Metabolic Disorders Flashcards
Lesch-Nyhan Syndrome
-Absent HGPRT enzyme (normally converts hypoxanthine –> IMP and guanine –> GMP in purine salvage pathway)
H- hyperuricemia (orange sand in diaper from crystals)
G - gout
P - pissed off (aggression and self-mutilation)
R - retardation
T - tone (dystonia)
-X linked recessive
I Cell Disease
- Lysosomal storage disease (inclusion cell disease)
- Defect in N-acetylglucosaminyl-1-phosphotransferase so Golgi cannot phosphorlate mannose residues –> proteins secreted rather than delivered to lysosome
- Facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes
Zellweger Syndrome
- Problem w/ peroxisomes
- Hypotonia, seizures, hepatomegaly, early death
Refsum Disease
- Problem w/ peroxisomes
- Scaly skin, ataxia, cataracts/night blindness, short 4th toe, epiphysial dysplasia
Osteogenesis Imperfecta
- Auto dominant defect in collagen I synthesis
- COLIA1/COLIA2 genes
-cannot BITE
B- bones (multiple fractures)
I ("eye") - blue sclera
T - teeth (dental imperfections)
E - ear (hearing loss b/c abnormal ossicles)
Ehlers-Danlos Syndrome
-Faulty collagen synthesis (can be auto dominant or recessive)
- Classic Type - joint and skin manifestations; collagen V
- Vascular Type - vessel and organ rupture; collagen III
- Hyper-mobility Type - most common; joint instability
Menkes Disease
- Defective Menkes protein (ATP7A) –> impaired copper absorption and transport –> no co-factor for lysyl oxidase
- Brittle kinky hair, growth retardation, hypotonia
- X-linked recessive
Marfan Syndrome
- FBN1 gene mutation on chromosome 15
- Auto dominant
- Defective fibrillin (sheath around elastin) –> skeleton, heart, eye problems
- Tall w/ long extremities, pectus, hypermobile joints, arachnodactyly (long fingers and toes), aortic dissection/aneurysm, floppy mitral valve, subluxation of lens upward
Hartnup Disease
- Deficiency of neutral AA transporters in proximal renal tubule and enterocytes –> aminoaciduria and dec absorption from gut
- Dec tryptophan which is usually converted to niacin –> pellagra-like symptoms (Diarrhea, Dementia, Dermatitis of collar-bone)
- Auto recessive
Pyruvate Dehydrogenase Complex Deficiency
X-linked
- Causes buildup of pyruvate that then gets shunted to lactate (LDH) and alanine (ALT)
- Neuro deficits, lactic acidosis, inc serum alanine
- Tx - pureLy ketogenic AAs (Lysine and Leucine)
Essential Fructosuria
- Defect in fructokinase
- Inc fructose in blood and urine but generally asymptomatic b/c fructose not trapped in cell
- Auto recessive
Fructose Intolerance
- Deficiency of aldolase B
- Fructose-1-phos accumulates in cells which dec available phosphate –> inhibits gluconeogenesis and glycogenolysis
- Hypoglycemia, jaundice, cirrhosis, vomiting after consumption of fruits, juice, honey
- Dec intake of fructose and sucrose
- Auto recessive
Galactokinase Deficiency
- Galactitol accumulates when galactose in diet
- Causes inc galactose in blood and urine + cataracts in infants but relatively mild
- Auto recessive
Classic Galactosemia
- Absence of galactose-1-phosphate uridyltransferase –> accumulation of galactitol in eye and other places
- Jaundice, failure to thrive, hepatomegaly, infantile cataracts, intellectual disability
- Predisposed to E coli sepsis
- No galactose or lactose in diet
- Auto recessive
Ornithine Transcarbamylase Deficiency
- Urea cycle disorder (most common)
- X-linked recessive
- Dec ammonia elimination and excess carbomyl phosphate becomes orotic acid (pyrimidine synthesis)
- Inc orotic acid in blood and urine
- Dec BUN and hyperammonia symptoms
- No megaloblastic anemia (unlike orotic aciduria)
Adenosine Deaminase Deficiency
-Required for degradation of adenosine and deoxyadenosine so if deficient –> inc dATP (TOXIC to lymphocytes so major cause of auto recessive SCID)
Karteneger Syndrome
- Immotile cilia due to dyenin arm defect
- Immotile sperm, dysfunctional fallopian tube cilia (inc risk ectopic)
- Bronchiectasis, sinusitis, ear infections, conductive hearing loss
- Situs inversus
PKU
- Auto recessive
- Dec phenylalanine hydroxylase or BH4 cofactor –> cannot convert to tyrosine (now essential)
- Intellectual disability, body odor, fair skin, growth retardation, eczema
Maple Syrup Urine Disease
- Auto recessive
- Block degradation of branched AA (isoleucine, leucine, valine) - lack of branched DH –> inc alpha keto acids in blood
- Vomit, poor feeding, urine smells like syrup
I Love Vermont maple syrup (Iso Leu and Val) - maple trees have b1ranches - branched and supplement w/ thiamine (B1)
Alkaptonuria
- Auto recessive
- Def in enzyme for tyrosine –> fumarate degradation –> pigment-forming homogentisic acid (blue-black connective tissue - ear, sclera, urine when exposed to air)
Homocystinuria
MULT FORMS all auto recessive
- Cystathionine synthase def
- dec affinity of this enzyme for pyridoxal phos cofactor
- Methionine synthase def
Homocysteine can be converted to methionine by methionine synthase OR converted to cystathionine by cystathionine synthase
Either way get inc homocysteine –> in urine + osteoporosis, Marfan body, down and in lens, cardio, kyphosis
Cystinuria
Auto Recessive
- Defect in prox tubule so cannot reabsorb COLA (cystine ornithine, lysine, arginine)
- Can lead to cystine stones in urine
- Tx = alkalyze or chelate (penicillamine)
