Pediatrics Genetic Disease

eesohbel's version from 2015-12-09 19:22

Lysosomal Storage Diseases

Question Answer
what is the disease angiokeratomas, telangiectasias, cardiac and renal involvement and painful neuropathy, corneal opacitiesFabry
what is enzyme deficiency in Fabryalpha galactosidase
first sign of Fabry's diseasesevere neuropathic limb pain
mode of inheritance of Fabryx-linked recessive
Krabbeprogressive CNS degeneration
what is the disease macrophages that look like crumpled tissue paper, hepatosplenomegaly, pancytopenia, severe bone and joint painGaucher disease
deficiency of glucocerebrosidaseGaucher
what is the disease hepatosplenomegaly, cherry red spot in maculaNiemann Pick
what enzyme is messed up in Niemann Picksphingomyelinase
what is the disease cherry red spot in macula, no hepatosplenomegalyTay Sachs
what enzyme is messed up in Tay Sachsb-hexosaminidase
what metabolite goes up in Tay SachsGM2 ganglioside
What enzyme is messed up in Gaucherb-glucocerebroside
demyelination leads to progressive ataxia and dementiametachromic leukodystrophy
corneal clouding, mental retardation and gargoylismHurler's
deficiency in Hurlersalpha L iduronidase
deficiency in Huntersiduronate sulfatase
a milder form of Hurlers with no corneal cloudingHunter's

HY genetic diseases

Question Answer
Down syndrome associated with an increased risk ofALL, hypothyrodisim, early onset Alzheimer's
rocker bottom feet, micrognathia, clenched hands, microcephalyEdwards
life span in Edwards1 year
trisomy 18Edwards
holoprosencephaly, cleft lip, microcephalyPatau
trisomy 13Patau
testicular atrophy, tall stature, gynecomastia and female hair distributionKlinefelters
mutations on chromosome 7CF
treatment for CFpancreatic enzymes and fat soluble vitamins (ADEK)
lymphedema of the hands and feet in the neonatal periodTurner
fair hair and skin, eczema, blond hair, blue eyes and a musty urine odorPKU
how to modify diet in PKUdecrease phenyalanine (artificial sweeteners), and increasing tyrosine


Question Answer
macrosomia, macroglossia, pancreatic beta cell hyperplasia leading to hypoglycemiaBeckwith-Wiedemann
management of Beckwith-Weidemanobtain ultrasound and serum AFP every 6 months through six years to look for Wilms nad hepatoblastoma
Prader Willipaternal chromosome
binge eatingPrader Willi
fetal valproate syndromecardiac defects, midface hypoplasia, meningomyocelce
isoretiononCNS malformations
VACTERLvertebral defects, anal atresia, cardiac defects, TE fistual esophageal atresia, esophageal atresia, renal defects, limb defects
CHARGEcoloboma, heart defects, atresia choaena, retardation, genital hypoplasia, ear anomalies

Hereditary Defects in Sugar Metabolism

EnzymeDefectClinical Presentation
Galactokinase deficiencyincrease in galactose and galacitolthe galacitol causes cataracts
Classic Galactosemiadeficiency in galactose-1-phosphate uridyltransferase leading to an increase in galactose 1-phosphate (very toxic). galactose (blood, urine), and galacitol (sugar alcohol)failure to trhive, jaundice, hepatomegaly, infantile cataracts, intellectual disability. Remove galactose and lactose from diet.
Essential Fructosuriadeficiency of fructokinasebenign condition marked by fructosuria
Hereditary fructose intolerancedeficiency of aldolase B also known as fructose-1-phosphate aldolase, increase in fructose and fructose-1-phosphateSymptoms present following consumption of fruit, juice or honey. Hypoglycemia, jaundice, cirrhosis, vomitting. toxic liver damage, renal disease. Remove fructose and sucrose from diet
Enzyme that takes care of some of the dietary fructose load in Essential fructosuriahexokinaseconverts the fructose to fructose 6-P so it can enter glycolysis


Question Answer
cataractsgalactokinase deficiency
failure to thrive, jaundice, cataracts, intellectual disabilitydeficiency in galactose-1-phosphate uridyltransferase
benign condictiondeficiency of fructokinase
symptoms present following fruit juicedeficiency of aldolase B also known as fructose-1-phosphate aldolase
How is galactose converted to galactitol that causes cataractsaldose reductase
benign conditiondeficiency of fructokinase

