Term
Orotic aciduria
inheritance
defect
findings
treatment |
|
Definition
Autosomal Recessive
Can't convert orotic acid to UMP
Due to either lack of orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase
Increased orotic acid in urine, megaloblastic anemia, failure to thrive
Treat with oral uridine |
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Term
Adenosine deaminase deficiency
What is it
what clinical syndrome does it cause |
|
Definition
Excess ATP and not enough dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase thus inhibiting DNA synthesis
common cause of SCID |
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Term
Lesch-Nyhan Syndrome
inheritance
defect
findings |
|
Definition
X-linked recessive
No HGPRT so no conversion of hypoxanthine to IMP or guanine to GMP
retarded, self-mutilation/aggression, HYPERURICEMIA, gout choreoathetosis |
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Term
| What are the two amino acids that have only 1 codon for them? |
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Definition
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Term
|
Definition
| unable to perform nucleotide excision repair such as thymidine dimers from UV light |
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Term
| Hereditary nonpolyposis colorectal cancer |
|
Definition
| Unable to perform mismatch repair |
|
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Term
|
Definition
| Unable to perform non homologous end joining |
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Term
| What is the pathophysiologic mechanism by which Lupus affects gene expression? |
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Definition
| Lupus patients make antibodies against spliceosomal snRNPs |
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Term
Inclusion cell disease (I-cell disease)
defect
findings |
|
Definition
can't add M6P to lysosome proteins so they are secreted instead of trafficked to lysosome
Coarse facial features, clouded corneas, restricted joint movement and high plasma levels of lysosomal enzymes
often fatal in childhood |
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Term
Chediak-Higashi syndrome
defect
findings |
|
Definition
microtubule polymerization defect causing decreased fusion of phagosomes and lysosomes
recurrent pyogenic infections, partial albinism, peripheral neuropathy |
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Term
Kartagener's Syndrome
defect
findings |
|
Definition
dynein arm defect causes immotile cilia
infertility, bronchiectasis, recurrent sinusitis, situs inversus |
|
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Term
Osteogenesis Imperfecta
inheritance
defect
findings |
|
Definition
Autosomal dominant
Abnormal type 1 collagen
Multiple fractures with minimal trauma, blue sclerae, hearing loss, dental imperfections |
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Term
Ehlers-Danlos Syndrome
inheritance
defect
findings |
|
Definition
6 types, can be autosomal dominant or recessive
defect in type 3 collagen
hyper extensible skin, tendency to bleed/bruise, hyper mobile joints
associated with joint dislocation, berry aneurysm and organ rupture |
|
|
Term
Alport Syndrome
inheritance
defect
findings |
|
Definition
most likely X-linked recessive
abnormal type IV collagen
nephritis, deafness
may have ocular disturbances |
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|
Term
|
Definition
|
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Term
Alpha-1 Antitrypsin Deficiency
defect |
|
Definition
| lack alpha-1 antitrypsin results in excess elastase activity |
|
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Term
Achondroplasia
inheritance
defect
findings |
|
Definition
Autosomal Dominant
constitutively active FGF receptor 3 inhibits chondrocyte proliferation so less endochondal ossification (longitudinal growth) although membranous ossification (head/trunk) not affected)
dwarfism, short limbs
associated with advanced paternal age |
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|
Term
ADPKD
inheritance
defect
findings |
|
Definition
Autosomal Dominant
90% due to PKD1 (10% to PKD2)
multiple, large, bilateral renal cysts, may have polycystic liver disease, berry aneurysms and MVP |
|
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Term
Familial Adenomatous Polyposis
inheritance
defect
findings |
|
Definition
Autosomal Dominant
inactivating mutation of APC (a tumor suppressor)
thousands of polyps throughout the colon including rectum, eventually cancer |
|
|
Term
Familial hypercholesterolemia
(hyperlipidemia type IIa)
inheritance
defect
findings |
|
Definition
Autosomal Dominant
loss of LDL receptors
