Genetic Disorders and Inborn Errors of Metabolism Flashcards
number of specific number nucleotide copies within a gene increases
unstable repeat sequences
Both members of a chromosome or gene pair are inherited from same parent
Uniparental disomy
translocation
transfer of chromosomal material from one chromosome to another
Genomic imprinting
gene defect is expressed solely based on the sex of the parent
Angleman Syndrome
mothers abnormal 11q region on chromosome 15
Prader-willi
Fathers abnormal 11q region on chromosome 15
Intrinsically abnormal process forms abnormal tissue
malformation
Mechanical forces exerted on normal tissue result in abnormal tissue
Deformation
normal tissue becomes abnormal after being subjected to destructive forces
Disruption
Syndrome
collection of seemingly unrelated abnormal features occur in a familiar pattern
Triple marker for down syndrome
- low AFP
- low unconjugated estriol
- high Beta-HCG
triple marker for trisomy 18
low: AFP, unconjugated estriol, Beta-HCG
when can you do Chorionic villus sampling
10-13 weeks
when can you collect amniocentesis
16-18 weeks
what chromosome is Marfan found on? protein defect? inheritance?
15: fibrillin
Autosomal dominant
Clinical features of Marfan
- tall stature with elongated extremities and long fingers
- decreased upper to lower segment ratio
- upward lens subluxation
- aortic root dilation ( sudden death)
how is Marfan diagnosed
clinical however similar to homocystinuria
what increases the risk of aortic dissection and decreases risk
- hypertension and chest trauma
- beta-blocker and avoid contact sports
Clinical features of Prader-Willi
- Almond-shaped eyes
- fishlike mouth
- FTT first year, hyperphagia later in childhood
- short
- hypogonadism
- hypotonia
- mental retardation
diagnosis for Prader-willi and Angleman
FISH
childhood complication of Prader willi
obstructive sleep apnea
adulthood complication of Prader-Willi
- cardiac disease
- type 2 diabetes mellitus
“happy puppet” syndrome
Angelman syndrome
clinical features of Angelman syndrome
- jerky arm movements
- ataxia
- paroxysms of inappropriate laughter
- mental retardation ( severe)
Chromosome impacted in Noonan syndrome
chromosome 12
clinical features for Noonan
- short stature
- shield chest
- short webbed neck
- low hairline
- right sided heart lesions ( pulmonary valve stenosis)
CATCH-22
DiGeroge syndrome and Velocardiofacial syndrome
- Cardiac anomaly
- Abnormal facies
- thymic hypoplasia
- cleft palate
- hypocalcemia
complications of DiGeroge
- seizures due to hypocalcemia
- infections
Ehlers-Danlos syndrome? inheritance
- defective type V collagen
- autosomal dominant
Hyper extendable joints, fragile skin, tissue paper-thin scars, mitral valve prolapse
Ehlers-Danlos syndrome
Osteogenesis imperfecta
production of abnormal type 1 collagen
clinical features of osteogenesis imperfecta
- blue sclerae
- fragile bones
- yellow or gray-blue teeth
- easy bruisability
complications for osteogenesis imperfecta
- early conductive hearing loss and skeletal deformaties
VACTERL (VATER) association
- Vertebral defects
- Anal atresia
- Cardiac anomalies
- TE tracheoesophageal fistula
- Renal
- Limb defects
CHARGE association
- Colobomas
- Atresia of nasal choanae
- retardation
- Genital anomalies
- Ear anomalies
Colobams
absence or defect of ocular tissue
“cocktail party” personality ? chromosome?
Williams syndrome
- deletion on chromosome 7
Clinical features of Williams syndrome
- Elfin facies
- Mental retardation and loquacious personality
- Supravalvular aortic stenosis
- Idiopathic hypercalcemia
- connective tissue abnormalities
Elfin facies
- short palpebral fissures
- flat nasal bridge
- round cheeks
- Small for gestational age and FTT
- single eyebrow (synophrys)
- microcephaly
- infantile hypertonia
- mental retardation
- small hands and feet
- cardiac defects
- behavioral
Cornelia de Lange (Brachmann-de Lange)
Short stature, skeletal asymmetry and normal head circumference
Russell-Silver Syndrome
Clinical features of Russell-Silver syndrome
- small for gestational age
- small triangular face
- Cafe-au-lait spots
- excessive sweating
Clinical feature of Pierre Robin syndrome
- micrognathia
- cleft lip and palate
Complications for Pierre Robin syndrome
- recurrent Otits Media
- Upper airway obstruction
Partial deletion of short arm of chromosome 5 ? clinical feature?
Cri du chat syndrome
- cat cry
Second most common trisomy syndrome ? more common gender?
Trisomy 18
- female
Clinical features of Trisomy 18
- scissoring of lower extremities
- delicate, small facial features
- clenched hands with overlapping digits
- rocker bottom feet
clinical features of trisomy 13
- holoprosencephaly
- severe mental retardation
- microphthalmia
- cleft lip and palate
cardiac defect and limb defect in turner
- Left sided : coarctation of aorta
- swelling of dorsum of hands and feet
Most common inherited cause of mental retardation? defect?
