|gaucher's disease: deficiency of...accumulation of...||
|PKU: deficiency of...||
|Down's syndrome: endocrine problems||
|teratogen causing spina bifida||
-Lysosomal storage disease, AR-Deficiency in hexosaminidase A with accumulation of GM2 ganglioside-CNS degeneration, severe mental and motor deterioration-Blindness, cherry-red spot on macula-Death before age 4
|most chromosomal defects occur during...||
AR-Disorder of copper metabolism--Decreased serum ceruloplasmin-Liver disease varies from chronic hepatitis to cirrhosis-Kayser-Fleischer ring in eye-Involvement of basal ganglia (Extra-pyramidal signs)-Tx with penicillamine
AD-Slow progressive, nondisabling course with almost nl life expect.-Sequentially involves face, scapular area, humerus
|Glycogen Storage Diseases||
-autosomal recessive disorders resulting from defects in the synthesis or catabolism of glycogen.
-3 major groups
hepatic forms:prototype is vonv Gierke disease (type 1 glycogenosis)
results from deficiency of the heptaic enzyme glucose-6-phosphatase.
accumulation of glycogen because it cannot be broken down to free glucose
low blood glucose
myopathic forms:result from deficiencies of enzymes that fuel glycolysis in striated muscles
McArdle disease (type V glycogenosis), most important example, is caused by lack of muscle phosphorylase.
deficiency of enzyme leads to:storage of glycogen in skeletal muscles
muscle cramps after exercise
failure of exercise-induced rise in blood lactate
miscellaneous forms:there are several of these, the most important being type II glycogenosis (pompe disease)
results from deficiency of the lysosomal enzyme acid maltase.
many organs are involved, but storage of glycogen is mos prominent int he heart.
affected neonates have massive cardiomegaly, and death results from cardiac failure by 2 years of age.
|turner syndrome: heart problems||
1.Coarctation aorta2.aortic stenosis3.bicuspid aortic valve
|Down's syndrome: GI anomalies||
1.duodenal atresia2.Hirschsprung's disease
AR-Defic. in a-L-iduronidase, with accum. of heparan sulfate and dermatan sulfate in heart, brain, liver-Clinical: hsmegaly, dwarfism, stubby fingers, corneal clouding, MR-Death by 10-Very similar to Hunter syndrome, which is X-linked
Dwarfism. Shortened long bones of arms and legs but normal intelligence and head and trunk size. (DOMINANT DISORDER)
|autosomal dominant disorders||
mutations affect structural (collagen) or regulatory (receptor) proteins. in some instances the prodcut of the mutant allele interveres with the function of the normal protein (collagen). such mutant alleles, called dominant negative, can produce severe deficiency of protein, as in osteogenesis imperfecta.
there is a reduced penetrance and variable expressivity
onset of clinical features may be later than in autosomal recessive disorders
penetrance: the percentage of individuals carrying an autosomal dominant gene and expressing the trait
variable expressivity: variable expression of autosomal dominant trait in affect individuals
codominance: full expression of both alleles of a given gene pair in a heterozygote
polymorphism: multiple end effects of a single mutant gene
genetic heterogeneity: production of a given trait by different mutations at multiple loci.
|autosomal / sex-linked anomalies are more severe||
|coarse facial features + corneal clouding + CHD||
|tiptoe walking + seizures + inappropriate laughterdx?||
|How is PKU treated?||
1) Phenylalanine-free diet.
2) Screening tests for serum phenylalanine or urinary catabolites are usually performed on teh third or forth day of life.
3) Earlier screening may result in false-negative results.
|Cri du chat||
5p- (deletion)-Severe MR, microceph, cat-like cry, wide-set eyes
-AR-Incomplete metab. of phe and tyr d/t deficiency of homogentisic oxidase, leading to accum. of homogentisic acid-Urine turns dark when standing-Ochronosis - pigment of cartilage-Arthritis
AR-Glycogen storage type V-Defic. of muscle phosphorylase with accum. of glycogen in muscle-Painful cramps and muscle weakness following exercise
Caused by a nondisjunction of sex chromosomes. Individuals are female but instead of being XX, they only have one X chromosome. Results in having 45 chromosomes instead of 46. (CHROMOSOMAL ALTERATIONS)
|autosomal recessive disorders||
include most inborn errors of metabolism.
age of onset frequently early in life
clinical features tend to be more uniform
in many patients, enzyme proteins, rather than structural proteins, are affected
|What is Angelmen syndrome?||
1) Maternal transmission
2) Sometimes referred to as happy puppet.
3) Characterized by mental retardation, but is additionally characterized by ataxia, seizures, and inappropriate laughter.
