Metabolic Flashcards
Fatty acid oxidation defects vs. Glycogen storage disease (Von Gierke Type I)
BOTH hypoglycemia and hepatomegaly.
Urine Ketones:
- none or low in FA oxidation
- high in glycogen storage disease
Presentation:
- FAO: usually precipitated by viral illness
- GSD: usually “prolonged fasting” or sleeping thru the night for the first time
B6 is used to treat what disorder?
Homocystinuria
- B6 enhances activity of the deficient enzyme (cystathionine beta-synthase)
Lesch Nyhan
Developmental delay, Decreased IQ Dystonic movements Hypotonia, Hyperreflexia Vomiting SELF-MUTILATION
X-linked
Deficiency of HGPRT
Increased Uric acid
-> renal stones and CKD
Smith-Lemli-Opitz Syndrome
Defect in cholesterol biosynthesis
Accumulation of toxic cholesterol precursors
Autosomal Recessive
SGA, lots of dysmorphic features with syndactyly of 2-3 toes, structural abnl of CNS, hypoplastic LH, GI and renal abnl.
Die by 18 months
Tyrosinemia Type I (Hepatorenal Tyrosinemia)
- FTT
- hepatic failure (hepatomegaly with hepatoblastoma and liver failure)
- renal tubular acidosis
- rickets
Dx: urine succinylacetone level is high
Tx: NTBC (blocks tyrosine metabolism before the block)
Menkes disease
KINKY HAIR
low iQ
collagen abnl
X-linked
Dysfunction of copper metabolism - low copper
MPS: Hurler vs. Hunter
Lysosomal Storage disorder
- deficiency of lysosomal enzymes required for the degradation of mucopolysaccharides or glycosaminoglycans, which then lead to abnormal accumulation of heparan sulfate, dermatan sulfate, or keratan sulfate. These metabolites then accumulate in the brain, cornea, bones, heart, lungs, liver, and spleen.
Hurler
- AR, defect in alpha-L-iduronidase
- coarsened facial features, large tongues
- corneal clouding
- Macrocephaly and communicating hydrocephalus
- low IQ
- skeletal growth retardation and dysostosis multiplex and joint stiffness
- atlantoaxial subluxation
- prognosis related to CARDIAC involvement
Hunter:
- X-linked, BOYS
- NO CORNEAL CLOUDING
- milder MPS1
Treatment of FAO defects
Hypoketotic hypoglycemia and Reye-like syndrome
Carbohydrates (IV Dex) + Carnitine (needed to move LCFA into the mitochondria)
What disease is associated with subdural hematomas and retinal hemorrhages?
Glutaric Acidemia
- defect in catabolic pathway of lysine, hydroxylysine, tryptophan
Essential amino acid substitution pairs
Phenylalanine by tyrosine
Methionine by cysteine
Adrenoleukodystrophy
Peroxisomal Disorder of FA degradation
-> accumulation of Very Long Chain FA***
leading to CNS demyelination
Associated cortisol deficiency/addison’s
- you get hyperpigmentation
X-linked
Developmental regression is a red flag for?
Inborn errors of metabolism associated with neurologic deterioration and intellectual disability
Sanfilippo syndrome = mucopolysaccharide disorder
- inability to degrade heparan sulfate
- progressive mental deterioration, coarse facial features, joint stiffness, mild hepatosplenomegaly
VS:
Newborn screening includes biotinidase def, maple syrup disease, phenylketonuria - all of which are treatable and present in early infancy.
Tay Sachs
Tay-Sachs disease is an autosomal recessive metabolic disorder caused by hexosaminidase A deficiency, which Presents as a neurodegenerative disorder. After an initial period of normal development in early infancy, there is loss of motor skills, increased weakness, decreased alertness, and increased startle response between 3 and 6 months of age.
Physical examination findings of Tay-Sachs disease include a cherry-red spot of the fovea centralis of the macula of the retina, normal-sized liver and spleen, hyperreflexia, ankle clonus, and diffuse muscular hypotonia.
Diagnosis of Tay-Sachs disease relies on the demonstration of low to absent levels of β-hexosaminidase A enzymatic activity in the white blood cells, with normal to high levels of the β-hexosaminidase B isoenzyme.
Familial Lipoprotein Lipase Deficiency
HyperTAG
Abd pain, Pancreatitis, HSM
Eruptive Cutaneous Xanthomata - crops of small yellow papules
Impaired chylomicron clearance -> TAG accumulation
TX: Restrict fat intake
