Inherited Metabolic Diseases Flashcards
Pedia and genes!
Differentiate between penetrance from expressivity
Penetrance is a measure of the proportion of individuals with a given genotype who will show the phenotype
Expressivity refers to the severity of disease in an affected individual
Which appear soon after birth autosomal dominant or recessive?
Recessive
Why do some mitochondrial disease have a mendelian pattern of inheritance rather than a maternal/mitochondrial one?
85% of of protein components of the respiratory chain are coded in nuclear DNA
Which of the mitochondrial oxidative phospohrylation enzymes is most usually affected by mitochondrial disorders?
Cytochrome 4: Cytochrome-C Oxidase
Leads to lactic acidosis
What kind of seizures point to hereditary metabolic disease?
Recurrent non-convulsive episodes of impaired consciousness or
intractable seizures in infants or young children or infantile spasms and progressive myoclonic seizures in the absence of neonatal HIE
What are the 3 patterns of neonate behavior predictive of neurologic abnormality later in life?
- Hyperkinetic hypertonic
- Apathetic hypotonic
- Unilateral or hemidystonic
What are the 3 most frequently identified hereditary metabolic disease?
- Phenylketonuria
- Hyperphenylalaninemia
- Congenital hypothyroidism
Describe which disease based on urinary screening tests
- Green on ferric chloride
- Navy blue on ferric chloride
- on ferric chloride but + benedict reaction
- Purple on ferric chloride
- Green brown on ferric chloride
What are the findings on urinary screening tests for cystinuria, homocystinuria and tyrosinemia?
- Phenylketonuria: Green on ferric chloride
- Maple syrup urine disease: Navy blue on ferric chloride
- Galactoesmia or fructose intolerance - on ferric chloride but + benedict reaction
- Propionic acid acidemia or methylmalonic aciduria: Purple on ferric chloride
- Histidinemia
Positive on nitroprusside– in addtion tyrosinemia also has a transient pale green color on ferric chloride and + DNPH
Besides phenylketonuria what other illness should be suspected in a patient with accumulated phenylalanine causing myoclonic seizures with a poor level of responsiveness and generalized hypotonia?
Biopterin deficiency
TetrahydroBiopterin is a cofactor of phenylalanine in its metabolism of phenylalanine to tyrosine
Galactosemia presents with vomiting, diarrhea and FTT after ingestion of milk. What are the possible neurologic complications of the condition?
- Cataracts form as a result of the accumulation of galactitol in the lens.
- IQ 85
- Cerebral bleed from thrombocytopenia
Where does propionyl coA come from? Accumulation of this substance due to missing propionyl coA carboxylase activity leads to?
Odd number fatty acids and certain amino acids like methionine threonin and valine
Organic aciduria– Propionic acidemia
Determine which acidemia is being described:
- Metabolic acidosis, lethargy, vomiting, convulsions and coma with early death in about half the patients and developmental retardation in those who survive.
- Sweaty foot syndrome– smell of stale perspiration
- Acidosis with vomiting and hyperglycemia with MCAs and cardiomyopathy
- ALL: Metabolic acidosis, lethargy, vomiting, convulsions and coma with early death in about half the patients and developmental retardation in those who survive.
- Isovaleric acidemia: Sweaty foot syndrome– smell of stale perspiration
SI VAL AMOY PAWIS!
- Type 2 glutaric acidemia: Acidosis with vomiting and hyperglycemia with MCAs and cardiomyopathy
What is the notable finding in the CSF of nonketotic hyperglycemia? What treatment can be given to prevent seizures and coma?
Increased CSF glycine
Dextromethorphan which blocks glycine receptors and administration of sodium benzoate to divert nitrogen from the ureagenesis cycle
What is the inherintance pattern of inherited hyperammonemias? Deficiencies of enzymes in the Krebs Henseleit urea cycle
Autosomal recessive except for OTC X linked dominant
Ornithine transcarbamylase deficiency
Which inherited hyperammonemia?
- Excessive dryness and brittlness of hair (Trichorrhexis nodosa)
- Spastic diplegia
- Excessive dryness and brittlness of hair (Trichorrhexis nodosa): Argininosuccinic aciduria
- Spastic diplegia: Arginase deficiency
What of IEM manifests as encephalopathy and brain edema after a high protein meal?
Inherited hyperammonemias
Maple syrup urine disease results in the accumulation of which amino acids?
Branched chain AA: lecucine, isoleucine, valine and keto acids
Alpha hydroxybutyric acid accounts for the maple syrup odor
Two treatment strategies for branched chain aminoacidopathies?
- Food restriction
2. Thiamine 30-300mg in some
What vitamin should be administered with:
- Glutaric acidemia
- MSUD
- Biotinidase deficiency
- Methylmalonic acidemia
- Glutaric acidemia: Riboflavin
- MSUD: Thiamine
- Biotinidase deficiency: Biotin
- Methylmalonic acidemia: B12
Differentiate leukodystrophy from lysosomal storage disease.