X-linkedDefect in ability to mount an IgM response to capsular polysacch. of bacteria.Associated with high IgA levelsTriad of symptoms: Infections, purpura, eczema (WIPE)
X-linked; similar to Hurler's but not as severe-lysosomal storage disease-Def. in L-iduronosulfate resulting in accum. of heparan sulfate and dermatan sulfate-hsmegaly, micrognathia, retinal degeneration, joint stiffness, mild MR, cardiac lesions
|what are two disorders that result from defects in structural proteins?||
|OTC deficiency: dx test||
check orotic acid levels in urine
|What is Cori disease?||
1) Glycogen storage disease type III.
2) Caused by a deficiency of the debrancing enyme, amylo-1,6-glucosidase, leading to variable accumulation of glycogen in the liver, heart, or skeletal muscle.
3) Characterized by stunted growth, hepatomegaly, and hypoglycemia.
|What is familial hypercholesterolemia?||
1) Genetic defect characterized by anomalies of receptors for low-density lipoprotein.
2) Results in decreased transport of LDL cholesterol into cells, which causes hypercholesterolemia adn a striking increase in incidence and in earlier onset of atherosclerosis and its complications.
3) Further manifest by Xanthomas, raised yellow lesions filled with lipid-laden macrophages, in the skin and tendons.
|What are polygenic disorders?||
1) More common than monogenic disorders
2) Result from abnormalities of complex processes that are regulated by the protein products of two or more genes. Environmental factors also play an important role in the modulation of the genetic defects
3) Include such common entities as ischemic heart disease, diabetes mellitus, hypertension, gout, schizophrenia, bipolar disorder, and neural tube defects..
|What is female pseudohermaphrodite?||
Most often caused by increased androgenic hormones form congenital adrenal hyperplasia, an androgen-secreting adrenal or ovarian tumor in teh mother, or hormones administered to teh mother during pregnancy.
|Maple syrup urine disease||
-AR inborn error of metabolism-caused by defects to a-ketoacid dehydrogenase which means less degradation of branched AAs-Ile, Leu, Val build up (esp Leu)-MR, feeding problem, high urine levels of keto acids-Untreated leads to death
|What are 7 disorders that are associated with defects in enzymes?||
lysosomal storage diseases
tay-sachs disease (GM2-Gangliosidosis: Hexosaminidase alpha-subunit deficiency)
niemann-pick disease types A and B
glycogen storage diseases
|What is tuberous sclerosis?||
1) Characterized by teh presence of glial nodules and distorted neurons in teh cerebral cortex.
2) Marked by seizures, mental retardation, and adenoma sebaceum (a facial skin lesion consisting of malformed blood vessels and connective tissue)
3) Associated with rhabdomyomas of the heart and with renal angiomyolipomas, lesions consisting of malformed blood vessels, smooth muscle, and fat cells.
|What is Marfan syndrome?||
1) A defect of connective tissue characterized by faulty scaffolding.
2) apparently caused by a deficiency of fibrillin, a glycoprotein constituent of microfibrils.
3) Characterized by defects in skeletal, visual, and cardiovascular structures.
4) Patients are tall and thin with abnormally long legs adn arms, spider-like fingers, adn hyperextensible joints.
5) Dislocation of the ocular lens (ectopia lentis) is frequent.
6) Cystic medial necrosis can lead to aortic dilatin with resultant aneurysm of the proximal aorta, aortic valvular insufficieny, and dissecting aneurysm of the aorta. Loss of CT support may lead to mitral valve prolapse.
|List types of changes in chromosome number or structure.||
|How is cystic fibrosis manifested clinically?||
1) Chronic pulmonary disease; retention of viscid mucus, which leads to secondary infection; recurrent bouts of pneumonia, severe chronic bronchitis, bronchiectasis, and lung abscess are common. Infection with Pseudomonas aeruginosa is a common cause of death in cystic fibrosis.
2) Pancreatic insufficiency; deficiency of pancreatic enzymes that leads to malabsorptin and steatorrhea.
3) Meconium ileus; small-bowel obstruction in the newborn caused by thick, viscous meconium.
|What is Niemann-Pick disease?||
1) Most often caused by a deficiency of sphingomyelinase, with consequent sphingomyelin accumulation in phagocytes.
2) Characterized by "foamy histiocytes", containing sphingomyelin which proliferate in the iver, spleen, lymph nodes, and skin.
3) Marked by hepatosplenomegaly, anemia, fever, and, in some variants, by neurologic deterioration.
4) About half of the patients have a cherry-red spot in the macula similar to that of Tay-Sachs disease.
5) Death occurs by 3 years of age.
|What is autosomal dominant inheritance?||
1) One heterozygous parent carries a gene associated with phenotypic expression of a disorder adn the other parent is normal, by far the most likely case in nonconsanguineous matings.
2) One half of the children are expected to inherit the gene and are themselves heterozygotes who phenotypically manifest the gene.
