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91 Cards in this Set
- Front
- Back
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CNS signs of mitochondrial disease
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stroke-like episode, microcephaly, encephopathy, central apnea, DD, ataxia, migraine, gray or white matter disease
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GI signs of mitochondrial disease
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liver failure, dysmotility, recurrent vomiting
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Ophthalmologic signs of mitochondrial disease
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optic atrophy, retinopathy, ophthalmoplegia
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Features of MELAS
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Mean onset 10 years
migraine-like attacks stroke-like attacks lactic acidosis dementia or MR seizures |
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Features of MERRF
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progressive myoclonic epilepsy
myopathy reagged red fibers on muscle biopsy MRI abnormalities |
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Most common Kearns-Sayre mutation
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T8993C ATP6
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Features of Pearson "marrow-pancreas" syndrome
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sideroblastic anemia, pancreatic fibrosis and exocrine dysfunction, diarrhea, childhood death, lactic acidosis
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Features of MNGIE
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child/adolescent onset, myopathy with high GI involvement, weight loss, dementia, ophthalmoplegia, progressive leukodystrophy, peripheral neuropathy, lactic acidosis
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Features of Barth syndrome
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dilated cardiomyopathy, neutropenia, skeletal myopathy, lactic acidosis, ultrastructural mitochondrial changes
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Features of Leigh syndrome
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Subacute necrotizing encephalomyopathy, developmental regression, appears in first year of life
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Name some agents that may be used to treat mitochondrial disease
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CoQ10, riboflavin, thiamine, DCA, carnitine, ketogenic diet
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Name 2 important criteria that a condition must have in order for newborn screening to be efficient
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Must occur often enough in population, and there must be a reliable test
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What happens in CPTI deficiency?
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FA can't enter mitochondria, not oxidized. leads to liver disease, hypoglycemia (can't fast), and increased carnitine
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In CPTI deficiency, what precautions need to be taken for anesthesia?
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Glucose before and after
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What nationaliity has a high incidence of LCHAD?
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Finnish
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When does LCHAD 1st appear?
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first year of life
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Clinical signs of FA oxidation defects
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FTT, vomiting, coma, poor feeding, lethargy, seizures, liver dysfunction
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What mutation is most often the cause of MCAD?
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K304E (A985G)
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What is the major presentation of hypoketotic hypoglycemia?
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MCAD
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What condition, if left untreated, can present with liver dysfunction and can be misdiagnosed as Reye syndrome?
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MCAD
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What is the best way to check siblings of a child with MCAD?
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Must do genotyping, because metabolites could be normal when the kids are well.
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Common symptoms of SCAD
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DD, muscle hypotonia
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The most common SCAD mutation
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T529C
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What percent of SCAD mutants are asymptomatic?
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majority
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The marker for SCAD
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butyrylcarnitine
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Name 6 times in which a metabolic disorder should be considered.
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1. catastrophic neonatal presentation
2. biochemical disturbances 3. liver disease or dysfunction 4. neurologic features 5. myopathy or cardiomyopathy 6. signs of a storage disease |
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Name 5 types of metabolic disease in which symptoms are so severe that they appear prenatally, mom can't restore defect
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1. Peroxisomal disease (Zellweger)
2. Fatty acid oxidation defects 3. Mitochondrial disease 4. Disorders of glycosylation 5. Defects in cholesterol synthesis |
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Features of neonatal catastrophe
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feeding problems, floppy, vomiting, hypotonic, lethargy, seizures, coma, tachypnea, septic-like, altered reflexes
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Babies with lysosomal storage disorders are susceptible to what infections?
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ear infections, respiratory infections, splenomegaly
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HIgh ammonia can diagnose what types of metabolic disorders?
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urea cycle, organic acidemia, fatty acid oxidation defects, mitochondrial disorders
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CHRONIC symptoms of urea cycle disorders
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poor feeding, anorexia, protein aversion, vomiting, DD, hypotonia
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ACUTE symptoms of urea cycle disorders
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vomiting, lethargy, coma, seizures, high ammonia, respiratory alkalosis
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Features of the urea cycle defect Argininosuccinic aciduria.