Fragile X syndrome - CGG repeats
- mild to severe retardation, large eas, large testes
Fragile X syndrome
Most common cause of male hypogonadism and infertility ? genotype?
Klinefelter syndrome
- XXY
Proximal long bone abnormalities
Rhizomelia
Medial long bone abnormalities
Mesomelia
Distal abnormalities
Acromelia
Abnormalities of spine with or without limb abnormalities
Sondylodysplasias
Most common skeletal dysplasia
Achondroplasia
complications of achonroplasia
- foramen magnum stenosis –> hydrocephalus or cord compression
- obstructive sleep apnea
- orthopedic problems
clinical features of achondroplasia
- trident-shaped hands
- rhizomelic limb shortening
- lumbar kyphosis in infancy
- lumbar lordosis in later childhood
- recurrent otitis media with conductive hearing loss
cause of Potter syndrome
- severe oligohydramnios
Most common teratogen
fetal alcohol syndrome
Table 5-2
page 130
Most common congenital anomalies of central nervous system
Neural tube defect
Initial Laboratory evaluation for inborn error of metabolism
- metabolic acidosis
- elevated serum ammonia
what increases ammonia excretion
- Sodium benzoate
- sodium phenylacetate
Homocystinuria? inheritance
- Cystathionine synthase deficiency
- autosomal recessive
difference between Homocystinuria and Marfanoid body
- Marfanoid body habitus without arachnodactyly
- Homocystinuria downward lens subluxation
Clinical features of Homocystinuria
- hypercoaguable state
- Cardiovascular abnormalities
- scoliosis
- developmental delay
Diagnosis for Homocystinuria
Increased methionine
Management of Homocystinuria
- Methionine-restricted diet
- aspirin
Premature infants who receive high-protein diets
transient tyrosinemia of the newborn
Diagnosis for transient tyrosinemia of the newborn
-elevated serum tyrosine and phenylalanine levels
Management of transient tyrosinemia of the newborn
vitamin C
prognosis for transient tyrosinemia of the newborn
self-limited disease
what is cystinuria
defect in renal reabsorption of cystine, lysine, arginine, and ornithine that leads to renal stones
Hartnup disease
defect in transport of neutral amino acids
what are ammonia levels in urea cycle defect
elevated ammonia greater than 200 muM
how is transient hyperammoniemia of the newborn treated
self-limited
Most common urea cycle defect? inheritance
Ornithine transcarbamylase deficiency
- autosomal recessive
What should be suspected in any newborn with hepatomegaly and hypoglycemia
galactosemia
what is galactosemia
galactose-1-phosphate uridyltransferase deficiency
clinical features of galactosemia
- after feeding cow’s milk or breast milk
- hepatomeglay
- cataracts (oil drop appearance)
- renal tubular acidosis
diagnosis for galactosemia
nonglucose-reducing substance in urine
managment for galactosemia
galactose-free diet
Prognosis for galactosemia
- normal intelligence if disorder is treated early
- all females have ovarian failure
- E. coli sepsis death
What is hereditary fructose intolerance
- fructose-1-phosphate aldolase B deficiency
2 characteristics of glycogen storage
organomegaly and metabolic acidosis
glucose-6-phosphatase deficiency
Von Gierke’s disease
alpha- glucosidase deficiency
Pompe’s disease (GSD type 2)
Von Gierke’s disease have a high risk for what
hepatocellular carcinoma
Most common fatty acid oxidation disorder
Medium-chain acyl-CoA dehydrogenase
characteristics of fatty acid oxidation defect
- nonketotic hypoglycemia
- hyperammonemia
- myopathy
- cardiomyopathy
Common disease has atypical presentation or if disease involves 3 or more organ system
- mitochondiral disorder
- mitochondiral encephalopathy
- lactic acidosis
- strokelike episodes
MELAS
- ophthalmoplegia
- pigmentary degeneration
- degeneration of retina
- hearing loss
- heart block
- nuerolgic degeneration
Kearns-Sayre syndrmoe
how is diagnosis of mitochondrial disorder made
tissue biopsy revealing abnormal mitochondria
Tay Sachs? inheritance?
hexosaminidase A deficiency
- AR
infantile onset of tay sachs
- hyperacusis
- macrocephaly
- cherry red macula
- severe developmental delay
Juvenile or adult onset tay sachs
cherry red macula absent
prognosis for tay sachs
infantile: untreatable
juvenile: poor prognosis
Gaucher’s disease
glucocerebrosidease deficiency
what is the most common gangliosidosis
Gaucher’s disease
common feature for Gaucher’s disease
Erlenmeyer flask-shape to the distal femur
Niemann-Pick
sphingomyelinase deficiency
Metachromatic leukodystrophy caused by
arylsulfatase A deficiency
