IEM/Thermal Regulation Flashcards
Glycogen storage disease type I and II (enzymes)
Type I: glucose 6 phosphatase (Von Gierke)
Type II: lysosomal alpha-glucosidase (Pompe)
Most common urea cycle defect; inheritance
Ornitihine carbamyl transferase, X-linked recessive
Urea cycle clinical presentation; treatment
present in first few days of life with poor feeding, vomiting, apnea, and changes in mental status. Hyperammonemia, respiratory ALKALOSIS, normal serum glucose
Tx: remove infant’s nitrogen by limiting protein intake, administration of sodium benzoate or phenylacetate, or HD
Niemann-Pick syndrome
congenital lipidosis, lysosomal storage disease. Macular cherry red spots, clear corneas, FOAM cells on BM biopsy.
Sphingomyelinase defect
Inheritance of pyruvate dehydrogenase, clinical presentation
mitochondrial d/o
Developmental delay, poor muscle tone and weakness, seizures, ataxia, choreoathetosis, global cerebral atrophy
Absent CC, subtle facial dysmorphology. Narrow head with frontal bossing, wide nasal bridge, long philtrum, flared nostrils. Anion gap MA with elevate lactate and pyruvate levels
Next step when suspect tyrosinemia
send serum and urine succinylacetone levels and urine reducing substances
Phenylalanine –> Tyrosine –> dopamine slash phenylpyruvate fumarate + acetoacetate
Biotinidase deficiency (AR)
sx are result of decreased available biotin for enzymatic reactions.
IMMUNE dysfunction, alopecia, skin rash. NEURO dysfunction, seizures, hypotonia, lethargy, ataxia, blindness, hearing loss.
Tx oral biotin supplementation. Does NOT cause nystagmus
Menkes disease
X-linked recess; brittle, steely, kinky hair. Disrupts nervous system and bone development. Dx – low ceruloplasmin and copper levels
Non-ketotic hyperglycinemia
AR, defective cleavage of glycine eto ammonia
Hyperammonemia differential dx
- Acidosis and ketonuria
- Acidosis without ketonuria
- Absence of acidosis and ketonuria (Transient) – related to immaturity of N-acetylglutamate synthetase enzyme activity
Homocystinuria
Optho: DOWNward dislocated lens, glaucoma, myopia
Bones: osteoporosis, scoliosis, increased tendency to fracture, TALL, arachnodactyly, decreased joint mobility
Neuro: DD, cognitive impairment, seizures
Heme: increased thrombosis and bleeding
Treatment of Wilson’s disease
D-penicillamine (copper chelator)
Biotin function
binds to carboxylases, enhances function
Gaucher
Niemann Pick
Tay-Sach’s
N-acetylglutamate synthetase
Gaucher = Glucocerebrosidase – Gaucher cells in bone marrow
Niemann Pick = Sphingomyelinase – cherry red spots, FOAM CELLS in BM
Tay-sach’s – heosaminidase, cherry red spots, NORMAL BM
17A / D
N-acetylglutamate synthetase deficiency
Urea cycle disorder
N-acetylglutamate synthetase
Carbamyl phosphate synthetase [both have normal or low orotic acid]
Ornithine carbamyl transferase
Arginosuccinic acid synthetase
Arginosuccinic lyase
Arginase
Classic galactosemia
liver failure, hypoglycemia, LFTs up
NOT lactate elevated
Galactose-1 phosphate uridyl transferase (GALT) deficiency: Classic galactosemia, the most common and most severe form
Deficiency of galactose kinase (GALK)
Deficiency of galactose-6-phosphate epimerase (GALE)
Name diagnostic test
Galactosemia
D/o of AA metabolism
Organic acidemia
Fatty acid oxidation defects
Glycogen storage diseases
Galactosemia – urine non-glucose reducing
D/o of AA metabolism – abnormal serum AA
Organic acidemia – abnormal urine organic acids
Fatty acid oxidation defects – abnormal acylcarnitnie
Glycogen storage diseases – increased serum ketones and lactate
If sample not sent on ice, then ammonia will be _____
elevated
How to diagnose fatty acid oxidation disorder?
Acylcarnitine profile is more informative in diagnosing fatty oxidation defects than total and free carnitine concentrations
Organic acidemia features
metabolic acidosis and abnormal UOA
Pyruvate metabolism or mitochondrial energy metabolism defects
metabolic / lactic acidosis
Urea cycle defects lab test
Urea cycle defects: abnormal plasma amino acids
Type I vs Type II glycogen storage disease
Type I: Glucose -6 – phosphatase, liver/kidney/GI, LACTIC ACIDOSIS, HM, neutropenia, FTT, diarrhea. Bleeding disorder.
Type II Pompe = lyososomal alpha-glucosidase – affects all organs, symmetric severe muscle weakness, cardiomegaly, HOCM, CHF.