high LDL/TC (300+ if hetero, 700+ if homo) causes young MI, achilles tendon xanthomas and corneal arcus |
|
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Term
Osler-Weber-Rendu syndrome
inheritance
defect
findings |
|
Definition
Autosomal Dominant
blood vessels
telangiectasias, recurrent nose bleeds, skin discoloration, AVMs |
|
|
Term
Hereditary Spherocytosis
inheritance
defect
findings |
|
Definition
Autosomal dominant
mutated spectrin or ankyrin distorts RBC shape
hemolytic anemia, increased MCHC
treat with splenectomy |
|
|
Term
Huntington's Disease
inheritance
defect
findings |
|
Definition
Autosomal Dominant
increased CAG repeats in Huntingtin gene on chromosome 4
dementia, choreiform movements, caudate atrophy, decreases GABA and ACh
no symptoms before age 20-50 |
|
|
Term
Marfan's Syndrome
inheritance
defect
findings |
|
Definition
Autosomal Dominant
mutation in fibrillin a component of elastic fibers
tall with long extremities/fingers/toes, pectus excavatum, hyper extensive joints, cystic medial necrosis of aorta causing dissections, MVP, lens subluxation |
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|
Term
Multiple Endocrine Neoplasia 1
inheritance
defect
findings |
|
Definition
Autosomal Dominant
defect not known
pituitary tumors, prathyroid tumors, pancreatic (endocrine) tumors, kidney stones and ulcers |
|
|
Term
Multiple Endocrine Neoplasia 2A
inheritance
defect
findings |
|
Definition
Autosomal Dominant
ret gene
parathyroid tumors, pheochromocytomas, medullary thyroid tumors |
|
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Term
Multiple Endocrine Neoplasia 2B
inheritance
defect
findings |
|
Definition
Autosomal Dominant
ret gene
Oral/intestinal ganglioneuromatosis, pheochromocytomas, medullary thyroid tumors
associated with marfanoid habits |
|
|
Term
Neurofibromatosis 1
inheritance
defect
findings |
|
Definition
Autosomal Dominant
Mutated NF-1 gene on chromosome 17
cafe-au-lait macules, Lisch nodules (pigmented iris hamartomas), neurofibromas in skin, optic gliomas, pheochromocytoma |
|
|
Term
Neurofibromatosis 2
inheritance
defect
findings |
|
Definition
Autosomal Dominant
Mutated NF2 gene on chromosome 22
bilateral acoustic schwannomas, juvenile cataracts |
|
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Term
Tuberous Sclerosis
inheritance
findings |
|
Definition
Autosomal Dominant
HAMARTOMAS in CNS, Adenoma sebacem, Mitral regurg, Ash-leaf spots, cardiac Rhabdomyoma, Mental retardation, renal Angiomyolipima, Seizures
increased risk of astrocytoma
incomplete penetrance and variable presentation |
|
|
Term
von-Hippel-Lindau disease
inheritance
defect
findings |
|
Definition
Autosomal Dominant
deletion of VHL gene on chromosome 3 causing constitutive activation of HIF
hemangioblastomas of retina/cerebellum/medulla, cavernous hemagniomas of skin/mucosa/organs, pheochromocytoma |
|
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Term
Albinism
inheritance
defect
findings |
|
Definition
Autosomal recessive
Either deficiency of tyrosinase and can't synthesize melanin or defective tyrosine transporters so there is less tyrosine around
No skin pigmentation at all |
|
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Term
Ocular Albinism
inheritance
findings |
|
Definition
X-linked recessive
no pigment in the eyes only |
|
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Term
ARPKD
inheritance
defect
findings |
|
Definition
Autosomal recessive
defect unknown
infantile polycystic kidney disease, HTN, portal HTN and renal insufficiency
associated with congenital hepatic fibrosis and Potter's if renal failure in utero |
|
|
Term
Cystic Fibrosis
inheritance
defect
findings |
|
Definition
Autosomal Recessive
Deletion of Phe508 in CFTR gene on chromosome 7 leads to defective Cl- secretion in lungs and gut, defective reabsorption in sweat
thick mucous plugs in lungs, pancreas, liver causing pulm infections and pancreatic insufficiency, also nasal polyps, meconium ileus, infertility in males, increased Cl- in sweat |
|
|
Term
Hemochromatosis
Inheritance
defect
findings |
|
Definition
Autosomal Recessive
increased iron deposition
micronodular cirrhosis, diabetes, bronze skin, high ferritin, iron and transferrin saturation, low TIBC
leads to CHF, testicular atrophy, HCC |
|
|
Term
PKU
inheritance
defect
findings |
|
Definition
Autosomal recessive
no phenylalanine hydroxylase so no conversion of phenyalanine to tyrosine
retardation (mental and growth), seizures, fair skin, eczema, musty odor, PHENYLKETONES in urine |
|
|
Term
Malignant PKU
inheritance
defect
findings |
|
Definition
Autosomal recessive
no tetrahydrobiopterin (THB) cofactor so no conversion of phenylalanine to tyrosine or tyrosine to DOPA.
