Inborn Errors Of Metabolism Flashcards
What are the main organic acidemias?
“GIMP”
Glutaric acidemia
Isovaleric acidemia
Methylmalonic acidemia
Propionic acidemia
What are the features of organic acidemias?
Glucose: Low NH3: High Ketones: Yes Acidosis: Yes Lactate: High
- 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?
Glucose: Nml NH3: High!!! (low BUN) Ketones: No Acidosis: No Lactate: Nml
- OTC, Citrullinemia, ASA
- Hypotonia
- Respiratory alkalosis
- Vomiting
- Lethargy
- 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?
Glucose: Low NH3: Nml/High Ketones: No Acidosis: Mild Lactate: High
- 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?
Glucose: Low NH3: Nml Ketones: Yes Acidosis: Yes (gap acidosis) Lactate: High
- GSD1, GSD2
- Organomegaly (from glycogen buildup)
- Dx: low fasting glucose + ketones
- Tx: cornstarch
What are the features of mitochondrial disorders?
Glucose: Low NH3: Nml Ketones: Yes Acidosis: Yes Lactate: High
Same as storage disorders
- Elevated pyruvate level, lactic acid level, uric acid level
What are the features of amino acidopathies?
Glucose: Nml NH3: Nml Ketones: No Acidosis: No Lactate: Nml (except in MSUD)
- Subtypes: "PATH"
P: PKU
A: Alkaptonuria
T: Tyrosinemia
H: Homocysteinuria
- 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?
Glucose: Nml NH3: Nml Ketones: No Acidosis: No Lactate: Nml
- Seizures, hiccups, lethargy
- Dx: high glycine
- poor prognosis
What are the features of galactosemia?
Glucose: Low NH3: Nml Ketones: Nml Acidosis: No Lactate: Nml
- 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 Poor feeding Seizures Prone to getting infections No lactic acidosis Treatment: protein restriction
What are the features of methylmalonic acidemia and propionic acidemia?
Poor feeding Vomiting Dehydration Lethargy Hypotonia Tachypnea
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.”
P: Phenylketonuria
A: Alkaptonuria
M: Maple syrup urine disease
H: Homicysteinuria
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?
"HuNiTaG" H: Hurler, Hunter N: Niemann-Pick T: Tay-Sachs G: Gaucher
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
FABRY’C
Foam cells / Febrile episodes
Alpha galactosidase A deficiency / Angiokeratomas
Burning pain in hands and feet (peripheral neuropathy)
Renal failure
YX genotype (male, X-linked recessive)
Ceramide trihexoside accumulation
What are the features of Niemann-Pick disease?
“Nieman Marcus is so fancy, they replaced all of their escalators with CHERRY RED SPHINGO SLIDES. You jumped on, but smashed your belly, causing HSM and hit your head at the bottom, causing NEURO DEFICITS.”
- Sphingomyelinase deficiency
- Accumulation if sphingomyelin in macrophages within the liver and lungs
- Neurologic problems, hepatosplenomegaly, cherry red spot
