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
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Help you in developing necessary professional and research skills to promote lifelong learning and career development

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

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

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Disorders of Electrolytes, Blood Gases &Acidbase Balance
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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.

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

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

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

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

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

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

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Group 1: Disorders that give rise to
Intoxication
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Group 2: Disorders involving energy metabolism.
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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:
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Aminoacidopathies e.g:
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Phenylketoneuria (PKU)
Maple Syrup Urine Disease (MSUD)
Tyrosinaemia type I
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Organic acidaemias e.g.
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Methylmalonic acidaemia (MMA)
Propionic Acidaemia
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Isovaleric Acidaemia

Includes (Cont):
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Congenital Urea Cycle Defects
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Arginosuccinate Lyase Def
Ornithine Carbamyl Transferase Def
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Sugar Intolerance
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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:
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Liver
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Myocardium
Brain
Muscle

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

Includes (Cont)
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Congenital Lactic Acidaemias
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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:
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Progressive
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Permanent
Independent of intercurrent events
Not amenable to treatment.

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

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

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

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

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

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

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

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Plasma
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Electrolytes
Acid base balance
Blood gases
Glucose
LFT
Calcium

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

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