retardation (mental and growth), seizures, fair skin, eczema, musty odor, PHENYLKETONES in urine,
PKU THAT IS NOT ALLEVIATED BY TYROSINE |
|
|
Term
Sickle Cell Anemia
inheritance
defect
findings |
|
Definition
Autosomal recessive
glutamic acid instead of valine at position 6 of hemoglobin beta chain
extravascular hemolytic anemia, sickle cells, crew cut x-ray due to increased erythropoesis, sickle cell crises |
|
|
Term
Beta thalassemia
inheritance
defect
findings |
|
Definition
Autosomal Recessive
point mutations in splice sites and promoter causes hemoglobin beta chain to be underproduced
1 ALLELE AFFECTED: asymptomatic but increases HbA2
BOTH ALLELES AFFECTED: microcytic anemia, crew cut x-ray due to increased erythropoesis, basophilic stippling, target cells |
|
|
Term
Alpha thalassemia
inheritance
defect
findings |
|
Definition
Autosomal recessive
mutations cause decreased hemoglobin alpha synthesis
ALL 4 ALLELES AFFECTED: hydrops fetalis
3 ALLELES AFFECTED: microcytic anemia with basophilic stippling and target cells
1 OR 2 ALLELES AFFECTED: no significant anemia |
|
|
Term
Bruton's Agammaglobulinemia
inheritance
defect
findings |
|
Definition
X-linked recessive
defective BTK (tyrosine kinase) blocks pro-B cells from forming pre-B cells
recurrent bacterial infections after 6 months old, no thymus, low Ig of all classes, low B cells except pro-B |
|
|
Term
Wiskott-Aldrich Syndrome
inheritance
defect
findings |
|
Definition
X-linked Recessive
progressive deletion of B and T cells
TIE: Thrombocytopenic purpura, Infections, Eczema
Increased IgE and IgA, decreased IgM |
|
|
Term
Fabry's Disease
inheritance
defect
findings |
|
Definition
X-linked Recessive
missing alpha-galactosidase A causes ceramide trihexoside buildup
neuropathy of hands/feet, angiokeratomas (small red/blue marks), cardiovascular/renal disease |
|
|
Term
G6PD Deficiency
inheritance
defect
findings |
|
Definition
X-linked recessive
missing G6PD so less NADPH to detoxify free radicals and peroxides
hemolytic anemia when given fava beans, sulfa drugs, primaquine, TB drugs, or after infection
Heinz bodies, bite cells |
|
|
Term
Duchenne's Muscular Dystrophy
inheritance
defect
findings |
|
Definition
X-linked recessive
Deletion/frameshift in DMD gene reduces dystrophin so faster muscle breakdown
weakness in pelvic girlde muscles progressing superiorly, fattyfibrous calves, gower's sign, onset by 5, increased CPK |
|
|
Term
Becker's Muscular Dystrophy
inheritance
defect
findings |
|
Definition
X-linked recessive
missense mutation of dystrophin gene (DMD)
muscle weakness with an adolescent/early adulthood onset, increased CPK |
|
|
Term
Hunter's Syndrome
inheritance
defect
findings |
|
Definition
X-linked recessive
deficient iduronate sulfates leads to buildup of heparin and derma tan sulfate
aggressive behavior with mild Hurler's (developmental delay, gargoylism, airway obstruction, hepatosplenomegaly)
NORMAL CORNEA |
|
|
Term
Hemophilia A
inheritance
defect
findings |
|
Definition
X-linked recessive
F8 deficiency
increased PTT, hemarthroses, easy bleeding |
|
|
Term
Hemophilia B
inheritance
defect
findings |
|
Definition
X-linked recessive
F9 deficiency
increased PTT, hemarthroses, easy bruising |
|
|
Term
Fragile X Syndrome
inheritance
defect
findings |
|
Definition
X-linked Dominant
expanded CGG repeats affects methylation and expression of FMR1 gene
large testes/jaw/face/ears (inverted), retarded/autism, MVP |
|
|
Term
Friedreich's Ataxia
inheritance
defect
findings |
|
Definition
Autosomal Recessive
expansion of GAA repeats in gene frataxin impairs mitochondria
staggering gait, frequent falls, nystagmus, dysarthria, high arch in foot, hammer toes, hypertrophic cardiomyopathy
PRESENT IN CHILDHOOD WITH KYPHOSCOLIOSIS |
|
|
Term
|
Definition
|
|
Term
Down's Syndrome
defect
findings
screening results |
|
Definition
Trisomy 21
FLAT FACE, PROMINENT EPICANTHAL FOLDS, SIMIAN CREASE, retarded, gap between 1st 2 toes, duodenal atresia, heart defect
increased risk of ALL and alzheimer's
decreased AFP and estriol, increased inhibin A and HCG
increased nuchal translucency |
|
|
Term
Edward's Syndrome
defect
findings
screening results |
|
Definition
Trisomy 18
MICROGNATHIA, CLENCHED HANDS, rocker bottom feet, low-set ears, prominent occiput, congenital heart disease and retarded.