Leukodystrophy: Progressive symmetrical and usually massive destruction of the white matter of the brain and sometimes of the spinal cord
Lysosomal storage disease: genetic deficiency of enzymes necessary for the degradation of peptide linkages in the intracytoplasmic lysosomes causing nerve cells to become engorged with materaila that they would ordinarily degrade.
Most of LSD are ______
Sphingolipidoses, intracellular lipids that all have ceramide as their basic structure but each with a different oligosaccharide
Determine the primary deficiency of the following lysosomal storage diseases:
- Tay Sachs Disease/ GM2 gangliosidosis
- Infantile Gaucher disease
- Infantile Niemann-Pick Disease
- GM2 Gangliosidosis/ Pseudohurler syndrome
- Krabbe disease/ Globoid cell leukodystrophy
- Sandhoff disease/ GM2 Gangliosidosis
- Tay Sachs Disease/ GM2 gangliodisosis: Hexosaminidase A alpha subunit deficiency
- Infantile Gaucher disease: Glucocerebrosidase
- Infantile Niemann-Pick Disease: Sphingomyelinase Deficiency
- GM2 Gangliosidosis/ Pseudohurler syndrome: Beta galactosidase deficiency
- Krabbe disease/ Globoid cell leukodystrophy: Galactocerebrosidase deficiency GALC mutation
- Sanhoff disease/ GM2 Gangliodosis: Hexomsaminidase deficiency beta subunit
What is observed in more than 90% of all retinas in patients with Tay Sachs disease?
Cherry red spot due to degeneration of macular cells exposing the underlying red vascular choroid surrounded by a whitish gray ring of retinal cells distended with ganglioside
Where else can a cheery red spot be found?
Sandhoff disease Niemann-Pick disease A to D GM1 gangliosidosis Metachromatic leukodystrophy Farber lipogranulomatosis
Neuronal ceroid lipofuscinosis– bull’s eye maculopathy not real cherry red spot
What are the early eye signs of Gaucher disease?
Bilateral strabismus and oculomotor apraxia
What are the 3 important labs in Gaucher disease– type 2 neuronopathic form?
Unable to degrade glucocerebroside
- Increase in serum acid phosphatase
- Gaucher cells (histiocytes wrinkled cytoplasm and eccentric nucleus) in marrow smears and liver and spleen
- Deficiency of glucocerebrosidase
What are the 2 important lab findings in Niemann Pick disease?
Unable to breakdown sphingomyelin
- Deficiency of sphingomyelinase
2. Vacuolated histiocytes “foam cells” in bone marrow or vacuolated blood lymphocytes
Why are patients with Krabbe disease/ Globoid cell leukodystrophy both hypotonic and with babinski sign?
Galactocerebrosidase deficiency
Because there is both corticospinal tract damage and neuronopathy in the cord.
BUT in addition there is also a concomittant denervating demyelinating process causing a polyneuropathy
In Krabbe disease/ globoid cell leukodystrophy which areas of the brain show symmetrical increased signal that is non enhancing?
Internal Capsulses and basal ganglia
What is the characteristic cell found in Krabbe disease?
Globoid cells which are large histiocytes containing the accumulated metabolite
Compare with Gaucher cells in gaucher disease and foam cells in Niemann pick which are vacuolated histiocytes
What breakthrough treatment was discovered for Krabbe disease/ Globoid cell leukodystrophy?
Transplanted umbilical cord hematopoietic cells given to ASYMPTOMATIC babies– prenatal diagnosis or soon after birth
What breakthrough treatment was discovered for Krabbe disease/ Globoid cell leukodystrophy?
Transplanted umbilical cord hematopoietic cells given to ASYMPTOMATIC babies– prenatal diagnosis or soon after birth
What enzyme is missing in Farber disease?
Ceramidase– there is widespreas lipid storage in neurons and granulomas of skin
An X-linked dominant disease of infancy that has a mutatation in the gene coding proteolipid protein (PLP1) one of 2 basic myelin proteins is called?
Pelizaeus-Merzbacher Disease
What are the only 2 leukodystrophies in which nystagmus has been an invariable finding?
Pelizaeus-Merzbacher and Cockayne syndrome
BUT CS is autosmal recessive
Diagnosis? Leukodystrophy wiht behavioral regression, enlarging head, MRI with abnormal white matter hyperintensity with an evelated N-acetyl aspartate peak in MRS and elevated urinary NAA?
Canavan disease/ aka spongy degenration of infancy
Deficiency in aminoacylase II which is responsible for the breakdown of NAA.
What leukodystrophies have large brains?
- Tay sachs disease/GM2 gangliosidosis
- Alexander disease
- Krabbe disease
- Canavan disease
large TACK! Brain atTACK! :-)
What genetic mutation leads to what characteristic histopathologic features of Alexander disease?
GFAP mutation –> Rosenthal fibers (glial degradation products) in distinctlive eosinophilic hylaine bodies
What disease? Hepatic cerebral degeneration characterized by POLG mutation, walnut brain on histopath, progressive disease of cerebral GRAY matter, seizures diffuse myoclonic jerks, microcephaly.
Alpers disease
What is also known as the spongy degeneration of infancy due to ASPA mutation?
