Metabolic Disorders Flashcards
what happens when the transporter associated with carnitine uptake decificency isnt working?
carnitine gets wasted in the urine, low plasma levels
what makes up Friedrich ataxia?
hypoactive or absent DTRs, ataxia, corticospinal tract dysfunction, impaired vibratory function, HOCM, DM
what other metabolic disorder can be seen with methylmalonic acidemia?
homocystinuria (if has the enzyme deficit that blocks synthesis of methyl-B12)
how does CPT 2 present
exercise induced muscle pain and rhabdomyolysis
how does propronic acidemia present?
severe ketoacidosis +/- elevated ammonia, encephalopathy, vomiting, bone marrow suppresion, cardiomyopathy
organic acidemias can have what in common?
pancreatitis and bone marrow suppression
what physical findings occur in type 2 GSD?
infantile - cardiomegaly, hypotonia, death before age 1. juvenile - slowly progressive muscle involvement, no heart issues
what are children with galactosemia at risk for?
e. coli sepsis
what will be elevated in ornithine transcarbamoylase deficiency (OTC)
orotic acid levels
which type of MPS has predominately neurologic manifestations?
type 3, sanfilippo syndrome, inability to catabolize heparin sulfate
how is type 2 GSD (Pompe disease) different from other GSDs?
not an energy problem - it is a problem with accumulation of glycogen in lysosomes
what syndrome consists of ptosis, opthalmoplegia, and ragged-red fiber myopathy?
kearns-sayre syndrome (mitochondrial disorder)
how to diagnose acute intermittent prophyria?
measure hydroxymethylbiline synthetase in RBCs and look for abnormal porphobilinogen in the stool
if thinking that an amino acid disorder is present, what should you test?
urine organic acids and plasma amnio acids
how can you treat acute intermittent prophyria?
IV heme, IV glucose, narcotics,
what lab findings should make you think of type 1 GSD?
hyperlipidemia, elevated uric acid, hypoglycemia, elevated lactate
what are the two common hepatic porphyrias and how do they generally present?
acute intermittent porphyria, porphyria cutanea tarda —- neuropathy, mental disturbances, and abdominal pain
what is the enzyme defect in galactosemia?
deficiency of galactose 1-phosphate uridyltrasnferase — galactose will build up in liver, brain and kidney
what may come up in the history of a baby with nonketotic hyperglyceminia
in utero hiccups (and intractable seizures as a neonate)
what can cause clumsiness, intention tremor, dysarthria, proximal muscle weakness, and fasiculations?
juvenile tay-sachs
how does galactosemia present?
jaundice, HSM, hypoglycemia, irritability, cataracts, MR, vitreous hemorrhages, ascites, vomiting, seizures
what syndrome looks like hurlers but has hyperplastic gums?
mucolipidosis type II (I-cell deficiency)
when will type 1 GSD typically present?
age 3-4 months when babies start to space out feeds more and sleep through the night (more periods of fasting)
what will you see on muscle biopsy in type 2 GSD?
vacuoles filled with glycogen
what do you treat glutaric acidemia type 1 with?
L-carnitine, riboflavin, special diet
lab findings in type 5 GSD?
high CPK after exercise, elevated ammonia after exercise, normal lactate after exercise (muscle cells unable to use glucose effectively)
what is the defect in smith-lemli-optiz?
defect in cholesterol biosynthesis
what clues will you see with urea cycle defect?
resp alkalosis, low arginine, low BUN, high ammonia with relative normal liver function
what can cause achilles xanthomas?
familial hypercholesteroemia (AD transmission)
lemli-smith-optiz
what population is tay sachs more common in?
ashkenazi jews (also gaucher type 1)
how do patients with porphyria cutanea tarda present?
photosensitvity with bullae and vesicle eruption, milia, hypertrichosis and hyperpigmentation
how do you treat MCAD?
IV glucose and bicarb, avoid fasting,
what causes gaucher type 1?
deficiency of lysosomal glucocerebrosidase
how do you test for hyperglycinemia?
compare CSF to serum glycine levels
what is the only sphingolipidoses transmitted in X-linked fashion?
Fabry disease
how does Fabry disease present?
bone pain in hands and feet in adolescent boys, heat exposure and physical exertion will set off pain crises, patient will not sweat
what happens if you give glucagon or epinephrine to someone with type 1 GSD?
nothing, no rise in blood sugar
symptoms of hunters (MPS 2)
coarse facial features, learning difficulties, HSM, joint stiffness, *Nodular rash around scapula and extensor surfaces*
all amino acid disorders are inherited how?
AR
how do you treat fatty oxidation disorders?
l-carnitine
what is the deficiency in alkaptonuria?
homogentistic dixoygenase
what is the common presentation of pku
mousy/musty odor, vomiting, irritability, eczematoid rash, fair-haired, fair-skinned
all urea cycle disorders except which one are AR?
OTC deficiency (x-linked)
what type of lens dislocation is seen with homocystinuria?
lenticular subluxation that is downward and medial (marfan’s is upward) — (think downward/low IQ and upward/normal IQ)
how is Friedrich’s ataxia inherited?
AR
what are kids at risk for with Hurlers?
atlantoaxial subluxations, corneal clouding
what should you think of when you see “odor of sweaty feet”?
isovaleric acidemia
how does type 5 GSD (McArdle’s) present?
muscle cramps related to exercise, usually in adults,
which metabolic disease can cause subdural hematomas and retinal hemorrhages?
glutaric aciduria type 1 (autosomal recessive)
what do all forms of gaucher disease have in common?
