Page 1 of 2: GENETIC DISEASES-compact review for exam;add to it

tanmay_mehta · Credits: 16561 My Scrapbook My Reading List 3 Books

GENETIC DISEASES-compact review for exam;add to it

Cystic Fibrosis (CF)

Primary Defect
A defective protein disrupts the movement of salt and water across cell membranes. A primary effect of this is accumulation of thick mucus that interferes with lung and digestive function.

Screening Test
Immunoassay to measure the pancreatic enzyme immunoreactive trypsin (IRT) followed by DNA analysis for those with elevated levels. 3% to 5% false negative rate. Positive predictive value is nearly 100% when two defective genes are found, 5-10% when only a single defective gene is found (based on data from Wisconsin with DNA testing for the common mutation only).

Etiology & Prevalence
Genetic autosomal recessive. A single mutation (delta F508) is most common in Northern
Europeans and is associated with severe clinical outcomes. However, hundreds of other
mutations have been identified, some with more mild disease states. There is significant clinical variability, however, even among those with identical genetic defects.
Occurrence (and genotype) is highly variable among different populations. About 1 in 2000 Northern European, 1 in 17,000 African American and 1 in 9,000 Hispanic infants are affected. If Untreated Substantial impact on lung function, increased lung infections, and malnutrition due to abnormal production of pancreatic enzymes. Other features include cirrhosis of the liver, abnormal glucose tolerance, and infertility.

Therapy
Currently only palliative therapies are available. These are aimed primarily at maintaining lungfunction, preventing infection, and enhancing nutritional status.
With Treatment Improved treatments have dramatically increased life expectancy for affected individuals from approximately 3 years in the 1950’s to the late 30’s today. The impact of early detection through newborn screening is not fully understood, however. Improved nutritional status in early childhood has been shown, but the long-term benefits remain to be determined.

tanmay_mehta · Credits: 16561 My Scrapbook My Reading List 3 Books

Glucose-6-Phosphate Dehydrogenase Deficiency
(G-6-PD deficiency)

Primary Defect
Defect in the structure of the G-6-PD enzyme, which plays a role in protecting hemoglobin from oxidative damage leading to hemolysis.

Screening Test
Fluorescent spot test that measures G-6-PD enzyme activity.

Etiology & Prevalence
Genetic – X linked recessive, several hundred mutations have been described.
A defective gene is found in 1 in 50 Southeast Asians, 1 in 10 Mediterraneans (Italian, Greek, Middle Eastern) and 1 in 10 African Americans, less than 1 in 1,000 northern Europeans. The degree of enzyme deficiency is related to mutation involved and gender.
If Untreated Varies depending on residual enzyme activity. Most persons with deficiency never suffer any clinical manifestations. Mediterranean and Asian forms have greater deficiency with neonatal jaundice, and episodic hemolytic anemia prominent features. The African American form is less severe due to residual enzyme activity, although hemolytic anemia may occur. Hemolysis may be triggered by exposure to oxidant drugs or infections. Consumption of Fava beans can induce hemolysis in some with the Mediterranean forms.

Therapy
Phototherapy for neonatal jaundice. Avoidance of oxidant drugs such as antimalarials and
sulphonamides, and avoidance of fava beans for those with the Mediterranean forms.
Transfusion may be used to counteract severe episodes of jaundice or hemolysis.
With Treatment Resolution of jaundice in the newborn. Reduced incidence of hemolytic episodes.

tanmay_mehta · Credits: 16561 My Scrapbook My Reading List 3 Books

Galactosemia

Primary Defect
Deficiency in enzymes that help convert galactose into glucose. The body cannot use galactose directly.

Screening Test
Fluorescent assay for enzyme activity Typically followed by measurement of galactose if reduced activity is detected

Etiology & Prevalence
Genetic (autosomal recessive)
Occurs in about 1 in 50,000 births
If Untreated Jaundice, vomiting, lethargy, hepatosplenomegaly, cataracts and failure to thrive leading to liver failure, sepsis. Often fatal

Therapy
Galactose free diet for life with strict avoidance of lactose (milk sugar) and lactose containing foods.

With Treatment
Mortality avoided if detected in time; improved IQ if treated early but typically in the low end of normal; speech and learning disabilities are common; ovarian failure for most females.

tanmay_mehta · Credits: 16561 My Scrapbook My Reading List 3 Books

Homocystinuria

Primary Defect
Deficiency or absence of an enzyme necessary for the breakdown of the amino acid methionine results in build up of methionine in the blood and elevated excretion of homocystine in the urine.

