spleen, bone skin and CNS)
   1. Cystic fibrosis
   2. Multiple Sclerosis
   3. Classic Galactosaemia
   4. mucoploysaccharidoses (MPS)
2. Genetic disorder involving ABC-transporter
   1. Tangier disease
   2. Gaucher's disease
   3. Parkinsons Disease
   4. lipidoses
3. Genetic disorder involving ABC-transporter, failure to pump out plant sterol back into gut lumen
   1. β-thalassemia
   2. haemolytic anaemia
   3. steatorrhoea
   4. Sitosterolaemia
4. common life threatening disease of PNS, large accumulation of lymphocytes, macrophages and plasma cells in nerve fibers, loss of muscle coordination & cutaneous sensation
   1. Zellweger's syndrome
   2. barth syndrome
   3. Marfan's Syndrome
   4. Guillain Barre Syndrome
5. deficiencies in the synthesis of Type I Collagen,
   
   8 recognized forms -Type I to VIII (Type I is the mildest, type II is the severest), COL1A1 and COL1A2 mutations (responsible >90% of all cases)
   1. Osteogenesis imperfecta-'imperfect bone formation'
   2. Osteogenesis imperfecta Type I (OI tarda)
   3. Osteogenesis imperfecta Type II (congenita)
   4. Type IV Andersen's disease

5 True/False Questions

1. barth syndrome → accumulation of lysocardiolipin, intermediates of cardiolipin, plasmalogen
   cardiolipin needed for electron transport chain
   
   Recognised in 1970s causing infantile death, cardiomyopathy, neutropena (neutrophil dysfunction) and 3-methylglutaconic aciduria.
   
   Taz acyltransferase gene mutation that is involved in remodeling CL.

   True        False

2. glucose 6-phosphate dehydrogenase (G6PD) Deficiency → enzyme used to reduce NADP+ to NADPH for antioxidation reactions, deficiency in antioxidation may lead to haemolytic anemia
   
   more than 400 mutations, some asymptomatic, may develop haemolytic deficiency caused by precipitating factors such as oxidant, drugs, favism, infection, neonatal jaundice,
   
   genetic x-linked disease

   True        False

3. Cystic fibrosis → thick mucous obstruction of respiratory airways and pancreatic duct, fatal-progressive destruction of lungs and pancreas, death usually by 30 years
   
   mutations in the gene for the CFTR chloride channel (ATP dependent), ABC transporter defect, failure in chloride transport reduces the fluid produced by the epithelial cells of lung airways and pancreatic ducts
   
   in pancreas, dried and thickened mucous blocks pancreatic duct, preventing pancreatic secretions from reaching duodenum, leading to improper digestion and absorption of almost all nutrients, especially fat-->steatorrhoea, secretions trapped in pancreatic duct start to act on pancreas itself-->autodigestion of pancreas
   
   Most common mutation is a deletion of phenylalanine at position 508 of primary structure, causing a misfolding

   True        False

4. glycogenoses → lipid storage disease, deficient in Hexosamindase A leading to the accumulation of GM2-ganglioside, disorders of ganglioside breakdown, accumulate in the nerve cells of the brain
   
   autosommal recessive disorder (1 in 300,000), 1 in 28 Ashkenazi Jews carry defective gene, complex lipids containing ceramide accumulate (brain, skin & reticuloendothelial system), fatal neurodegenerative disorder with macrocephaly, loss of motor skills, macular cherry red spot

   True        False

5. Fructokinase Deficiency (Essential fructosuria) → galactose metabolism disorder, rarer then classical galactosaemia, deficient in galactokinase needed to convert galactose-->galactose 1-P
   
   drives galactose-->galactitol via aldose reductase-->galactitol build up-->cataracts
   
   causes galactosaemia & galactosuria

   True        False