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chronic liver enlargement/dysfunction
may have kinky hair |
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Features of the urea cycle disorder Arginase deficiency
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chronic neurologic presentation (DD, spastic diplegia)
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CHRONIC symptoms of organic acidemias
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poor feeding, anorexia, maybe protein aversion, vomiting, hypotonia, DD/MR
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ACUTE symptoms of organic acidemias
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vomiting, lethargy, coma, seizures, metabolic ketoacidosis, maybe high ammonia, maybe hypoglycemia
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Features of the organic acidemia Biotinidase Deficiency
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hypotonia, seizures, eczema, alopecia, hearing loss, retinal disease
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Features of the organic acidemia Glutaric acidemia Type I
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Macrocephaly, unusual brain fluid due to bursting, retinal hemorrhage (child abuse-like),stroke-like features causing dystonia and motor impairment
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Organic acids in the urine can be indicative of what types of disorders?
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organic acidemias, fatty acid oxidation defects, mitochondrial disorders
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Urine Ketones are helpful in diagnosing what kind of defect?
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organic acidemia, fatty acid oxidation defects, glycogen storage disease I
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Acute metabolic liver disease could mean which metabolic disorders?
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galactosemia, tyrosinemia type I
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Rickets can be seen in which metabolic disorders?
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Those with acute liver disease--galactosemia, tyrosinemia type I
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What disorder is associeated with accumulated sphingomyelin, leaving odd spheres on histology?
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Niemann-Pick
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Acute fatty liver can occur with what types of defects?
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Fatty acid oxidation, urea cycle disorders
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Neurologic features of Zellweger
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prenatal onset
dysmorphic hypotonic seizures liver disease death in months |
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Neurologic features of Pompe
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infantile onset
hypotonia, weakness cardiomyopathy death in 1-2 years |
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Features of Menkes disease
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neonatal onset
profound DD kinky hair hypopigmntation hypotonia Wormian bones Bladder diverticuli hypopigmentation death in 1st year |
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Tyrosinemia is most common in what population?
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French Canadian
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CNS symptoms on Tyrosinemia Type I
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neurologic crises (porphyria-like), painful peripheral neuropathy, hypertension, tachycardia, arching, self-mutilation, weakness, respiratory failure
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What enzyme is defective in Tyrosinemia Type I?
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FAH
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WHy is high tyrosine not enough to diagnose Tyrosinemia Type I?
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Because high tyrosine can also occur with any liver disease
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3 possible treatments for Tyrosinemia Type I
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low protein diet, NTBC (an enzyme inhibitor), liver transplant to provide enzyme
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What accumulates to cause disease in Tyrosinemia Type I?
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succinylacetone
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Which population has the highest incidence of homocystinuria?
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Ireland
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2 common homocystinuria mutations
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G307S (Irish)
I278T (homozygous are B6 responsive) |
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2 populations with high incidence of nonketotic hyperglycinemia
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British Columbia, Finland
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CNS features of early-onset nonketotic hyperglycinemia
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profound hypotonia
lethargy apnea seizures, myoclonic jerks severe MR |
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What enzyme is deficient in nonketotic hyperglycinemia?
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Glycine cleavage enzyme complex
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How is nonketotic hyperglycinemia diagnosed?
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High glycine in CSF.
May also confirm by absent enzyme in liver. |
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Acute symptoms of urea cycle disorder during hyperammonemic episode
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poor appetite, vomiting, hyperventilation, acute fatty liver, lethargy, hypotonia, coma, seizures
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Name some leukodystrophies
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Krabbe, Metachromatic leukodystrophy, Canavan, X-linked adrenoleukodystrophy
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Which leukodystrophy is associated with eye disease/vision loss?
