Term
| I-Cell Disease (inclusion cell disease)5 |
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Definition
Presentation: coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes, often fatal in childhood
Pathophys: Inherited lysosomal storage disease. Failure of addition of mannose-6-phosphate to lysosome proteins (enzymes secreted outside cell instead of targeted to lysosome) |
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Term
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Definition
Presentation: recurrent pyogenic infection, partial albinism, peripheral neuropathy
Pathophys: microtubule polymerization defect resulting in decreased phagocytosis |
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Term
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Definition
| Presentation: male and female infertility (sperm immotile), bronchiectasis, recurrent sinusitis (bacteria & particles not pushed out); associated with situs inversus |
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Term
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Definition
Presentation: Hyperextensible skin, tendency to bleed (easy bruising), hypermobile joints
Pathophys: Faulty collagen (usu. Type III) synthesis (ex. deficiency in lysyl oxidse mediated cross-linkage of collagen fibrils) Inheritance and severity vary. Can be autosomal dominant or recessive. Can be associated with joint dislocation, berry aneurysms, organ rupture. |
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Term
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Definition
Presentation: multiple fractures with minimal trauma, blue sclerae (translucency of connective tissue over choroid), hearing loss (abnormal middle ear bones), dental imperfections (lack of dentin)
Pathophy: Autosomal dominant with abnormal type I collagen. Variety of gene defects. |
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Term
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Definition
Presentation: Progressive hereditary nephritis, deafness. May be associated with ocular disturbances.
Pathophys: X-linked recessive. Variety of gene defects resulting in abnormal Type IV collagen. |
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Term
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Definition
Presentation: Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia
Pathophys: Deletion of normally active Paternal allele on chromosome 15 (maternal gene is normally imprinted) |
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Term
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Definition
Presentation: mental retardation, seizures, ataxia, inappropriate laughter ("happy puppet")
Pathophys: Deletion of normally active maternal allele on chromosome 15 (paternal allele imprinted normally) |
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Term
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Definition
Presentation: Short limbs, but head and trunk are normal size. Associated with advanced paternal age.
Pathophys: AD. Cell-signaling defect of fibroblast growth factor (FGF) receptor 3. |
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Term
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Definition
Presentation: Flank pain, hematuria, hypertension, progressive renal failure. Always bilateral, massive enlargement of kidneys due to multiple large cysts.
Pathophys: AD. 90% of mutations in APKD1 (chromosome 16). Associated with polycystic liver disease, berry aneurysms, mitral valve prolapse. Infantile form is recessive. |
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Term
| Familial adenomatous polyposis |
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Definition
Presentation: Colon becomes covered with adenomatous polyps after puberty. Progresses to colon cancer unless resected.
Pathophys: AD. Deletion of APC gene on chromosome 5. |
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Term
| Familial hypercholesterolemia (hyperlipidemia type IIA) |
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Definition
Presentation: Elevated LDL. Heterozygotes (1:500) have cholesterol=300mg/dL. Homozygotes (very rare) have cholesterol=700+mg/dL, severe atherosclerotic disease early in life and tendon xanthomas (classically in achilles tendon); MI may develop before age 20.
Pathphys: AD. Defective or absent LDL receptor.
Pathophys: |
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Term
| Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) |
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Definition
Presentation: telangiectasia, recurrent epistaxis, skin discolorations, ateriovenous malformations (AVMs).
Pathophys: AD. Inherited disorder of blood vessels. |
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Term
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Definition
Presentation: Hemolytic anemia.
Pathophys: AD. Spheroid erythrocytes due to spectrin or ankyrin defect; increased MCHC. Splenectomy is curative. |
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Term
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Definition
Presentation: depression, progressive dementia, choreiform movements, caudate atrophy and decrease levels of GABA and ACh in the brain.
