Metabolic Disease in Kids

• d/o amino acid metabolism (AR)
• phenylalanine can't be converted to Tyr (becomes essential)

• Accumulate: phenylalanine & metabolites
• Deficiency: phenylalanine hydroxylase (rarely cofactor tetrahydrobiopterin)
• Distinct Features: fair hair/skin, blue eyes, mousy odor; MR

• d/o amino acid metabolism (AR)
• homocystein present in greater than trace amts in urine
• homocysteine not remethylated to methionine

• lethargy
• anorexia
• anemia
• rashes
• diarrhea

• Accumulation: homocystine, methionine
• Def: usually cystathionine synthase
• Features: ectopia lentis (subluxation of lens, signaled by iridodonesis - quivering of iris- & myopia); FTT & developmental delay

• Dx: usually made after 3 yrs of age by elevated methionine & homocysteine in body fluids
• Tx: high dose Vit B6, restrict methionine intake; betaine if unresponsive to B6 therapy

• leucine
• isoleucine
• valine

• d/o branched chain aa metabolism
• defect in decarboxylation of leu, iso, & val by branched chain ketoacid dehydrogenase

• Accumul: branched-chain aa's: Leu, Iso, Val
• Def: branched-chain ketoacid dehydrogenase
• Feature: odor of maple syrup in urine, sweat, cerumen

• poor feeding/vomiting 1st week of life
• alternating hypertonicity & flaccidity, convulsions, hypoglycemia
• odor of maple syrup in urine, sweat, cerumen

• Accumul: deficiency of neutral aa's: tryptophan
• Def: Na-dependent aa transport system in renal tubules & intestines
• Features: most asymptomatic

inherited defect in transport of neutral amino acids by intestinal mucosa & renal tubules b/c deficient activity of Na-dependent transport system

• most common lysosomal storage disease
• splenomegaly most common presenting sign
• def: beta-glucosidase
• accumul: glucocerebgroside
• pancytopenia; bone fx's, pain; 'crinkled paper' cytoplasm

• def: betagalactosidase
• accumul: GM1 ganglioside
• 50% cherry red spot on macula
• HSM
• rashes, edema, coarse facial features, skeletal abnorm
• blind & deaf by 1 yr, death by 3-4 yrs

• Tay-Sachs: deficiency alpha subunit hexoseaminidase A, accumul GM2 ganglioside in brain
• Sandhoff disease: accumul GM2 gnaglioside in brain & peripheral organs; defect beta subunit hexoseaminidases A + B
• Dx: 5-6 mos; death by 3-5 yrs
• cherry red spot on macula; hyperacusis; froglike position
• NO organomegaly in tay sachs; HSM in Sandhoff

• lysosomal storage disease
• def: sphingomyelinase
• accumul: sphingomyelin & cholesterol
• 50% cherry red spot on macula; HSM, neonatal jaundice
• dx by 4 mos, death by 3 yrs
• neuro signs/deterioration

• lysosomal storage disease
• def: ceramide trihexosidase or alpha-galactosidase A
• accumul: glycosphingolipids in vascul endothelium, nns, & organs
• angiokeratomas (dark, red, punctate macules don't blanch, clusters, b/l symmetric naval & buttocks); telenangiectasias
• 1ST SIGN: severe neuropathic limb pain
• asymmetric corneal deposits
• progressive kidney failure (bx w/ lipid)

• lysosomal storage disease
• def: galactosyl-ceramide beta-galactosidase or galactocerebrosidase
• accumul: ceramide galactose w/i lysosomes white matter
• progressive CNS degeneration/ sx w/i 1st 6 mos life
• optic atrophy, spasticity, early death
• globoid cells in areas of demyelination
• Stem cell transplant prior to onset neuro sx

• lysosomal storage disease
• def: ceramidase
• accumul: ceramide in periph organs, joints, LNs
• dx at 1 yr
• nodules (granulomas w/ ceramide) on joints, vocal cords (hoarse, resp complications)
• severe MR & motor retardation

• mucopolysaccharidoses - lysosomal storage
• normal at birth, dx at 1+yrs
• excess urinary excretion GAGs
• progressive mental & physical deterioration
• coarse features, corneal clouding, stiff joints
• organomegaly, skeletal abnormalities

• glycogen storage disease
• def: glucose-6-phosphatase
• S/Sx: fasting hypoglycemia, hepatomegaly, elevated serum lactate, uric acid, cholesterol, TGs; renal complications
• Dx: 5 mos; administer epi, glucagons, galactose, et doesn't provoke normal hyperglycemic response
• Tx: freq high carb meals

• glycogen storage disease
• deposit glycosgen in skeletal mm.
• S/Sx: weak/cramp skeletal mm during/after exercise; no rise blood lactate during ischemic exercise; '2nd wind' w/ initation FA metabolism
• Presents: adolescence/ early childhood; mm bx & assay
• myoglobinuria, elevated CK at rest
• Tx: sucrose prior to aerobic exercise

• glycogen storage disease
• Def: alpha-1,4-glucosidase; can't convert mannose-> glucose
• S/Sx: rapid progressive cardiomyopathy w/ cardiomegaly, macroglossia, hypotonia, hepatomegaly; death 1-2 yrs old
• Juvenile form = milder, slowly progressive to myopathy, no cardiac abnormality; death 2/2 resp failure
• Dx: ECG, EMG

• S/Sx: cataracts, HSM, MR, sepsis (e.coli)
• Dx: jaundice, hepatomegaly, vomiting, hypoglycemia, convulsions, lethargy, irritable, feeding difficulty, poor wt gain, diarrhea, aminoaciduria, hepatic cirrhosis, ascites, MR
• Tx: exclude galactose & lactose from diet

• def: fructokinase; elevated fructose & metabolite levels
• Asymptomatic till fructose introduced into diet; fructosemia & fructosuria

• X-linked recessive; defect purine metabolism
• def: HGPRT
• S/Sx: retardation of motor development, spastic cerebral palsy, self injurious behavior; hyperuricemia, uricosuria, uriary tract calculi, nephropathy, tophi, gouty arthritis
• Dx: dx ~3mos when delayed motor development apparent; serum uric acid levels