Unit 1 Diseases Flashcards
Alcaptonuria
Type: inborn errors of metabolism
accumulation of homogentisic acid in the blood; damage to cartilage, heart, kidney
Phenylketonuria (PKU)
Type: inborn errors of metabolism
o Most common o Mutation of phenylalanine hydroxylase o Accumulation of phenylalanine (essential a.a. but becomes too large in quantity) o Excretion of phenylpyruvic acid o Autosomal recessive o Treat by diet modification • Low PHE diet o Especially during pregnancy, high PHE in mother would be toxic to fetus (can cross the placenta) o Linked to mental retardation
Down Syndrome
Trimsomy 21
o Most common cause of mental retardation o Clinical features: • Incidence: 1/700 live births • Short stature • Low set ears • Microcephaly • Mental retardation • Up slanting eyes • Short hands • Eye folds • Protruding tongue • Usually infertile o Multiple System Defects • Heart, brain, endocrine system (infertility), susceptibility to infectious disease, increased risk of leukemia • High frequency of Alzheimer disease o More problems arise as individual ages o Although most are infertile, some have been known to reproduce sexually
Patau syndrome
Trisomy 13
o Features: • Failure to thrive • Cleft lip and palate • Rocker bottom feet • Polydactyly - condition in which a person has more than five fingers per hand or five toes per foot. • “punched-out” scalp • small head • Heart defect
Edwards syndrome
Trisomy 18
o Incidence: ~1/8000 live births o Features: • Low birth weight • Small mouth/jaw • Ventricular septal defect • Hypoplasia of muscles • Prominent occiput • Low-set malformed ears • Rocker bottom feet • Crossed fingers (CHARACTERISTIC HAND SIGN)
Hereditary Non-Polyposis Colon Cancer (HNPCC)
o The most common form of hereditary colon cancer, can be caused by mutations in any one of the seven mismatch repair genes
o Mutations in these genes cause the so-called “mutator phenotype”
Ataxia Telangiectasia (A-T)
Defect in the replication stress response network
o Susceptible to lymphomas
o Ataxia (abnormalities of balance), dilation of blood vessels (telangiectases) in skin and eyes, chromosome abberations, immune dysfunction
o Sensitive to gamma irradiation
o Mutations in the gene ATM, a protein kinase that is important for replication stress response and regulates p53, causing its accumulation
Bloom syndrome
Defect in the replication stress response network
o Susceptible to carcinomas, leukemias and lymphomas
o Facial telangiectases, chromosome alterations
o Sensitive to mild alkylating agents
o Caused by mutations in the BLM gene, a RecQ helicase, that functions in replication stress response
Xeroderma pigmentosum (XP)
o Severe predisposition to skin cancers
o Seven genetic complementation groups have been identified associated w/ defective NER (nucleotide excision repair)
o Loss of function in XPV also results in XP, but is not associated w/ NER but w/ defects in lesion bypass of UV-induced damage
XXX Female
- Usually due to maternal meiosis I error
- Average to tall stature (other than this, no striking features that would indicate a chromosomal abnormality)
- Learning deficit possible
- Some fertility problems possible
- Often go undetected throughout life
- Generally have chromosomally normal children
- Look phenotypically female
XYY Male
• Failure of paternal meiosis • Tall stature • Normal intelligence • Normal fertility • Clinical indistinguishable from 46,XY o Clinically normal • No Y-inactivation • Often go undetected throughout life
Klinefelter syndrome
47,XXY
- 50% due to meiosis I error in father
- Tall stature and thin
- Infertility – usually due to hyalinized testicular tubules
- Some female characteristics may develop: female-like breast development
- Learning deficit possible
- Most common reason for referral: post pubertal hypogonadism
Turner syndrome
45,X
- Most commonly recognized sex chromosome aneuploidy with a female phenotype
- Highly variable phenotypes
- Short stature
- Webbed neck
- At birth, edema of the hands and feet; after birth – short hands and fingers
- Heart and renal anomalies
- Increased carrying angle of the elbow (cubitus vulgas)
- Shield chest
- Low posterior hairline
- Usually normal intelligence, though may have learning difficulties
- Gonadal dysgenesis, primary amenorrhea (no menses)
- Usually infertile (but not always)
XY Female
- Y chromosome is intact, and the TDF is present and functional
- Androgen insensitivity
- Mutation of the androgen receptor gene located on the long arm of the X chromosome
- Infertility (female with testes)
XX “Male”
• Congenital adrenal hyperplasia (CAH)
• Mutation results in overproduction of androgens in female fetus
• Chemical imbalance
Treatable