Pathophys: AD. Trinucleotide repeat disorder: (CAG)n. Gene located on chromosome 4. Symptoms manifest between ages of 20 and 50. Anticipation can occur. |
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Term
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Definition
Presentation: tall with long extremities (eunichoid) pectus excavatum, hyperextensive joints and long, tapering fingers and toes (arachnodactyly); cystic medial necrosis of aorta --> aortic incompetence and dissecting aortic aneurysms; floppy mitral valve. Subluxation of lenses.
Pathophys: AD. Fibrillin gene mutation--> connective tissue disorder affecting skeleton, heart and eyes. |
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Term
| Multiple endocrine neoplasias (MEN) |
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Definition
Presentation: several distinct syndromes (I, II, III) characterized by familial tumors of endocrine glands, including those of the pancreas, parathyroid, pituitary, thyroid and adrenal medulla. MEN I: pituitary, parathryoid, pancreas. MEN II: parathryoid and pheochromocytoma. MENIII: pheo.
Pathophys: AD. MEN II and III associated with ret gene. |
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Term
| Neurofibromatosis type I (von Reclinghausen's disease) |
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Definition
Presentation: cafe-au-lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas). Also marked by skeletal disorders (eg. scoliosis), optic pathway gliomas, pheochromocytoma and increased tumor susceptibility.
Pathophys: AD. On long arm of chromosome 17. |
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Term
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Definition
Presentation: bilateral acoustic neuroma, juvenile cataracts.
Pathophys: AD. NF2 gene on chromosome 22. |
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Term
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Definition
Presentation: facial lesions (adenoma sebaceum), hypopigmented "ash leaf spots" on skin, cortical and retinal hamartomas, seizures, mental retardation, renal cysts and renal angiomyolipomas, cardiac rhabdomyomas, increase incidence of astrocytomas.
Pathophys: AD. Incomplete penetrance, variable presentation. |
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Term
| von Hippel-Lindau disease |
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Definition
Presentation: hemangioblastomas of retina/cerebellum/medulla; about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors.
Pathophys: AD. associated with deletion of VHL gene (tumor suppressor) on chromsome 3 (3p). Results in constituive expression of HIF (transcription factor) and activation of angiogenic growth factors. |
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Term
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Definition
Presentation: chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption and steatorrhea), meconium ileus in newborns, infertility in males (bilateral absence of vas deferens).
Pathophys: Autosomal recessive defect on CFTR gene on chromosome 7 commonly deletion of Phe 508. CFTR channel actively secretes Cl- in lungs and GI tract and actively reabsorbs Cl- from sweat. Defective Cl- channel-->secretion of abnormally thick mucus that plugs lungs, pancreas and liver-->pulmonary infections (pseudomonas and s.aureus). Diagnosis is via chloride sweat test. Treatment is with N-acetylcysteine. |
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Term
| Autosomal-recessive diseases |
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Definition
| Albinism, ARPKD (infantile polycystic kidney dz), CF, glycogen storage dzs, hemochromatosis, mucopolysaccharidoses (except Hunter's), phenylketonuria, sickle cell anemias, sphingolipidoses (except Fabry's), thalessemias |
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Term
| X-linked recessive disorders |
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Definition
| Bruton's agammaglobulinemia, Wiskott-Aldrich syndrome, Frgaile X, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne's and Becker's muscular dystrophy, Hemophilia A and B, Fabry's disease, Hunter's syndrome,. Female carriers rarely affected (random x inactivation) |
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Term
| Duchenne's Muscular Dystrophy |
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Definition
Presentation: Pelvic girdle muscle weakness progressing superiorly. Pseudohypertrophy of calf muscles (fibrofatty replacement of muscle). Cardiac myopathy. Use of Gowers' maneuver, requiring assistance of upper extremities to stand up is characteristic. Onset before 5 years of age.
Pathophys: X-linked frame-shift mutation-->deletion of dystrophin gene-->accelerated muscle breakdown.