Screening Test
Historically screening has been based on measurement of methionine in the dried blood spot using a bacterial inhibition assay similar to the original Guthrie assay for PKU. Screening is now possible using tandem mass spectrometry (MS/MS). Predictive value should be high. Because of delayed accumulation of methionine if residual enzyme activity is present, screening may be more effective at 2 to 4 weeks of age for these infants.

Etiology & Prevalence
Genetic, autosomal recessive. A number of specific genetic defects have been identified. With some, residual enzyme activity may occur, resulting in moderation of symptoms and delay in accumulation of elevated levels of methionine.
Prevalence estimates vary between 1 in 80,000 to 1 in 500,000. Possibly due to variation in sensitivity of the screening tests with age.
If Untreated there is wide variation in clinical course for affected infants. Clinical features include:
• circulatory blood clotting (thromoembolism), physical and mental developmental disabilities.
• Approximately half die by age 25 due to thromboembolism. Developmental delay and physical defects affect most. The most common defect (cystathionine ß-synthase deficiency) can be classified as either responsive or non-responsive to treatment with vitamin B6. This may be related to residual enzyme activity needed for response. Those who are not responsive have more severe clinical course.

Therapy
Vitamin B6 supplementation for those who are responsive. Dietary restriction of methionine with supplementation of cystine for those who are not. Other treatment focused on clinical features such as aspirin to combat thromboemblism.
With Treatment Mortality and mental retardation are prevented or reduced. Clinical variability of other features remains.

tanmay_mehta · Credits: 16561 My Scrapbook My Reading List 3 Books

Maple Syrup Urine Disease
(MSUD)

Primary Defect
Deficiency or absence of an enzyme needed to break down the branched chain amino acids, leucine, isoleucine, and valine. This results in increased serum levels of these amino acids and ketoacid intermediates.

Screening Test
Historically screening has been based on measurement of leucine in the dried blood spot using a bacterial inhibition assay similar to the original Guthrie assay for PKU. Screening is now possible using tandem mass spectrometry to measure the amino acids. Predictive values are not documented but should be high.

Etiology & Prevalence
Genetic, autosomal recessive. A number of specific genetic defects have been identified. With some, residual enzyme activity may occur, resulting in moderation of symptoms.
About 1 in 130,000 infants expected in Washington State. It occurs in about 1 in 760 births to Mennonite families.
If Untreated Lethal for the classical form (absent enzyme activity), usually in the first month of life. If residual enzyme activity is present, children develop mental and physical retardation.

Therapy
Dietary restriction of branched chain amino acids. Requires specialized medical and nutritional intervention. With Treatment Variable. Outcome is related to age and neurological symptoms at the time therapy is initiated. Treated infants may have retardation related to onset of symptoms before screening test results are communicated. Highly coordinated screening system is essential since irreversible damage or death can occur within the first two weeks of life.

tanmay_mehta · Credits: 16561 My Scrapbook My Reading List 3 Books

Congenital Toxoplasmosis

Primary Defect
Congenital infection by the protozoan Toxoplasmosis gondii (a parasite associated with cats and raw or undercooked meat)

Screening Test
Enzyme linked immunosorbent assay (ELISA) test of blood dried on filter paper for Ig-M
antibodies to T. gondii

Etiology & Prevalence
Infectious disease - Infection of fetus can occur if mother acquires infection during pregnancy (infection is transmitted across that placenta or, occasionally, during birth). Infections acquired early in pregnancy have more severe impact than those acquired late, however, those acquired late are more common.
Occurs in about 1 in 10,000 births
If Untreated Mental retardation, neurological impairment, severe visual impairment, some mortality (frequency is uncertain).

Therapy
Twelve to twenty four month course of treatment with combinations of antibiotics, notably pyrimethamine, sulfadiazine, spiramycin. Additional treatment may be needed to counteract toxicity of pyrimethamine.
With Treatment May stop acute infection and reduce damage to organs. Outcome appears to be improved but magnitude is not yet fully determined. Data from available studies is limited and the impact on long-term outcome is unclear.

tanmay_mehta · Credits: 16561 My Scrapbook My Reading List 3 Books

if u find above posts helpful, then contribute to it by posting basic info asked in mcqs about other imp genetic ds asked in exams.

thanx

pingu81 · Credits: 690 My Scrapbook

scid:3 types
1)major type is defect in gamma receptor of Tlymphocytes(IL-7)known to play a major role
2)adenosine deaminase deficiency

2shar · Credits: 7780 My Scrapbook

what is quadruple test in downs syndrome?

binnie · Credits: 565 My Scrapbook

Quadriple test for downs syndrome
- maternal serum inhibin assay + triple test
(beta HCG+ ms-AFP +unconjugated estriol )

		Sign In New User? Sign Up Sign in to access your control panel and messenger!
				TechZone \| SpiderNevi \| HowTo? \| Scrapbook!