Genetics Flashcards
Urine odor: sweaty feet, acrid
Glutaric acidemia type III, isovaleric acidemia
Urine odor: swimming pool
Hawkinsinuria
Urine odor: cat urine
3-hydroxy-3-methylglutaric aciduria
Urine odor: Boiled cabbage
Hypermethioninemia
Urine odor: tomcat urine
multiple carboxylase deficiency
Urine odor: Hops-like
Oasthouse urine diseaes
Urine odor: mousy or musty
Phenylketonuria
Urine odor: rotting fish
Trimethylaminuria
Urine odor: boiled cabbage, rancid butter
Tyrosinemia
Classic phenylketonuria
enzyme deficiency __
phenylalanine level __
Classic PKU
enzyme deficiency: phenylalanine hydroxylase
phenylalanine level: >20 mg/dL
Deficiency of fumarylacetoacetate hydrolase
Elevated succinylacetone
Presents between 2 and 6 mo
Acute hepatic crisis heralds onset
Acute peripheral neuropathy: severe pain in the legs, extensor hypertonia of the neck and trunk, vomiting, paralytic ileus, self-induced injuries, lasting 1-7 days
Fanconi-like syndrome
Treatment of choice is nitisinone
Tyrosinemia Type I (Tyrosinosis, Hereditary Tyrosinemia, Hepatorenal Tyrosinemia)
Deficiency of tyrosine aminotransferase
Hypertyrosinemia (20-50 mg/dL)
Palmar and plantar hyperkeratosis, herpetiform corneal ulcers, intellectual disability, ocular manifestations (tearing, redness, pain, photophobia), skin lesions (painful hyperkeratotic plaques)
Tyrosinemia Type II (Richner-Hanhart syndrome, Oculocutaneous Tyrosinemia)
Developmental delay, seizures, intermittent ataxia, self-destructive behavior.
No liver or renal abnormalities
4-hydroxyphenulpyruvic acid and metabolites in the urine
Tyrosinemia Type III (Primary deficiency of 4-HPPD)
Deficiency of homogentisic acid oxidase
Ochronosis (dark spots on the sclera or ear cartilage), arthritis, blackening of urine on standing
Treatment: nitisinone, phenylalanine- and tyrosine-restricted diet
Alkaptonuria
Lipidosis
B galactosidase deficiency
hepatosplenomegaly, angiokeratoma, developmental delay, macular cherry-red spot
Facies: low-set ears, frontal bossing, depressed nasal bridge, long philtrum
Death usually occur by 3-4 yr
GM1 Gangliosidosis
B-hexosaminidase deficiency
loss of motor skills, mental deteriorationincreased startle reaction, macular pallor, retinal cherry-red spots, hyperacusis, macrocephaly
GM2 Gangliosidosis
Tay-Sachs disease, Sandhoff disease
Acid B-glucosidase deficiency/glucocerebrosidase
hematologic abnormalities, organomegaly, skeletal involvement, bone pain,
Pathologic hallmark: wrinkled paper appearance
ERT
Gaucher
Acid sphingomyelinase deficiency
Hepatosplenomegaly, psychomotor retardation, neurodevelopmental regression,
Niemann-Pick
a-galactosidase deficiency
angiokeratoma ("bathing trunk areas"), hypohidrosis, corneal and lenticular opacities, acroparesthesias, vascular disease of the kidney, heart, brain
Pain is the most debilitating symptom
"Maltese crosses" in urinary sediment
ERTFabry disease
Galactocerebrosidase deficiency
Spasticity, cognitive impairment, optic atrophy,
Treatment: umbilical cord blood transplantation
Krabbe disease
Ceramidase deficiency
Painful joint swelling and nodule formation
Farber disease
Glucose-6-phosphatase deficiency
Growth retardation, hepatomegaly, hypoglycemia, doll-like facies
Biochemical hallmarks: hypoglycema, lactic acidosis, hyperuricemia and hyperlipidemia
GSD Type I: Von Gierke Disease
Acid maltase deficiency
Myopathy, cardiomyopathy, respiratory insufficiency
ERT
GSD Type II: Pompe Disease
Myophosphorylase defiency
Exercise intolerance, muscle cramps
GSD Type V: McArdle
Branching enzyme deficiency
Failure to thrive, hypotonia, hepatomegaly, splenomegaly, cirrhosis
GSD Type IV: Andersen
Debrancher enzyme deficiency
Hepatomegaly, growth retardation, muscle weakness, hypoglycemia
GSD Type IIIa: Cori or Forbes
Patients with galactosemia are at increased risk for which infection
E. coli neonatal sepsis
Iduronate 2-sulfatase deficiency
X-linked recessive
Clear cornea
Hunter
Behavioral problems, sleeping disorder, aggression, progressive dementia, clear cornea
Sanfilippo
Hyperuricemia, intellectual disability, dystonic movement disorder, arthric speech, compulsive self-biting
Lesch-Nyhan disease
HPRT deficiency
Most common genetic cause of moderate intellectual disability
Trisomy 21
Cleft lip often midline; flexed fingers with polydactyly; ocular hypotelorism; holoprosencephaly, hypoplastic or absent ribs
Median survival of 7 days; 91% die by 1 year
Trisomy 13 (Patau syndrome)
Low birthweight, closed fists with index finger overlapping the 3rd digit and the 5th digit overlapping the 4th, rocker-bottom feet
Trisomy 18 (Edwards syndrome)
