Flashcards in Inborn Errors Of Metabolism Deck (25):
What are the main organic acidemias?
What are the features of organic acidemias?
- DOL 2
- Thrombocytopenia, granulocytopenia
- Dx: urine organic acid levels
- Tx: hydration, stop protein intake, IV glucose and ammonia scavengers, L-carnitine
What are the features of urea cycle defects?
NH3: High!!! (low BUN)
- OTC, Citrullinemia, ASA
- Respiratory alkalosis
- Dx: check serum citrulline, arginine, ASA, urine orotic acid. low arginine, no citruline, high urine orotic acid.
- Tx: restrict protein, NH3 scavengers (benzoate, phenylbutarate)
What are the features of fatty acid metabolism disorders?
- MCAD, LCAD, VLCAD
- Induced by stress, fasting -> nonketotic hypoglycemia
- Do not present in the first week of life
- Possible hepatomegaly with transaminitis
- Dx: low glucose and low ketones. Get carnitine and acylcarnitine levels.
- Tx: IV glucose
What are the features of storage diseases?
Acidosis: Yes (gap acidosis)
- GSD1, GSD2
- Organomegaly (from glycogen buildup)
- Dx: low fasting glucose + ketones
- Tx: cornstarch
What are the features of mitochondrial disorders?
Same as storage disorders
- Elevated pyruvate level, lactic acid level, uric acid level
What are the features of amino acidopathies?
Lactate: Nml (except in MSUD)
- Subtypes: "PATH"
- Dx: high levels of specific amino acid that cannot be broken down in serum and urine
- Tx: Limit intake of specific amino acid
What are the features of hyperglycinemia?
- Seizures, hiccups, lethargy
- Dx: high glycine
- poor prognosis
What are the features of galactosemia?
- GALT deficiency
- Patients present with GNR sepsis
- Can present with vomiting, diarrhea, lethargy, hepato-megaly, jaundice, hypoglycemia, seizures
- Dx: high g1p, non-glucose reducing substances in urine, low GALT activity in RBCs
- Tx: lactose and galactose free diet
What are the features of isovaleric acidemia?
Sweaty feet smell
Prone to getting infections
No lactic acidosis
Treatment: protein restriction
What are the features of methylmalonic acidemia and propionic acidemia?
MMA: tx with B12
Propionic: tx with biotin
What are the features of ornithine transcarbamylase deficiency?
- X-linked (much more symptomatic in boys than in girl carriers, who only get symptoms when they are sick)
- High urine orotic acid
What are the features of von Gierke's disease?
- GSD I
- Glucose-6-phosphatase deficiency -> can't break down glycogen -> glycogen deposits in organs
- Doll like face
- Only presents when there is hypoglycemia
- Hypoglycemia, ketoacidosis (from fat breakdown), lactic acidosis, hyperuricemia
- Tx: low carb diet, complex carbs (cornstarch)
What are the features of Pompe disease?
- GSD II
- Lysosomal disorder: deficiency of lysosomal alpha 1,4 glucosidase
- Presentation: baby with hypotonia, macroglossia, and hypertrophic cardiomyopathy
- Glycogen deposits in organs -> organomegaly
- No hypoglycemia because other glycogen stores can be broken down
- Dx: ⬆️ glycogen in lysosomes, ⬆️ LDH, ⬆️ CK
What are the aminoacidopathies?
"PAM is a Hot tamale."
M: Maple syrup urine disease
What are the features of PKU?
- Musty/mousy order
- Light colored skin and hair
- Developmental delay -> severe MR
- Possible eczema like rash
- Septal defects
- Dx: no tyrosine
- Tx: low phenylalanine diet (overtreating-> lethargy, rash, diarrhea)
- If pregnant women don't control diet -> microcephaly, congenital heart defects, cognitive defects
What are the features of alkaptonuria?
- Problem with phenylalanine and tyrosine metabolism
- Black urine
- Excess homogentisic acid deposits in joints and heart valves
- Dx: homogentisic acid levels in urine
- Tx: limit intake of phenylalanine and tyrosine
What are the features of maple syrup urine Disease?
- Early presentation (first week of life)
- Sweet smelling urine, tachypnea, lethargy, untreated -> encephalopathy, seizures
- High ammonia, high ketones, hypoglycemia
- Dx: serum with high levels of VIAL (valine, isoleucine, alloisoleucine, leucine)
- Tx: diet free of branched-chain amino acids
What are the most common lysosomal storage diseases?
H: Hurler, Hunter
What are the features of mucopolysaccharidoses?
- Hunter and Hurler syndromes
- Due to a missing or dysfunctional lysosomal enzymes needed to break down a long carbohydrate
- Result in the accumulation of dermatin, keratin, and heparin sulfate in the brain, bones, connective tissue, and other organs
- Progressive physical deformities and cognitive problems
- Coarse features, thick eyebrows, organomegaly, progressive joint contractures, growth deceleration, progressive deafness
- Dx: excessive urine mucopolysaccharides
What is the difference between hunter syndrome and hurler syndrome?
Hunter syndrome has no corneal clouding.
- Imagine X Marks the Spot. A Hunter has good vision, so he can make the kill by aiming for the X.
What are the features of Tay-Sachs disease?
- Autosomal recessive
- Deficiency of Hexosaminidase A enzyme
- Develop normally until about nine months
- Macrocephaly, exaggerated startle reflex, cherry red spot on the retina, death by age 4
- No organomegaly
What are the features of Gaucher disease?
- Hepato-megaly, thrombocytopenia, easy bruisability, osteosclerosis and lytic lesions with bone pain, short stature
What are the features of Fabry disease?
- Opacities of that eye, vascular disease of the kidney, heart or brain, orange colored skin lesions, no organomegaly
Foam cells / Febrile episodes
Alpha galactosidase A deficiency / Angiokeratomas
Burning pain in hands and feet (peripheral neuropathy)
YX genotype (male, X-linked recessive)
Ceramide trihexoside accumulation