Fructokinase

AR; benign, asymptomatic

Sx: fructose in blood and urine

*dietary fructose can still be metabolized via hexokinase (->Fructose-6-phosphate)

Aldolase B

AR

Fructose-1-P builds up -> ↓ avail. P -> inhibition of glycogenolysis and gluconeogenesis

Sx: hypoglycemia, jaundice, cirrhosis, vomiting

Tx: ↓ intake of both fructose and sucrose

Galactokinase

AR; mild condition

accum. of galactitol

Sx: galactose in blood and urine, cataracts

Ex: an infant that can't track objects or develop a social smile

*Aldose reductase is responsible for galactose conversion to galactitol

Galactose-1-P uridyltransferase

AR

accum. of toxic substances (incl. galactitol)

Sx: failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation

Tx: exclude galactose and lactose from diet

Alkaptonuria

(onchronosis)

Homogentisic acid oxidase

AR, benign

Sx: black urine, dark connective tissue, brown pigmented sclera; may have arthralgias (homogentisic acid is toxic to cartilage)

α-ketoacid dehydrogenase

blocked degradation of branched aa's (Ile, Leu, Val) → α-ketoacids accum. in blood, esp. Leu

Sx: severe CNS defects, mental retardation, and death

*urine smells like maple syrup

*"I Love Vermont maple syrup from branched maple trees"

defective neutral aa transporter on renal and intestinal epithelial cells

AR

tryptophan excretion in urine and decr. absorption from gut

*Leads to Pellagra (Niacin def) → 4 D's of Pellagra: diarrhea, dermatitis, dementia, and death

Type I glycogen storage dz

Glucose-6-P

Sx: severe fasting hypoglycemia, ↑↑ glycogen in liver, lactic acidosis, hepatomegaly

*No glycogenolysis or gluconeogenesis

Can see hyperlipidemia, hyperuricemia, and impaired fructose metab.

Type II glycogen storage dz

Lysosomal α-1,4-glucosidase (aka acid maltase)

Sx: Cardiomegaly

*inappropriate accum. of glycogen in heart, liver, and muscle

"Pompe's trashes the Pump"

Type III glycogen storage dz

α-1,6-glucosidase (aka debranching enzyme)

Sx: muscular hypotonia

-milder form of Von Gierke's (type I) w/ normal blood lactate levels

*glycogen accum. in liver and heart

*gluconeogenesis is intact

Type V glycogen storage dz

skeletal muscle glycogen phosphorylase

glycogen accum. in muscle, but can't break it down

Sx: painful muscle cramps/myalgias and myoglobinuria w/ exercise

AR def. of UDP-N-acetylglucosamine due to def. of N-acetylglucosaminyl-L-phosphotransferase

-loss of protein tagging w/ mannose-6-P → defective trafficking of enzymes into lysosomes (secreted outside of cell instead)

Sx: developmental delay and coarse facial features, clouded corneas, restricted joint movement

α-galactosidase A

X-linked recessive

accum. of ceramide trihexoside → peripheral neuropathy of hands/feet (acroparesthesia), angiokeratomas, cardiovascular dz, progressive renal failure

β-glucocerebrosidase

AR, MC Lysosomal storage dz

glucocerebroside accum. in brain, bone marrow, liver, and spleen → hepatosplenomegaly, aseptic necrosis of femur, bone crises

*Gaucher's cells: macrophages that look like "crumpled tissue paper"

(glucocerebroside accum. w/i phagocytes)

Sphingomyelinase

AR

-accum. of sphingomyelin (w/i phagocytes) → progressive neurodegeneration (spasticity, hypotonia), hepatosplenomegaly, cherry-red spot on macula, foam cells

*Death by age 3 typically

Ex: may present as a young child w/ loss of previously acquired motor capabilities

*"No Man Picks his nose w/ his Sphinger"

Hexosaminidase A

AR

-accum. of GM₂ ganglioside → prog. neurodegeneration, developmental delay, cherry-red spot on macula, lyosomes w/ onion skin

*NO hepatosplenomegaly (vs. Niemann-Pick)

*death usually before age 3

Galactocerebrosidase

(aka galactosylceramide β-galactosidase)

AR

accum. of galactocerebroside → peripheral neuropathy, developmental delay, optic atrophy, globoid cells

*death usually before age 3

Arylsulfatase A

AR

accum. of cerebroside sulfate → central and peripheral demyelination w/ ataxia and dementia

α-L-iduronidase

AR mucopolysaccharidosis

accum. of heparan sulfate & dermatan sulfate → developmental delay, gargoylism, airway obstruction, corneal clouding

Iduronate sulfatase

XR mucopolysaccharidoses

accum. of heparan sulfate & dermatan sulfate → a milder form of Hunter's, but w/ aggressive behavior and NO corneal clouding

*"aggressive Hunter's need to see the X clearly" (aggessive, X-linked, no corneal clouding)