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Metachromatic leukodystrophy, also X-linked
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Clinical signs of a fatty acid oxidation defect
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fasting intolerance, vomiting, lethargy, coma, cardiomyopathy, liver enlargement or dysfunction
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Biochemical signs of a fatty acid oxidation defect
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low carnitine
abnormal organic acids, acylcarnitines, acylglycines, maybe high ammonia, hypoketotic hypoglycemia |
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Carnitine levels can be halpful in diagnosing what types of disorders?
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FA defects, organic acidemias, mitochondiral disorders--these compounds can bind carnitine
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Which organic acidemia is associated with retinal hemorrhaging?
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Biotinidase deficiency
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Features of storage diseases in general
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hepatosplenomegaly, dysmorphic features, skeletal dysplasia, eye findings (corneal clouding, cherry red spot), neurodegeneration
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REcurrent ear infections can be associate4d with what kinds of metabolic disorders?
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Storage disorders like mucopolysaccharidoses--storage vescicles in eustation tubes
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Enzyme that's not working in MSUD
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branched chain keto acid dehydrogenase
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features of MSUD
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starts 3-4 days after birth--poor feeding and vomiting, lethargy, hypotonia or hypertoia, seizures, apnea, cerebral edema leading to hernia
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What would be the newborn screen results for MSUD?
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plasma AA=increased leucine, valine, isoleucine
urine organic acids=increasedbranched chain keto acids |
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What would be the newborn screen results for PA?
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plasma AA=increased glycine
blood organic acids =increased propionyl carnitine urine organic acids=increased propionate |
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What would be the newborn screen results for MA?
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plasma AA=increased glycine
blood organic acids =increased propionyl carnitine and MM-carnitine urine organic acids=increased methylmalonate |
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Immediate treatment for acute organic acidosis
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stop all protein, give carbs and fats (dextrose), rehydrate, electrolytes, possibly sodium bicarbonate
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Treatment for PA, in a nutshell
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low-protein diet, biotin, maybe carnitine, GI tube
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Long-term outcome of untreated PA
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episodes of coma, MR, cerebral palsy, metabolic stroke, dermatitis, infections, pancreatitis, poor growth, dystonia and abnormal movements, cardiomyopathy
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Immediate treatment for acute urea cycle defect
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Give glucose. Ammonia breaks down protein, glucose will reverse the process by releasing insulin from pancreas, insulin very anabolic. Can also do dialysis to remove ammonia from body
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Why is infection associated with acute attacks of urea cycle defects?
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Because when we have an infection, we become catabolic. Proteins are broken down to AAs, and all macromolecules are brojken down. Bone marrow produces WBCs, which release cytokines. They attach to muscles and break them down, releasing AAs, whcih turn to ammonia.
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What urine metabolites are high in a PKU test?
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neopterin, biopterin
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What is measured in the newborn screens for organic acidemias?
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acylcarnitines
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What is measured to confirm organic acidemias--3 things?
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blood AAs
blood aylcarnitines urine organic acids |
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Which GALT mutation is the Duarte mutation?
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N314D
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Features of glycogen storage disease Type I
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babies can't sleep through night, doll's face, protruding abdomen with liver enlargement, truncal obesity, easy bruising
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What is the problem in glycogen storage disease type I?
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Can't break down glycogen into glucose, results in hypoglycemia. Results in too many triglycerides. Glycogen and fat accumulate in liver.
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What metabolic condition can result in malignant adenomas?
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glycogen storage disorder type I
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Another name for glycogen storage disorder type II
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Pompe disease
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Features of infantile-onset Pompe
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doll's face, hypotonia and weakness, cardiomyopathy with distinctive EKG, elevated creatine kinase
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Features of childhood-onset Pompe
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weakness that gets worse
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What goes wrong in Pompe disease?
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Glycogen cannot be broken down and accumulates in lysosomes
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Prognosis for babies with Pompe
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Death due to cardiac failure in first year of life
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Describe briefly what happens in an acute episode with MCAD
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hypoglycemia during illness, with low ketone production
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