HSM, bone involvement, lung involvement
what types of neurologic involvement do kids with type 3 MPS have?
devel delay, severe and challenging behaviors and aggression, hyperactivity
where does fatty oxidation occur?
mitochondria - so think of that when thinking of symptoms (hepatic, skeletal, muscular, cardiac)
what is the deficiency in MPS type 4?
galactose-6-sulfatase, can’t degrade keratin sulfate
what blood gas finding is suggested of an urea cycle defect?
respiratory alkalosis! (not a metabolic acidosis that you would see with sepsis)
what lab findings are present with maple syrup urine disease?
high leucine, isoleucine and valine in plasma and urine (also will see alloisoleucine)
menkes
Hurler syndrome
what urine abnormality is suggestive of alkaptonuria?
urine will look normal but then turn dark brown/black after being oxidized in the air
what syndrome consists of coarse facial features, mid-face hypoplasia, skeletal abnormalities, umbilical/inguinal hernias, macrocephaly?
Hurler syndrome (mucopolysaccharidosis type 1) - will also see liver and cardiac disease
how is smith-limli-optiz syndrome inherited?
AR
what do you need to consider adding to children with high phenylalanine levels who do not respond to dietary changes?
biopterin - may be part of that subset - will have neurologic progression
what treatment is available for gaucher?
enzyme replacement - doesnt help neuro deficits
what builds up in spingolipidoses?
ceramide (lipophilic core of sphingolipids)
how is PKU inherited
autosomal recessive
how are most carbohydrate metabolism disorders inherited?
AR
how is hunter’s inherited
x-linked, will only see in males,
lab findings for type 2 GSD?
high CPK, AST, and LDH.
what are people with homocystinuria at increased risk for?
thromboembolism
how does infantile tay-sachs present?
within first few months of life - axial hypotonia, extremity hypertonia, hyperreflexia, 90% have cherry red spot - auditory stimuli can cause seizures first signs are - enhanced startle reflex that does not diminish with repeated stimuli (unlike the moro)
what are examples of sphingolipidoses?
gaucher, neimann pick, fabry, tay-sachs
what is the most common form of inheritance for fatty oxidation disorders?
AR
what do you see in someone with MPS type 4 (morquio syndrome)
short-trunk dwarfism, skeletal dysplasia, odontoid dysplasia, normal intelligence, corneal deposits
how does MCAD present?
fasting induced lethargy and hypoglycemia, seizures, coma — elevated LFTs and CPK, low glucose
what are findings in adrenoleukodystrophy?
Developmental regression, progressive leukodystrophy; later onset with demyelination or Addison disease
Hunter Sydrome
how to diagnose MCAD?
elevated C8-C10
what ammonia levels will cause lethargy, brain edema, vomiting, and confusion
100-200
what medications can commonly trigger acute intermittent porphyria?
phenobarb, sulfonamides, anti-seizure meds, griseofulvin, OCPs
what is the defect in type 1 glycogen storage disease (von Gierke)?
glucose-6-phosphatase deficiency
Zellweger syndrome Hepatomegaly, profound hypotonia, Down syndrome–like facies, liver dysfunction
what porphyria looks like angioedema after sun exposure?
erythropoietic protoporphyria - will have redness, burning, itching after sun exposure, will have elevated levels of protoporphyrin
what is the underlying defect in neimann pick type C?
problems with routing of cholesterol esters through the lysosome
what are the two main differences between hunters and hurlers?
hunters - x-linked and no corneal clouding!
what is the typical presentation of NPD type C
axtaxia and hepatosplenomegaly at age 3-5, organomegaly, cataplexy and narcolepsy are common,
what is the treatment for type 5 GSD?
glucose before exercise
what causes tay-sachs?
B-hexsaminidase a-subunit deficiency
what disorder consists of epilepsy, cerebellar ataxia, and ragged-red fiber myopathy?
MERRF (myoclonic epilepsy and ragged-red fiber disease)
how is gaucher type 1 different from types 2 and 3?
only one with no CNS involvement
what other symptoms do people with MELAS have?
cardiomyopathy, diabetes, myopathy, ataxia
how can you treat porphyria cutanea tarda?
phlebotomy, hydxroychloroquine
what is a complication of LCHAD that is not present in VLCAD or MCAD
retinopathy and cholestatic liver disease
what is the defect with type 2 GSD?
acid a-1,4-glucosidase deficiency
how do chidlren with methylmalonic acidemia present?
high ammonia levels, thrombocytopenia, ketoacidosis (late: vomiting, hyperglycinemia, vomiting, FTT) can lead to renal failure, cardiomyopathy
what exam findings are prominent on gaucher type 1?
splenomegaly, pale, bone pain
what should you think of in a young person with a stroke?
MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes)
how does type 1 GSD present?
seizures, hypoglycemia, hepatomegaly, FTT, enlarged kidneys
what disease is caused by deficient uptake of copper?
menkes (kinky hair) disease – X-linked
workup for fatty oxidation disorders?
cbc, cmp, ammonia, CK, lactate, free and acylcarnitine levels,
what disease causes self-mutliation by age 2?
lesch nyhan disease, x-linked
what triad is seen with multiple carboxylase deficiency?
alopecia, skin rash, encephalopathy (treat with biotin)
how do you treat type 2 GSD?
enzyme replacement, high-protein diet
what is the enzyme defect in PKU
phenylalanine hydroxylase (leads to low tyrosine levels because cant convert phe to tyrosine)
