Genetic and Metabolic Medicine

Question 1

Single copy of a set of chromosome

Answer 1

Haploid

Question 2

Three copies of a set of chromosome

Answer 2

Triploid

Question 3

Three copies of a single chromosome within a whole cell

Answer 3

Trisomy

Question 4

Define lyonisation

Answer 4

One of the two X chromosomes in every cell in a female is randomly inactivated early in embryonic development. - forms a Barr body

Question 5

Characteristics of X-linked dominant conditions

Answer 5

both sexes affected equally, often lethality in males and females less affected

Question 6

Explain trinucleotide repeat disorders with examples

Answer 6

Increasing numbers of repeats (show anticipation) eg) Myotonic dystrophy, Fragile X, Friedrichs Ataxia

Question 7

What is MELAS?

Answer 7

Mitochondrial Encephalopathy, Lactic Acidosis and stroke like episodes = mitochondrial inheritance

Question 8

What is MERRF?

Answer 8

Myoclonic epilepsy with Raggad Red Fibres = mitochondrial inheritance

Question 9

Tissues usually affected by mitochondrial disorders?

Answer 9

All tissues requiring a lot of energy (Brain, eyes, ears, kidneys)

Question 10

What is genomic imprinting? + Disorders

Answer 10

Epigenetic phenomenon leading to the exclusive expression of specific genes from only one parent. Disease = uniparental disomy (maternal) - Ch 15 Prader-Willi (paternal) - Ch 15 Angelmans

Question 11

Genetic syndromes associated with peripheral pulmonary stenosis? (x 2)

Answer 11

Alagile syndrome, Williams syndrome

Question 12

Genetic syndrome associated with Tetralogy of Fallot? (+ characteristics x 7)

Answer 12

Velocardiofacial Syndrome ~ DiGeorge Sx - 22q11 deletion - Tetralogy of Fallot - Cleft palate - Long face - Bulbous nose, abnormal ears - Short palpebral fissures - learning difficulty

Question 13

Genetic Syndrome associated with pulmonary stenosis? (+ other characteritstics

Answer 13

Noonan Syndrome

• broad webbed neck
• wide set eyes
• ptosis + epicanthic folds
• Micrognathia

Question 15

What is propionic acidaemia?

Answer 15

Rare metabolic disorder, affects all tissues

Increased risk of metabolic stroke (in basal ganglia) due to toxic metabolites due to deficiency in enzyme importat for protein breakdown

Seizures/encephalopathy, hypotonia, cardiomyopathy, pancreatitis, vision/hearing loss

Question 16

Neonatal jaundice, feeding difficulties, developmental delay, cataracts?

Answer 16

Galactosaemia

• caused by RBC galactose-1-phosphate (GALT) deficiency
• Unable to breakdown galactose
• picked up on newborn screen
• avoidance of galactose reduces developmental delay, can cause cataracts

Question 17

Gross motor regression at >3 months, macrocephally, cherry red macular, hyper-reflexia?

Answer 17

Tay-Sachs Disease

• lysosomal storage disorder from Chr 15 (AR)
• macrocephaly due to accuulation of GM2 in the brain and progressive neurological decline
• more common in Ashkenazi Jewish or French-Canadian descent

Question 18

What is a mucopolysacharidosis?

+ 3 main types

Answer 18

Defect in enzymes that break down GAGs (glycosaminoglycans) - defects due to accumulation of breakdown products

1) Hunters (MPS II - X-Rescessive) - normal vision, GDD, sinopulmonary infections, hepatosplenomegally
2) Morquio (MPS IV) - skeletal problems + cloudy cornea, normal intellect
3) Hurlers (MPS I)- GDD, sinopulmonar infections, hepatosplenomegally, cloudy cornea