Dystrophin helps anchor muscle fibers primarily in skeletal and cardiac muscle. Diagnose by increased CPK and muslce biopsy. |
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Term
| Becker's muscular dystrophy |
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Definition
| Less severe than Duchenne's. Onset in adolescence or early adulthood. |
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Term
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Definition
Presentation: 2nd most common cuse of genetic mental retardation, macro-orchidism (enlarged testes), long face with a large jaw, large everted ears, autism.
Pathophys: X-linked defect affecting the methylation and expression of the FMR1 gene. Associated with chromosomal breakage. Trinucleotide repeat disorder. |
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Term
| Trinucleotide repeat expansion diseases |
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Definition
| Huntington's disease, myotonic dystrophy, Friedreich's ataxia, fragile X syndrome. Huntington's disease = (CAG)n. MyoTonic dystrophy = (CTG)n. FraGile X syndrome = (CGG)n. Friedreich's ataxia = (GAA)n |
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Term
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Definition
Findings: mental retardation, flat facies, prominent epicanthal folds, simian crease, gap between 1st 2 toes, duodenal atresia, congenital heart disease (commonly ASD). Associated with increased risk of ALL and Alzhemier's dz (>35yo).
Pathophys: Trisomy 21. 95% of cases due to meiotic nondisjunction of homologous chromosomes (associated with advanced maternal age). Diagnose with quad screen (dec AFP, inc B-hCG, dec estriol, inc inhibin A). Ultrasound shows inc nuchal translucency. |
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Term
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Definition
Findings: severe mental retardation, rocker-bottom feet, micrognathia (small jaw), low-set ears, clenched hands, prominent occiput, congenital heart disease. Death usually occurs within 1 year of birth.
Pathophys: Trisomy 18 |
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Term
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Definition
Findings: severe mental retardation, rocker-bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoProsenscephaly, Polydactyly, congenital heart disease, Death usually occurs within 1 year of birth.
Pathophys: Trisomy 13 (puberty) |
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Term
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Definition
Findings: microcephaly, moderate to severe mental retardation, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities
Pathophys: congenital microdeletion of short arm of chromosome 5 |
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Term
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Definition
Findings: distinctive "elfin" facies, mental retardation, well-developed verbal skills, cheerful disposition, extreme friendliness with strangers, cardiovascular problems.
Pathophys: Congenital microdeletion of long arm of chromosome 7 |
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Term
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Definition
Presentation: variable, including cleft plaate, abnormal facies, thymic aplasia--> Thymic aplasia, cardiac defects, hypocalcemia sec. to parathyroid aplasia.
Pathophys: DiGeorge syndrome-thymic, parathyroid, cardiac defects
Velocardiofacial- palate, facial, and cardiac defects. CATCH-22 |
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Term
| Rate-determining enzymes of metabolic processes |
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Definition
Glycolysis = Phosphofructokinase-1 (PFK-1)
Gluconeogenesis = Fructose bisphosphatase-2
TCA cycle = Isocitrate dehydrogenase
Glycogen synthesis = Glycogen synthase
Glycogenolysis = Glycogen phosphorylase
HMP shunt = Glucose-6-phosphate dehydrogenase (G6PD)
De novo pyrimidine synthesis = Aspartate transcarbamoylase (ATCase)
De novo purine synthesis = Glutamine-PRPP amidotransferase
Urea cycle = carbamoyl phosphate synthase (CPS)
Fatty acid synthesis = Acetyl-CoA carboxylase (ACC)
Fatty acid oxidation = Carnitine acyltranferase I
Ketogenesis = HMG-CoA synthase
Cholesterol synthesis = HMG-CoA reductase |
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Term
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Definition
Presentation: hypoglycemia, jaundice, cirrhosis, vomiting
Pathophys: Hereditary deficiency of aldolase B. Autosomal recessive. Fructose-1-phosphate accumulates-->decrease in available phosphate-->inhibition of glycogenolysis and gluconeogenesis
Tx: decrease intake of both fructose and sucrose (glucose + fructose) |
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Term
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Definition
Presentation: benign, asymptomatic condition.
