Dr Shahida Mushtaq

 provides advanced understanding and applied knowledge in the theory and practice of Clinical Biochemistry  a critical understanding of how biochemical investigations are employed to develop a clinical diagnosis  Help you in developing necessary professional and research skills to promote lifelong learning and career development

 Disorders of Protein Metabolism:  Non-protein nitrogenous compounds (Urea, uric acid & amino acids):  Their normal plasma levels  Disease states associated with their increased and decreased levels in the plasma.  Plasma Proteins:  Normal and abnormal levels of plasma proteins and diseases associated with increased and decreased levels.  Immunochemistry  Components of the immune system.  Diseases associated with disorders in the immune system, multiple myeloma, systemic lupus erythromatosis, heavy-chain diseases, macroglobulinemia etc.

 Clinical Enzymology  Changes in enzymatic activity in disease states  Hemoglobin  Normal and types of abnormal hemoglobins.  Pathological cases associated with abnormal hemoglobin, e.g., thalassemia, sickle cell anemia etc.  Disorders of Lipid Metabolism  Hyper and hypolipoproteinemia.  Atherosclerosis & lipidoses.  Fatty liver.

 Disorders of Electrolytes, Blood Gases &Acid- base Balance  Sodium, potassium, chloride & their diagnostic value.  Gas transport in the blood (Oxygen & CO2).  Blood pH and its regulation.  Acidosis and alkalosis (Metabolic and respiratory) & Pathological conditions associated with each condition.

 Estimation of serum enzymes:  LDH and its isoenzymes.  CPK and its isoenzymes.  Aldolase  Leucine aminopeptidase.  Aspartate and Alanine Aminotransferases AST and ALT.  Serum glucose  Lipid profile

 Clinical Biochemistry, 2 nd Edition, 2008, R. Luxton.

 They arise from damaged gene leading to an abnormal enzyme.  They can affect many different biochemical pathways.  May be autosomal or sex linked.  Mutation in gametes and normal cells.

 They involve inheritance of abnormal gene from one or both parents and are linked with abnormal enzyme leading to defect in metabolic pathway.  There may be defects in other types of proteins for example cystic fibrosis.

 About 1300 diseases known so far.  About 100 start in the neonatal period  About 20 are amenable to treatment Incidence:  rare

 Suspect IEM in parallel to other common conditions e.g. Sepsis.  Non-specific signs and symptoms e.g. poor feeding, lethargy, failure to thrive.  Majority of cases may be sporadic.  Inborn errors of intoxication are usually amenable to treatment.

 Group 1: Disorders that give rise to Intoxication  Group 2: Disorders involving energy metabolism.  Group 3: Disorders involving complex molecules. (Proposed by JM Saudubray-2002)

This group includes IEM that lead to acute or progressive intoxication from accumulation of toxic compounds proximal to metabolic block.

Includes:  Aminoacidopathies e.g:  Phenylketoneuria (PKU)  Maple Syrup Urine Disease (MSUD)  Tyrosinaemia type I  Organic acidaemias e.g.  Methylmalonic acidaemia (MMA)  Propionic Acidaemia  Isovaleric Acidaemia

Includes (Cont):  Congenital Urea Cycle Defects  Arginosuccinate Lyase Def  Ornithine Carbamyl Transferase Def  Sugar Intolerance  Galactosaemia  Hereditary Fructose Intolerance

This group consists of IEM with symptoms due at least partly to a deficiency of energy production or utilization. They result from a defect in the:  Liver  Myocardium  Brain  Muscle

Includes:  Hypoglycaemic disorders  Gluconeogenesis defects  Glycogenosis defects  Hyperinsulinism  Fatty Acid Oxidation Disorders

Includes (Cont)  Congenital Lactic Acidaemias  Pyruvate carboxylase deficiency  Krebs Citric Cycle defects  Mitochondrial Respiratory Chain defects

This group includes diseases that involve defects in the synthesis or the catabolism of complex molecules. These diseases are:  Progressive  Permanent  Independent of intercurrent events  Not amenable to treatment.

Includes:  Lysosomal Disorders  Peroxisomal Disorders  Golgi Apparatus Disorders  Inborn Errors of Cholesterol Synthesis

 23 pairs of chromosomes  Autosomal or sex linked  Homozygous or heterozygous  inheritance pattern is different for both autosomal or sex linked genes.  Expression of gene depends on dominence of genes.

 An accumulation of the sustrate before enzyme defect.  Decrease in amount of product of enzyme.  An increased concentration of alternate metabolism  A decrease or absence of enzyme activity

 Screening for the IBEM in individuals who do not have symptoms.  Investigations of the patients with symptoms of the IBEM.

 Detecting a patient with an IBEM even before he shows overt symptoms of the disease  Screening should be done for high risk group  All newborn infants  Family of affected children  Expectant mothers who have previously had affected children (pre natal diagnosis)

 There is suitable treatment available for the disease  The disease is life threatening or seriously debelitating  The disease has relatively high incidence  A suitable test is available  The cost is acceptable.  PHENYLKETONURIA AND CONGENITAL HYPOTHYROIDISM

 Infant may present with symptoms within few days after birth or within few weeks of life.  Failure to thrive  Poor feeding  Persistent vomiting  Unexplained jaundice  Unexplained hypoglycemia  Ketosis  Lactic acidosis  Convulsions and coma  Lethargy  Hypotonia  hyperventilation

 Plasma  Electrolytes  Acid base balance  Blood gases  Glucose  LFT  Calcium

 Plasma  Insulin  lactic acid  Ammonia  ketones  Urine  Amino acid  Sugar  Organic acids

 Parents of the affected children  Amniocentesis  Fibroblasts recovered from amniotic fluid  Cultured and specific enzyme studies are performed  15 th week should be completed by 20 th week  CVS  9 th week complete within 10 days  DNA analysis  Cystic fibrosis