Glycogen Storage Diseases (all autosomal recessive)

DiseaseaEnzymeClinical Presentation
Von Gierke (I)glucose 6-phosphatase (liver and kidney)Liver cannot release stored glucose (increased glycogen in liver) leads to hepatomegaly. severe hypoglycemia. Body must rely on fat/protein for energy hyperlipidemia, lactic acidosis, hyperuricemia. Hepatic steatosis is a cardinal sign!
Pompe (II)alpha-1,4-glucosidase (lysosomes)Buildup of glycogen in cardiac muscles. Electron dense granules inside lysosomes. Restrictive cardiomyopathy is typical cause of death by age 2.
Cori (III)debranching enzyme 1,6 glucosidase in muscle and liverLiver cannot break down glycogen past a branch point. Milder form of Von Gierke. Muscle weakness and hypotonia help to distinguish from Von Gierke. Another key distinguishing feature is cytosolic accumulation of glycogen with abnormally short outer chains
McArdle's (V)muscle glycogen phosphorylasemuscle cramping, fatigue and myoglobinura with strenous exercise can lead to rhabdo. (Liver's version is called Hers)

Glycogen storage

Question Answer
what enzyme is messed up myoglobinuriamuscle glycogen phosphorylase. McArdles
what enzyme is messed up liver cannot break down glycogen past a certain branch pointdebranching enzyme. Cori
what enzyme is messed up buildup of glycogen in cardiac musclesalpha 1, 4 glucosidase. Pome
what enzyme is messed up liver cannot released stored glucoseglucose-6-phosphatase. Von Gierke
hypoglycemia after prolonged fasting and low ketone bodiesacyl CoA dehydrogenase

Amino acid deficiencies

DiseaseEnzymeClinical PresentationTreatment
PKUphenyalanine hydroxylase and tetrahydrobiopterin (malignant PKU)musty smelldecrease phenylalanine increase tyrosine
alkaptonuriahomogenestic acid oxidase, increased homonogestic acid dark urine
albinismtyrosinaseincreased risk of skin cancer
homocystinuriacystathionine synthase B6llens dislocation downward. looks like Marfan, in marfan lens goes up. :: homocysteine and methionine are elevated. this is thrombotic decrease intake of both. give B6, restrict methionine. give cysteine.
cystinuriano reabsorption of COLA (cysteine, Ornithine, Lysine and Arginine) cystine stonesurinary alkalinization, citrate, good hydration
maple syrup urine diseasealpha ketoacid dehydrogenase (blocked degradation of branched amino acids, valine, isoleucine, leucine) requires thiaminesweet smelling urinedecrease isoleucine, leucine and valine. give thiamine.
Hartnupdecreased tryptophanniacin deficiency leads to pellagra
OTC deficiencyornithine transcarbamylase deficiencyincreased orotic acid in blood and urine, symptoms of hyperammoniemia. No megaloblastic anemia vs (orotic aciduria)decrease protein consumption. treatment for hyperammoniemia
orotic aciduraUMP synthase deficiencyincreased orotic acid, no symptoms of hyperammoniemia. Megaloblastic anemia (does not improve with B12 or folate)

Amino Acid deficiencies Memorizable Version

Question Answer
deficiencies in PKUphenylalanine hydroxylase or tetrahydrobiopeterin
treatment PKUdecrease phenylalanine increase tyrosine
alkaptonuria clinicaldark urine
enzyme messed up in alkaptonuriahomogenistic acid oxidase
clinical manifestation of homocystinurialens dislocation. looks like marfans, but lens goes down in homo. Increase homocysteine and methionine.
enzyme messed up in homocystinuriacystathionine synthase B6
cystinuriano reabsorption of COLA
Maple Syrup Urine disease enzymealpha ketoacid dehydrogenase
what are the branched amino acidsvaline, isoleucine and leucine
Hartnupdecreased tryptophan. leads to pellagra
difference between OTC deficiency and orotic aciduriaboth orotic acid in urine. Orotic aciduria has megaloblastic anemia. OTC deficiency has hyperammoniemia