- Role of maternal serum AFP in screening .

 Role of maternal serum AFP in screening .

Elevated Maternal Serum Alpha-Fetoprotein (MSAFP) levels act as a screening marker rather than a definitive diagnosis. It indicates that further investigation is needed to determine the exact cause.

VIRAL CROUP

Def.: heterogeneous group of mainly acute and infectious upper airway obstruction processes that are characterized by a barking like or brassy cough and may be associated with hoarseness, inspiratory stridor, and respiratory distress.

It is acute laryngotracheitis, Laryngotracheobronchitis!

Incidence:

·       The most common form of acute upper respiratory obstruction.

·       Affect about 15% of children.

·       It is most common between 6 m΄ and 6 years of age, with a peak prevalence in the 2^nd year of life, rare over the age of 10 years.

·       Boys > girls.

·       Season; a peak in autumn and winter is associated with parainfluenza virus but can occur throughout the year.

·       Croup is uncommon < 6 months of life.

·       Rarely lasts more than 10 to 14 days.

·       Approximately 15% of patients have a strong FHx of croup.

ETIOLOGY:

·       Parainfluenza viruses type 1 , 2 and 3 (account for ≈75% of cases(

·       Other viruses including RSV, adenovirus, influenza, and measles: Influenza has been associated with more severe cases.

Pathogenesis:

·       After inhalation of the virus, the cells of the local respiratory epithelium become infected.

·       There is marked edema of the lamina propria, submucosa, and adventitia accompanied by cellular infiltration with histiocytes, lymphocytes, plasma cells, and PNLs.

·       The infant’s glottis and subglottic region are normally narrow, and a small ↓ in diameter → large ↑ in airway resistance & ↓ in airflow.

- Chromosomes.

 Chromosomes

Each cell contains a nucleus within which there are several thread-like structures known as chromosomes, so called because of their affinity for certain stains. (Chroma = color   soma = body (

Chromosome: is DNA thread-like double-helix tightly coiled around histones.

Human somatic cells have 23 pairs of chromosomes (diploid number), with one copy of each chromosome inherited from each parent:

ü  22 pairs of chromosomes are autosomes;

ü  The remaining pair is called the sex chromosomes (XX in female or XY in male).

Human genetic material contains 3.1 billion bases.

Each germ cell contains 23 single chromosomes (haploid number):

ü  22 autosomes +

ü  1 sex chromosome ( x in ovum - Y or X in sperm)

 The non-dividing chromosome appears as thread-like structure which has:

·       Short arm (p) (for ‘petit’ or small)

·       constriction (centromere): localize genes and categorize chromosomes.

·       Long arm (q) (as next letter in the alphabet!)   .

Gene-based therapies

The treatment of most genetic disorders is based on conventional therapeutic approaches.

Gene therapy is an umbrella term for a number of techniques aimed at treating or preventing genetic disease.

The mechanisms of gene-based therapies include:

·       replacing the mutated copy of a gene with a functional copy, restoring protein function.

·       inactivating a mutated gene that has impaired function (‘knocking out’)

·       introduction of a new gene for the production of a beneficial protein.

There are a variety of types of gene therapy products, including:

1.   Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells.

2.  Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells.

3.  Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues.

4.    Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes.

5.   Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.

- Human DNA and RNA.

Human DNA

All nucleic acids are polynucleotides. A nucleotide consists of three components:

1.     A nitrogenous base: (Adenosine and guanine which are based on purine rings, Thymine and cytosine which are based on pyrimidine rings).

2.     A pentose sugar (deoxyribose in DNA and Ribose in RNA) at 3′ end

3.     1-3 phosphate groups at 5′ end

 There are two kinds of nucleic acids:

o   Deoxyribonucleic acid (DNA)

o   Ribonucleic acid (RNA).

•Two polynucleotide chains are linear but antiparallel (i.e. one chain runs in a 5' to 3' direction; the other runs 3' to 5').

•   The sugar and phosphate groups form the linear backbone of the strands with the bases projecting inwards towards their partners held together by hydrogen bonds between the opposing bases:

ü  Adenine (A) pairs only with thymidine (T) (2 hydrogen bonds)

ü  Guanine (G) pairs only with cytosine (C) (3 hydrogen bonds).

· Multiple fragments that, together with a protein skeleton (chromatin), form chromosomes.

· Site: Nucleus and Mitochondria.

- Indications of genetic testing!

Medical applications (indications of genetic testing, karyotyping, chromosomal culture, analysis) :

1.     Multiple congenital anomalies:

Birth defects > one developmental regions of the body

A.    Confirmation of a clinical diagnosis

B.    Estimate recurrence risk of future sibling

2.     Dysmorphic features or well-defined syndrome e.g down syndrome

3.     Unexplained Mental retardation (chromosomal abnormalities are responsible for 1/3  50% of MR which is due to genetic factor)   

4.     Pubertal failure

5.     Ambiguous genitalia

Provide diagnosis e.g turner, klinfilter

If Normal karyotyping → other endocrinal disorders

6.     Infertility: at least 5% of infertile men are killfilter.

7.     Recurrent spontaneous Abortions and miscarriage:

High anion gap metabolic acidosis mnemonic.

High anion gap metabolic acidosis mnemonic.

(RUSH Kill ME)

Renal tubular acidosis (distal), Rhabdomyolysis (massive)

Uremia

Salicylate ingestion

Hypovolemia, Heart failure

 

Ketoacidosis (diabetic, starvation)

Inborn error of metabolism, Iron, Isoniazid ingestion

Lactic acidosis

Late metabolic acidosis of prematurity

 

Mitochondrial diseases, Methanol ingestion

Ethanol, Ethylene glycol ingestion