Pathophys: Defect in fructokinase. Autosomal recessive. Fructose does not enter cells but may appear in blood and urine. |
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Term
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Definition
Presentation: failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation
Pathophys: absence of galactose-1-phosphate uridyltransferase. Autosomal recessive. Damage caused by accumulation of toxic substances (eg. galactitol accumulates in lens of the eye).
Tx: Exclude galactose and lactose from diet. |
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Term
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Definition
Presentation: relatively mild. galactose appears in blood and urine, infantile cataracts. may initially present as failure to track objects or develop a social smile.
Pathophys: hereditary deficiency of galactokinase. autosomal recessive. galactitol accumulates if galactose is present in diet. |
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Term
| Ornithine transcarbamoylase (OTC) deficiency |
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Definition
Presentation: orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia (tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision)
Pathophys: most common urea cycle disorder. x-linked recessive. interferes with body's ability to eliminate ammonia. often in first few days of life, but sometimes late onset. excess carbamoyl phosphate is converted to orotic acid. |
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Term
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Definition
Presentation: orotic acid accumulates and spills into urine as crystals, megaloblastic anemia (doesnt improve with administration of vit B12 or folic acid), failure to thrive. No hyperammonemia (vs OTC deficiency)
Pathophys: autosomal recessive. defect of phophoribosyltransferase or orotidine 5' phosphate decarboxylase, two enzymes that convert orotic acid to uridine monophosphate. Lack of pyrimidine impairs nucleic acid synthesis needed for hematopoiesis.
tx: oral uridine administration |
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Term
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Definition
Presentation: mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor (aromatic aa)
Pathophys: autosomal recessive. due to decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor. Tyrosine becomes essential. Increased phenylalanine leads to excess phenylketones in urine.
Tx: decrease phenylalanine in diet and increase tyrosine. |
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Term
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Definition
Findings in infant: microcephaly, mental retardation, growth retardation, congenital heart defects
Pathophys: lack of proper dietary therapy during pregnancy |
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Term
| Alkaptonuria (ochronosis) |
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Definition
Findings: benign disease. dark connective tissue, pigmented sclera, urine turns black on standing, may have debilitating arthralgias.
Pathophys: autosomal recessive. congenital deficiency of homogentisic acid oxidase in degradative pathway of tyrosine. |
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Term
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Definition
Presentation: lack of melanin. results in increased risk of skin cancer.
Pathophys: congenital deficiency of tyrosinase (inability to synthesize melanin from tyrosine)-autosomal recessive OR defective tyrosine transporters (decreased amounts of tyrosine and thus melanin). variable inheritance due to locus heterogeneity (vs. ocular albinism- x-linked recessive). can result from lack of migration of neural crest cells. |
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Term
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Definition
Presentation: increased homocysteine in urine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), and atherosclerosis (stroke and MI)
Pathophys: 3 forms (all AR)
1. cystathionine synthase deficiency (tx: decrease Met and increase Cys and increase B12 and folate in diet)
2. decreased affinity of cystathionine synthase for pyridoxal phosphate (tx: increase vitamin B6 in diet)
3. homocysteine methyltransferase deficiency
All result in excess homocysteine and cystine becomes essential. |
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Term
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Definition
Presentation: cystine kidney stones (cystine staghorn calculi)
Pathophys: hereditary defect of renal tubular amino acid transporter for cysteine, ornithine, lysine, and arginine in the PCT of the kidneys. autosomal recessive, common. Tx: acetazolamide to alkalinize urine. |
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Term
| Maple syrup urine disease |
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Definition
Presentation: severe CNS defects, mental retardation and death. increased a-ketoacids in the blood, esp. Leu. Urine smells like maple syrup.
