Repro 16 - Genetic Disorders: AR And X-linked. Flashcards
What is Cystic Fibrosis? What is the cause?
A defect in the transmembrane protein that puts chloride from the cell into lumen of the pancreatic ducts and airways; Sodium and water follow chloride. Clinically causes recurrent pulmonary infections (Pseudomonas), bronchiectasis, pancreatic insufficiency, Meconium ileus in newborns, infertility in males (absence of vas deferens), fat soluble vitamin deficiencies; failure to thrive. Salty-testing sweat. Caused by defect on CFTR gene on chromosome 7.
What is a rapid way to test for Cystic fibrosis?
Chloride sweat test: increase in chloride in sweat is diagnostic (Chloride greater than 60 mEq/L)
What is the treatment for cystic fibrosis?
N-acetylcysteine (mucolytic). Antibiotics (most of the time we do not use fluoroquinolones in pediatric patients except here). Pancreatic enzyme and fat soluble replacement.
What is Fabry disease and what is the cause?
X-linked. Caused by deficiency of alpha-galactosidase which leads to accumulation of ceramide trihexoside. Symptoms begin in early childhood: pain by neuropathy and ischemia, Renal failure, HTN, cardiomyopathy, angiokeratomas.
Which disease is the most common of the lysosomal storage diseases?
Gaucher disease.
What is Gaucher disease and what is the cause?
Autosomal recessive. Most common lysosomal storage disorder. Caused by deficiency in glucocerebrosidase, leading to accumulation of glucocerebroside. Symptoms are hepatosplenomegaly, painful bony lesions, anemia, fatigue, thrombocytopenia. Macrophages looks like crumpled tissue paper.
What is Niemann-Pick disease and what is the cause?
An autosomal rece. Caused by deficiency in sphingomyelinase causing accumulation of sphingomyelin. Causes hepatosplenomegaly and thrombocytopenia. Accumulation in cerebellum causes ataxia, dysarthria, dysphagia, gradual worsening of intellectual function. “Cherry-red spot” in the macula. Foam cells.
What is Tay-Sachs disease and what is the cause?
An autosomal recessive, caused by deficiency in hexosaminidase A, leading accumulation of GM2 ganglioside. Causes worsening of mental and physical abilities starting around 6 months; death by age 4. “Cherry-red spot” on the macula.
What is one clue to separate b/w Tay-Sachs and Nieman-Pick?
No hepatosplenomegaly in Tay-Sachs.
What is the Krabbe disease and the cause?
Autosomal recessive, caused by deficiency in galactocerebrosidase, leading to accumulation of galactocerebroside. This disease affects myelin sheaths, causing peripheral neuropathy, seizures, optic atrophy, weakness, developmental delay. Symptoms begin at 3-6 months, death before age 2.
What is Metachromatic leukodystrophy and the cause?
Autsomal recessive, caused by deficiency in arylsulfatase A, leading to accumulation of cerebroside sulfate. This disease affects myelin sheaths, causing muscle wasting, weakness, progressive vision loss, dementia.
What is Hurler syndrome and what is the cause?
An autosomal rece, caused by deficiency in alpha-L-iduronidase, causing an accumulation of heparin sulfate and dermatan sulfate. Causes progressive deterioration, coarse facial features, hepatosplenomegaly, intellectual disability, corneal clouding.
What is Hunter syndrome?
X-linked. Deficiency in iduronate sulfatase, causing an accumulation of heparan sulfate and dermatan sulfate. Milder form of Hurler syndrome, causing hepatosplenomegaly and intellectual disability.
How can we differentiate b/w Hurler syndrome and Hunter syndrome sole based on symptoms?
Hunter syndrome does not have corneal clouding, later onset and more aggressive behavior.
What disease has optic atrophy, myelin sheath involvement, and galactocerebrosidase deficiency?
Krabbe disease.