Usually dies before age 1
decreased AFP, estriol, HCG, normal inhibin A |
|
|
Term
Patau's Syndrome
defect
findings
screening results |
|
Definition
Trisomy 13
CLEFT LIP/PALATE, HOLOPROSENCEPHALY, POLYDACTYLY, rocker bottom feet, micropthlamia, microcephaly, congenital heart disease and retarded.
Usually die by age 1
normal AFP, estriol, HCG, and inhibin A. |
|
|
Term
Cri-du-chat syndrome
defect
findings |
|
Definition
micro deletion of short arm of 5
microcephaly, retarded, high pitched crying, epicanthal folds and VSD |
|
|
Term
Williams Syndrome
defect
findings |
|
Definition
micro deletion of long arm of 7 (elastin gene)
elf face, retarded, hypercalcemia, well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems |
|
|
Term
DiGeorge Syndrome
defect
findings |
|
Definition
micro deletion of 22q11 leads to aberrant development of 3rd and 4th branchial pouches
CATCH-22
Cleft palate, Abnormal face, THYMIC APLASIA (no T cells), CARDIAC DEFECTS, HYPOCALCEMIA (due to no PTH) |
|
|
Term
Velocardiofacial syndrome
defect
findings |
|
Definition
Microdeletion of 22q11
CATCH-22
CLEFT PALATE, ABNORMAL FACE, Thymic aplasia (no T cells), CARDIAC DEFECTS, Hypocalcemia (no PTH) |
|
|
Term
PDH Deficiency
inherited?
defect
findings
treatment |
|
Definition
can be congenital or acquired (B1 deficiency)
deficient PDH causes buildup of pyruvate and alanine leading to lactic acidosis
neurologic deficits
Treat with ketogenic diet |
|
|
Term
Chronic Granulomatous Disease
defect
findings |
|
Definition
NADPH deficiency, so unable to generate superoxide (Odot)
very susceptible to catalase positive bacterial infections (Staph Aureus, Aspergillus)
Able to use H2O2 from catalase negative bacteria to generate hypochlorite though |
|
|
Term
Essential Fructosuria
inheritance
defect
findings |
|
Definition
Autosomal recessive
Defective fructokinase, unable to convert fructose to Fructose-1P
Benign and asymptomatic since fructose does not normally enter cells |
|
|
Term
Fructose intolerance
inheritance
defect
findings
treatment |
|
Definition
Autosomal recessive
Deficiency of aldolase B, unable to metabolize F1P into DHAP or glyceraldehyde which accumulates and depletes phosphate stores thus inhibiting glycogenolysis and gluconeogenesis
hypoglycemia, jaundice, cirrhosis, vomiting
Treat with reduced intake of fructose and sucrose |
|
|
Term
Galactokinase Deficiency
inheritance
defect
findings |
|
Definition
Autosomal recessive
deficiency of galactokinase so galacitol accumulates if galactose present
galactosuria and galactosemia, infantile cataracts. Often presents as failure to track fingers or social smile. |
|
|
Term
Classic Galactosemia
inheritance
defect
findings
treatment |
|
Definition
Autosomal Recessive
absence of galactose-1-phosphate uridyltransferase so galacitol and other toxic substances accumulate
Failure to thrive, jaundice, hepatomegaly, infantile cataracts, retarded
Treat with low galactose and lactose diet |
|
|
Term
Alkaptonuria
inheritance
defect
findings |
|
Definition
Autosomal Recessive
No homogentisic acid oxidase so homogentisic acid deposits in cartilage changing their color and destroying them.