Pathophys: decreased alpha-ketoacid dehydrogenase. blocked degradation of branched amino acids (Ile, Leu, Val). |
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Term
| Adenosine deaminase deficiency |
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Definition
presentation: one of the major causes of scid (severe combined immunodeficiency disease. x-linked recessive.
pathophys: excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase-->prevents DNA synthesis and thus decreased lymphocyte count.
excess ATP and d |
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Term
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Definition
Presentation: retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
Pathophys: absence of HGPRT results in defective purine salvage leading to excess uric acid proguction. x-linked recessive. |
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Term
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Definition
Presentation: retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis
Pathophys: absence of HGPRT results in defective purine salvage leading to excess uric acid proguction. x-linked recessive. |
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Term
| Von Gierke's disease (type I) |
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Definition
Presentation: severe fasting hypoglycemia, increased glycogen in liver, increased blood lactate, hepatomegaly
Pathophys: deficient enzyme glucose-6-phosphatase (glucose-6-phosphate-->glucose) |
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Term
| Pompe's disease (type II) |
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Definition
Presentation: cardiomegaly and systemic findings leading to early death
Pathophys: lysosomal a-1,4-glucosidase (acid maltase). |
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Term
| Cori's disease (type III) |
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Definition
Presentation: milder form of type I with normal blood lactate levels.
Pathophys: deficiency of debranching enzyme (a-1,6-glucosidase) (limit dextran-->glucose) |
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Term
| McArdle's disease (type V) |
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Definition
Presentation: increased glycogen in muscle but cannot break it down, leading to painful muscle cramps, myoglobinuria with strenous exercise
Pathophys: deficien skeletal muslce glycosge phosphorylase McArdle's = Muscle |
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Term
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Definition
Findings: Peripheral neuropathy of hands/feet, angiokeratomas, cardivascular/renal disease
Pathophys: a-galactosidase A (accumulated substrate: ceramide trihexoside). XR |
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Term
| Gaucher's disease (most common) |
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Definition
Findings: Hepatosplenomegaly, aseptic necrosis of femur, bone crises, Gaucher's cells (macrophages that look like crumpled tissue paper).
Pathophys: Deficient B-glucocerebrosidase (accumulated: glucoscerbroside). AR |
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Term
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Definition
Findings: progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cells
Pathophys: deficient enzyme sphingomyelinase, accumulated substrate sphingomyelin. AR |
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Term
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Definition
Presentation: progressive neurodegeneration, developmental delay, cherry-red spot on macule, lysosomes with onion skin.
Pathophys: deficient enzyme-hexosaminidase A. accumulated substrate-GM2 ganglioside. AR. |
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Term
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Definition
Findings: peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Pathophys: deficient-galactocerebrosidase. accumulated-galactocerebroside. AR. |
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Term
| Metachromatic leukodystrophy |
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Definition
Presentation: central and peripheral demyelination with ataxia, dementia.
Pathophys: deficient-arylsulfatase A. accumulated-cerebroside sulfate. AR. |
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Term
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Definition
Presentation: developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
Pathophys: deficient a-L-iduronidase. accumulated substrate-heparan sulfate, dermatan sulfate. AR. |
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Term
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Definition
Presentation: Mild Hurler's + aggressive behavior, no corneal clouding
Pathophys: Deficient in Iduronate sulfate. accumulated substrate heparan sulfate, dermatan sulfate. XR. |
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Term
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Definition
Type I (hyperchylomicronemia): increased chylomicrons. Elevated TG and cholesterol in blood. Pathophys: Lipoprotein lipase deficiency or altered apolipoprotein C-II
Type IIa (familial hypercholesterolemia): increased LDL. elevated cholesterol. pathophys: Autosomal dominant; absent or decreased LDL receptors.
Type IV (hypertriglyceridemia): increased VLDL. elevated TG. Pathophys: hepatic overproduction of VLDL. |
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Term
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Definition
Findings: failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness
Pathophys: hereditary inability to synthesize lipoproteins due to deficiencies in in apoB-100 and apoB-48. Autosomal recessive. sx appear in first few months of life. |
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