Inborn errors of metabolism Flashcards
PKU is a deficiency of what?
Phenylalanine hydroxylase (PAH)
What is the treatment of PKU?
Remove phenylalanine from diet
What reaction does PAH regulate?
Phenylalanine -> tyrosine
Tyrosine is a precursor for what?
DA, L-dopa, melanin
What is the inheritance pattern of PKU?
Aut Rec
What is the phenotype of PKU?
Hyperphenylalaninemia, mental retardation, white matter hyperintensities, seizures, light hair and skin
What kind of amino acids are found in the urine of a patient with MSUD?
Branched-chain ketoacids
What is the inheritance pattern of MSUD?
Aut Rec
MSUD is a deficiency of what?
Branched chain alpha ketoacid dehydrogenase (BCKD)
What is the acute treatment of MSUD?
Eliminate dietary protein intake. Treat cerebral edema if present. Hemodialysis maybe..
What is the chronic therapy of MSUD?
Protein restricted diet supplemented with branched chain amino acid free medical foods (MSUD “coolers”).
Tyrosenemia type I is a deficiency of what?
Fumarylacetoacetate hydrolase (FAH)
What is the inheritance pattern of Tyrosenemia type I?
Aut Rec
What are the 3 presenting forms of Tyrosenemia type I?
- 1-6mo: liver disease
- late infancy: rickets due to renal tubulopathy (Fanconi syndrome) with no obvious liver failure
- porphyria-like attack at any age
In Tyrosenemia type I, which molecules build up which are toxic to the liver and nerves?
Fumarylacetoacetate and succinylacetone
What is the treatment of Tyrosenemia type I?
NTBC which inhibits an enzyme which causes further buildup of tyrosine but prevents production of FAA and succinylacetone. Restrict dietary tyrosine.
Palmoplantar keratosis is a feature of which disease?
Tyrosenemia type I; buildup of tyrosine
What can Tyrosenemia type I do to the eye?
Tyrosine can crystalize in the cornea
What is the clinical presentation of Alkaptonuria?
Black urine, black pigmentation of cartilage and collagen, degenerative arthritis from fourth decade.
Which amino acidopathy presents similar to Marfan if left untreated?
Homocysteinuria
In homocysteinuria, which two molecules are elevated in blood and urine?
Homocysteine and methionine
Homocysteinuria is a deficiency of what?
Cystathionine b-synthase (CBS)
Thromboembolism can be a manifestation of which amino acidopathy?
Homocysteinuria
Premature atherosclerotic disease can be a manifestation of which amino acidopathy?
Homocysteinuria
What is the inheritance pattern of Homocysteinuria?
Aut Rec
Which vitamin is given as a treatment for Homocysteinuria?
B6 (Pyridoxine)
What is the treatment of Homocysteinuria?
B6 (if responsive), restrict dietary protein, oral betaine
What are the general manifestations of urea cycle disorders?
Encephalopathy, coma, irreversible neurologic damage, or death.
Why is it difficult to detect a urea cycle disorder?
Because ammonia levels must be checked. Always check ammonia in a coma.
What are some common triggers of hyperammonemic crises in UCD patients?
Infections, fevers, valproate, vomiting, lots of exercise, chemotherapy.
What is the most common urea cycle disorder?
Ornithine Transcarbamylase (OTC) Deficiency
What is the inheritance pattern of OTC Deficiency?
X-linked
What is the treatment for acute OTC Deficiency?
Ammonia scavenging agents
What are two ammonia scavenging agents?
Sodium phenylacetate and Sodium benzoate
What are some treatment strategies for OTC Deficiency?
Dietary protein restriction, ammonia scavengers, consider liver transplant
The majority of lysosomal storage diseases (LSDs) are inherited in what fashion? What is the exception?
Aut Rec. Exceptions are Fabry and Hunter disease (X-linked).
Are LSDs usually acute or gradual in onset?
Gradual - buildup of molecule and then organ defect leads to dysfunction.
What is the deficient enzyme in Fabry disease?
alpha-galactosidase
What is the deficient enzyme in Gaucher disease?
Glucocerebrosidase (beta-glucosidase)
What is the deficient enzyme in Tay Sachs Type I?
Hexosaminidase A
What is the incidence of all lysosomal storage diseases combined?
1:5,000
Cherry red spots are indicative of which LSD?
Tay Sachs
Blindness is a complication of which LSD?
Tay Sachs
Renal failure is a complication of which LSD?
Fabry
What are the skin manifestations of LSDs?
Courseness
What are the skull (brain) manifestations of LSDs?
Macrocephaly and cognitive regression
What are the eye manifestations of LSDs?
Corneal clouding and cherry red spot
What are the ENT manifestations of LSDs?
Macroglossia with sleep apnea (complication)
What are the liver manifestations of LSDs?
Hepatosplenomegaly with preserved hepatic function
What are the renal manifestations of LSDs?
Proteinuria (Fabry)
What are the skeletal manifestations of LSDs?
Dysostosis multiplex, joint stiffness, short stature
What is Dysostosis Multiplex?
Abnormally bony structure on x rays; vertebral beaking, broad bases of metacarpals and phalanges, scoliosis
“Crumpled tissue paper” appearance in cytoplasm of bone marrow cells is indicative of which LSD?
Gaucher
An Erlenmyer flask deformity of bones is indicative of which LSD?
Gaucher type I - bone marrow infiltration
What is the clinical presentation of Gaucher type I?
Fatigue, bony pain, enlarging abdomen, hepatosplenomegaly, anemia/low platelets.
Which organs are involved in Gaucher?
Liver, spleen, bone marrow (no CNS)
What is the treatment for Gaucher?
ERT
What is the treatment for Tay Sachs?
Supportive
What is the treatment for Fabry?
ERT
What is the treatment for Pompe disease?
ERT
What is the deficient enzyme in Pompe disease?
Alpha-glucosidase
What is the clinical presentation of Tay Sachs type I?
Blindness, seizures, mental/motor deterioration, no hepatosplenomegaly
What is the clinical presentation of Pompe disease?
Infant with progressive muscle weakness and LVH. Adult with proximal muscle weakness and respiratory weakness (sleep apnea).
What is the clinical presentation of Fabry?
Acroparesthesia; pain in palms/soles, esp with fevers. Proteinuria and renal failure. Left ventricular hypertrophy/stroke. Dark red angiokeratomas (bathing suit distribution).
What is the deficient enzyme in Hunter disease?
Iduronate sulfatase
What is the deficient enzyme in Hurler disease?
Alpha iduronidase
SCID is caused by a deficiency in what enzyme?
Adenosine deaminase (ADA)
Lesch-Nyhan is caused by a deficiency in what enzyme?
HPRT