3) Distribution of the phenotype is the same in both sexes.
|Familial Adenomatous Polyposis||
AD mutation of APC gene on 5q-Two hit hypothesis-Thousands of polyps, pancolonic, always involves rectum-Gardner's syndrome = FAP with osseous and soft tissue tumors, retinal hyperplasia-Turcot's syndrome - FAP with possible brain inv. (glioblastoma)
|What is von Gierke disease?||
1) Glycogen storage disease type I, or hepatorenal glycogenosis
2) Caused by a deficiency of glucose-6-phosphatase, with consequent accumulation of glycogen, primarily in the liver and kidney.
3) Characterized by hepatomegaly and sometimes by intractable hypoglycemia.
|What is type I Gaucher disease?||
Accounts for about 80% of cases, is characterized by hepatosplenomegaly, erosion of the femoral head and of the long bones, and mild anemia. Gaucher cells are seen in the liver, spleen, lymph nodes, and bone marrow. A normal life span is possible.
Psychological disorder, usually distressing but allows one to think rationally and function socially
Consciousness, awareness becomes separated from pervious memories, thoughts and feelings
Psychological disorders characterizied by frequent fearful thoughts about what might happen in the future
Contemporary perspective which assumes that biological, psychological and sociocultural factors combine and interact to produce psychological disorders.
|Patients with mental retardation have delays in development in ________ areas||
a psychological disorder characterized by enduring, inflexible, maladaptive patterns of behavior
Concept that diseases have physicaly causes that can be diagnosed, treated, and, in most cases, cured. When applied to psych disorders, assumes "mental" illnesses can be diagnosed on basis of symptoms and cured through therapy.
A catchall term used when schizophrenic symptoms either do not conform to the criteria of any one type of schizophrenia or conform to more than one type.
A period of excessive euphoria, inflatened self-esteem, wild optimism, and hyperactivity, often accompanied by delusions of gandeur and by hostility if activity is blocked
A condition characterized by loss of contact with reality
Mental processes and/ or behavior patterns that causes emotional distress and/ or substantial impairment in functioning
|What is Asperger's Disorder?||
An informat./exchange disorder with
1. Qualitative impairmnt in social interaction
2. Restricted repetitive & stereotyped patterns of behavior, interests & activities
3. but lack of clinically significant delay in language or cognitive development
a mood disorder marked by euphoria, hyperactivity, grandiose ideas, annoying talkativeness, unrealistic optimism, and inflated self-esteem
A dissociative disorder in which there is a complete or partial loss of the ability to recall personal information or identify past experience
|Gender indentity disorder||
Sexual disorder characterized by a problem accpeting one's identity as male or female
|antisocial personality disorder||
a personality disorder marked by impulsive, manipulative, often criminal behavior, without any feelings of guilt in the perpetrator
an anxiety disorder marked by sudden, unexpected attacks of overwhelming anxiety, often associated with the fear of dying or "losing one's mind"
Disorders with a sexual basis that are destructive, guilt- or anxiety-producing, complusive, or a cause of discomfort or harm to one or both parties involved
Question: True or False?
Each diagnostic group contains at least one Not Otherwise Specified Diagnosis
This is a true statement
Furman P. 12
|What is autistic disorder?||
A disorder characterized by abnormal functioning in at least one of 3 areas, with onset before age 3 years:
1) social interaction
2) language as used in social communication
3) symbolic or imaginative play
|borderline personality disorder (BPD)||
a personality disorder marked by impulsivity, unstable moods, an inconsistent sense of identity, and difficulty maintaining intimate relationships
|Major Depressive Disorder||
Mood disorder, which a person, for no reason, experiences 2 or more weeks of depressed moods, feelings of worthlessness adn diminshed interst or pleasure in most activities.
A marked fear of a specific object or situation; a general label for any phobia other than agoraphobia and social phobia
|What is diagnostic uncertainty?||
The variance in diagnosis that occurs for the clinician when he/she exercise his/her clinical judgment and interprets the presenting symptoms and other information
|seasonal affective disorder (SAD)||
a mood disorder in which severe depression arises during a particular season, usually the winter but sometimes the summer
|Question: Which 4 behaviors must be present for at least 6 months for Oppositional Defiant Disorder?||
1. Often loses temper
2. Often argues with adults
3. Often actively defies or refuses to comply with adult requests
4. Often deliberately annoys people
5. Often blames others for his/her mistakes or misbehavior
6. Is often touchy or easil.
|Question: What are the 4 major disorder groups?||
1. Intellectual & cognitive impairment
2. Motor function impairment
3. Disruptive or self injurious behavior
4. Information exchange
|What are pervasive developmental disorders?||
A broad based impairment or loss of function that would be expected for a child's age
|What are the sources of of diagnostic uncertainty||
1. natural variance
2. information variance
3. observation and interpretation
Furman p. 9
|What are 3 common problems of diagnosis?||
1. Patients who do not quite fit the criteria
2. Patients who fit the criteria for more than 1 disorder in the same category
3. patients who have symptoms of more than 1 psychiatric disorder