Dark connective tissue, brown pigmented sclera, urine turns black on exposure to air. May have debilitating arthritis |
|
|
Term
Gilbert's Syndrome
defect
findings
treatment |
|
Definition
mildly decreased UDP-glucoronyl transferase leads to decreased liver uptake of unconjugated bilirubin
Asymptomatic with elevated indirect bilirubin (gets worse with fasting or stress)
no treatment needed |
|
|
Term
Crigler-Najjar Syndrome, Type 1
defect
findings
treatment |
|
Definition
absent UDP-glucoronyl transferase causes a lack of bilirubin conjugation
jaundice, kernicterus, elevated indirect bilirubin
Treat with phototherapy and plasmapharesis
more severe than type 2 |
|
|
Term
Crigler-Najjar Syndrome, Type 2
defect
findings
treatment |
|
Definition
deficient UDP-glucoronyl transferase leads to decreased bilirubin conjugation
jaundice, kernicterus increased indirect bilirubin
Treat with phenobarbital
less severe than Type 1 |
|
|
Term
Dubin-Johnson Syndrome
defect
findings
treatment |
|
Definition
defective excretion of conjugated bilirubin
black liver, elevated direct bilirubin
asymptomatic, no treatment necessary |
|
|
Term
Rotor's Syndrome
defect
findings
treatment |
|
Definition
mildly defective liver excretion of conjugated bilirubin
elevated direct bilirubin
asymptomatic, no treatment needed |
|
|
Term
Fanconi's Anemia
inheritance
defect
findings
treatment |
|
Definition
Autosomal recessive
DNA repair defect leaving cells more susceptible to chromosomal breakage by DNA cross-linking agents
Thrombocytopenia or leukopenia progressing to pancytopenia (fatigue, mucosal bleeding) and bone marrow failure. Also see congenital defects like small testicles, radial hypoplasia and thumb deformity.
Treat with bone marrow transplant. |
|
|
Term
Maple Syrup Urine Disease
defect
findings |
|
Definition
Decreased a-ketoacid dehydrogenase causes buildup of Ile, Leu, and Val (branched chain AAs)
CNS defects, retarded, death, maple syrup smelling urine |
|
|
Term
Hartnup's Disease
inheritance
defect
findings |
|
Definition
Autosomal Recessive
defective neutral amino acid transporter in renal and intestinal epithelium
high tryptophan in urine and decreased absorption, leads to pellagra/B3 deficiency (diarrhea, dermatitis, dementia) |
|
|
Term
Type 1 Dyslipidemia
defect
what's increased
what blood tests are elevated
findings |
|
Definition
Lipoprotein lipase deficiency or altered apolipo-C2.
Chylomicrons
TG, cholesterol
pancreatitis, hepatosplenomegaly, xanthomas |
|
|
Term
Type 2a Dyslipidemia
inheritance
defect
what's increased
what lab tests are elevated
findings |
|
Definition
Autosomal dominant
absent or decreased LDL receptors
LDL
Cholesterol
Accelerated atherosclerosis, tendon (Achilles) xanthoams, corneal arcus |
|
|
Term
Type IV dyslipidemia
defect
what's increased
what lab tests are elevated
findings |
|
Definition
Hepatic overproduction of VLDL
VLDL
TG
pancreatitis |
|
|
Term
Ornithine Transcrbamoylase Deficiency
inheritance
defect
findings |
|
Definition
X-linked recessive
lack of OTC causes buildup of carbamoyl phosphate which becomes orotic acid
Find orotic acid in blood and urine, decreased BUN, hyperammonemia (tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurry vision) |
|
|
Term
Werdnig-Hoffman Disease
inheritance
defect
findings |
|
Definition
Autosomal Recessive
Degeneration of anterior horns
Floppy baby (LMN findings) with tongue fasiculations, 50% die by 7 months |
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