Term
| Zellweger, neonatal adrenaoleukodystrophy, infantile fersum disease |
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Definition
P: refsum -> least sever, Zellweger -> most sever, high forehead, epicanthal folds, mental retardation, early lethality
inheritance: auto rec
mutation: peroxisome biogenesis factor genes (PEX)
Testing: absent peroxisomes, increased VLCFA
**peroxisomal |
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Term
| maple syrup urine disease |
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Definition
Phenotype: apenea, hypoglycemia, cerebral edema, poor feeding, vomit, maple syrup pee, muscle rigidity, seizure, no degrading of branched chain amino acids
Treatment: vitamin B12 (thiamine)
**AA disorder |
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Term
| adrenoleukodystrophy (x-linked) |
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Definition
phenotype: learning deficits, loss of hearing/vision, demyelinated cerebral hemispheres
inheritance: x-linked recessive
mutation: mutated ABCD1 gene leads to defective peroxisomal B oxidation of VL chain fatty acids
testing: look for unbranched saturated fatty acids with 24-30 carbons
treatment: restrict vlcfa, bone marrow transplant
**lorenzo's oil, peroxisomal disorder |
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Term
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Definition
phenotype: painful electrically-silent cramps (contractures, exercise intolerance, rhabdomyolysis/myogloburia
mutation: muscle phosphorylase deficiency -> no lactate production when exercising
** carbohydrate met. disorders |
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Term
| adenosine deaminase deficiency |
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Definition
phenotype: severe immunodeficiency with impaired T cells, rib cage abnormal, chnodro-osseuos dysplasia
inheritance: auto rec
mutation: mutated adenosine deaminase -> adenosine accumulation -> lymphocyte toxicity
testing: test for enzyme
treatment: 1990 first gene therapy by Dr. W. French anderson on 4 yo Ashanti DeSilva at the NIH
**Purine metabolism |
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Term
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Definition
phenotype: ocular lens dislocation, myopia, cataracts, glaucoma, thromboembollism, blusioin molting of skin, developmentatl delay, seizures
inheritance: auto rec
mutation: cystathione B synthatse (CSB) convertes homocysteine to serine/cystathionine -> inactive enzymes leass to increased methionine/homocysteine levels
**AA disorders |
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Term
| familial hypophosphatemic rickets |
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Definition
phenotype: bowing lower extermieties, waddling-gait, short, dolichocephaly (long head), tooth deformity
mutation: Xp22.2-p22.1, deficiency interference with Pi reabsorbance in kidney and converting 25-hydroxy-D to 1,25-hydroxy-2D
testing: hyperphosphaturia, normal AA, metaphysical widening/fraying, cupping of metaphysises at long bones
**transport disorder |
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Term
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Definition
phenotype: symptoms start with milk feeding, lethargy, hypoglycemia, seizures, more e. coli infections
inheritance: auto rec
mutation: galactose-1-P uridyltransferase (GALT) cconverts galactose-1-P to glucose-1-P -> this is mutated and results in accumulation of galactose-1-P
testing: newborn screening
treatment: eliminate lactose/galactose
**carohydrate metabolism disorder |
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Term
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Definition
phenotype: cerebella ataxia, emotional instability, delayed development, mental retardation, photosensitive skin
inheritance: auto rec
Mutation: SLC6A19 (mutation) on Chr. 5 -> neutral AA transport across brush border membrane of kidney
treatment: nicotinic acid for deficiency of this vitamin, high protein diet
**transport disorder |
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Term
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Definition
phenotype: blindness (progressive), severe myopia, mitral valve prolapse, micrgnathia, small tongue, cleft palate
mutation: COL2A1, CoL11A1/2 |
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Term
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Definition
phenotype: basement membrane disorder, rneal failure, ocular anomilies
inheritance: auto rec(?)
mutation: COL4A5) on Xq22 |
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Term
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Definition
Phenotype: progressive ataxia,, muscle weakness, dysarthria, scoliosis, hypertrophic cardiomyopathy
**trinucleotide repeat disease |
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Term
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Definition
phenotype: kinky hair syndrome, hypothermia, hypotonia, myoclinc seizures, severe mental retardation, optic atrophy, osteopenia with pathologic fractures (child abuse)
inheritance: x-linked recessive
mutation: mutation in copper transporting ATPase, ATP7a, low serum copper and ceruloplasm levels
**MD |
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Term
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Definition
phenotype: "kayser-Fleischer" rings, renal tubular acidosis, involuntary movement, hemolysis
inheritance: auto rec
mutation: ATP7B, copper binding ATPase (specificially in liver copper accumulates and not excreted in bile), reduced serum copper/ceruloplasmin (but elevated copper in liver)
treatment: zinc acetate to stop copper absorption, penicillamin/trientine/tetrahiomolybdeate to up urine copper
**MD |
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Term
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Definition
| phenotype: hereditary breast cancer -> multi step carcinogenesis |
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Term
| familial adenomatous polyposis |
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Definition
phenotype: thousands of adenomatous polyps
inheritance: auto dom
mutation: APC gene (tumor suppressor)
Gardner syndrome = FAP + skull osteomas + soft tissue tumors |
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Term
| hereditary neurophathy with liability to pressure palsies |
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Definition
phenotype: foot drop/carpal tunnel, sensory dysfunction, pes cavus (arch foot)
mutation: deleted PM22 gene
testing: nerve biopsy shows sausage swelling of myelin sheath
**gene dose effect |
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Term
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Definition
phenotype: brachycephaly (from craniosynostosis), midface hypoplasia, hypertelorism, mitten hand, mental retardation, coronal suture fuses early = "tower skull"
inheritance: auto dom
mutation: FGFR-2 (gain of function)
**gain of function" |
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Term
| hereditary hemachromatosis |
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Definition
| phenotype: liver damage/cirrhosis, hepatoma, diabetes mellits, cardiomyophathy, skin-hyperpigment (bronzing) inheritance: auto rec mutation: mutation in HFE gene, interfering with hepcidin's ability (hormone synthesized by liver) to impede iron absorption = iron overload testing: high serum ferritin **MD, sex difference in penetrance (women -> period |
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Term
| chronic myelogenous leukemia |
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Definition
inheritance: BCR-ABL "fusioin protein"
-somatic mutation
-gleevec (imatanib mesylate)
-philadelphia chromosome/translocation?? |
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Term
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Definition
phenotype: mucus build up, infection, Jews, salty baby
inheritance: auto rec
mutation: mutation in CF transmembrane conductance regulator chlorine channel (CFTR) |
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Term
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Definition
•Inflammatory bowel disease
–Other type of inflammatory bowel disease is ulcerative colitis which only affects colon and has high risk of colon cancer development
–Abdominal pain and diarrhea; transmural ulceration and granulomatous inflammation; fistulas
–Autoimmune disease
•Variants of NOD2 gene
–NOD2 protein binds to Gram-negative bacterial cell walls and activates monocyte NF-κB transcription factor
•Multifactorial inheritance
•Ethnic predilection – Ashkenzi Jewish |
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