Inherited Metabolic Diseases Flashcards
A neonate dies from cardiac failure. A biopsy of muscle is taken and shown below. What is shown in the biopsy? What is this pathognomonic for? What disease did the patient die from? What is the most serious form of this disease?
Periodic acid - Schiff stain showing large vacuoles filled with glycogen granules; Type II Glycogenosis (Acid Maltase Deficiency); Pompe Disease
A patient presents with severe liver dysfunction and growth retardation. What type of glycogenosis does he have? What is the molecular pathology of this disease.
Type III Glycogenosis (Debranching Enzyme Deficiency); Lack of debranching enzyme stops glycogen hydrolysis
A patient comes in for his general check up and states that he has severe muscle cramps when exercising. Genetic testing is performed and reveals that the patient has a glycogenosis. What glycogenosis does he have? What is the enzyme deficiency? What is seen on histologic analysis?
Type V, McArdle Disease; Myophosphorylase Deficiency; Glycogen accumulation in subsarcolemmal distribution
What is the presentation of a person with Type VII Glycogenosis? What enzyme is deficient?
Similar to a person with McArdle disease (muscle fatigue on exertion); Phosphofructokinase;
What is carnitine required for? How is a deficiency inherited? What is seen on biopsy?
Transport of long-chain fatty acids into mitochondria; Autosomal Recessive; Accumulation of lipids in the sarcoplasm
What occurs when a patient has a carnitine palmitoyltransferase deficiency? Clinical presentation?
Cannot metabolize long-chain fatty acids because unable to transport them into the mitochondria; Muscle pain after exercise and possible myoglobinuria
What is the mechanism of inheritance for mitochondrial DNA?
From the mother!
What must occur for a mitochondrial disease to be symptomatic?
The fraction of mutant mtDNA must exceed a critical value!
A patient has a mitochondrial disease. What is shown in the image below?
Ragged Red Fibers - accumulation of mitochondria
What is Kearns-Sayre syndrome?
Mitochondria neurologic syndrome with progressive opthalmoplegia, retinal pigmentary degernation, cardiac arrhythmia
What is MELAS neurologic syndrome?
Mitochondrial disease with mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes
What is MERRF?
Neurologic mitochondrial syndrome resulting in myoclonic epilepsy, and ragged red fibers
A patient with exercise intolerance and muscle weakness is found to have a difficult maintaining ATP/ADP ratio. What disease does he likely have?
Myoadenylate deaminase deficiency
A patient experiences episodic muscular weakness and occasionally complete paralysis followed by rapid recovery. What inherited disease does he have? What are the three subtypes of the disease?
Familial Periodic Paralysis resulting from impaired electrolyte flux; Hypokalemic, Hyperkalemic, Normokalemic