Canavan disease
The cerebrohepatorenal syndrome due to PEX1 mutation is AKA?
Zellweger disease, a peroxisomal disease due to deficiencies in peroxisomal enzyme deficiencies
diagnosed by 5x increase in VLCFA
What bone abnormalities can be seen Zellweger syndrome?
Stippled irregular calcifications of the patellae and greater trochanters
What is known as the oculocerebrorenal syndrome due to OCRL mutation? One of the closest ddx to Zellweger syndrome. What physical findings differentiate it?
Lowe syndrome. The preponderance of eye symptoms: glaucoma, large eyes, corneal opacity, blindess, BILATERAL CATARACTS PRESENT AT BIRTH, nystagmus
What is AKA as kingky or steely hair disease due to hair that is lusterless, depigmented and feels like wool– breaking easily and looks twisted (pili torti) under the microscope?
What element is not absorbed from the GI tract?
Menkes disease
Copper
What ratio of substances diagnoses Menke’s disease?
Dopamine to NE.
Dopamine beta hydroxylase is copper dependent therefore low activity in Menke’s. The ratio would be high in Menke’s disease.
Which IEM?
- Acousticomotor obligatory startle
- Abolished tendon reflex with babinski sign
- Trismus, strabismus, opisthotonos
- Intermittent hyperventilation
- Tay sachs: Acousticomotor obligatory startle
- Krabbe, Leigh, metachromatic leukodystrophy: Abolished tendon reflex with babinski sign
- Gaucher disease: Trismus, strabismus, opisthotonos
- Leigh disease and congenital lactic acidosis: Intermitten hyperventilation
Which IEM?
- Rapid pendular nystagmus
- Macular cherry red spots
- Corneal opacification
- Cataracts
- Rapid pendular nystagmus: Pelizeus merzbacher, Cockayne syndrome
- Macular cherry red spots: Tay sachs, Sandhoff, Niemann pick, Farber, Metochromatic leukodystrophy
- Corneal opacification: Lowe, GM1 gangliosidosis
- Cataracts: Lowe, Zellweger
Which IEM?
- Enlarging head without HCP
- Multiple arthropathies and raucous dysphonia
- Abnormal histiocytes in marrow smears
- Colorless friable hair
- Enlarging head without HCP: Alexander disease, Canavan, Tay sachs
- Multiple arthropathies and raucous dysphonia: Farber
- Abnormal histiocytes in marrow smears: Gaucher, Niemann-pick, GM1 gangliosidosis, Farber, Krabbe
- Colorless friable hair: Menke’s disease
Which among these predominantly affect the gray matter? Poliodystrophies Tay Sachs Sandhoff Krabbe Leigh Alexander Canavan Pelizaeus merzbacher Alpers Gaucher Schilder
Purely neurologic: Tay Sachs Sandhoff Leigh Alexander
Affects other systems as well:
Alpers
Gaucher
The rest are white matter: Krabbe, Canavan, Pelizaeus Merzbacher, adrenoleukodystrophy, metachromatic leukodystrophy
Which IEM causes visceromegaly?
Niemann pick Gaucher Pompe Farber Sandhoff
Which among the poliodystrophies present with myoclonic seizures with associated cortical blindness and deafness?
Which among the leukodystrophies of infancy will have tonic spasms?
Alpers
Krabbe
Which poliodystrophy has foam cells in bone marrow, diffuse pulmonary infiltrates and demineralization of bone?
Niemann Pick
Which among the leukodysrophies of infancy can survive to adulthood?
Pelizaeus merzbacher
Which leukodystrophy of infancy also presents with slowed nerve conduction, metachromatic bodies on urine and can be diagnis can be supported by sural nerve biopsy?
Metachromatic leukodystrophy
In amino acidurias how do the amino acids end up urine?
Defect in renal transport
What is the phenotype of phenyketonuria patients?
- Blue eyed
- Fair skin and hair
- Skin rough and dry from eczema
- MUSTY BODY ODOR
What acid in the blood and csft and urine is seen in PKU patients?
Phenylpyruvic acid apart from high levels of serum phenylalanine
Identify what color the urine will be with the Guthrie test (Ferric chloride).
- Phenylketonuria
- Histidinemia
- Maple syrup urine disease
- Propionic and methylmalonic acidemia
- Ketones or salicylates in the urine
- Phenylketonuria: Emerald green that fades in 20 to 40 mins
- Histidinemia: Green brown color that is PERMANENT
- Maple syrup urine disease: Navy blue
- Propionic and methylmalonic acidemia: Purple
- Ketones or salicylates in the urine: Purple as well
What aminoacids need to be restricted for patients with hereditary tyrosinemia?
Tyrosine and phenylalanine
Enumerate the key clinical 3 symptoms and signs of Hartnup disease?
- Intermitted red scaly rash over the face neck hands and legs that is triggered by sunlight, emotional stress and sulfonamide drugs
- Emotional lability, uncontrollable tempre, confusional hallucinatory psychosis
- Episodic cerebellar ataxia
What is responsible for the pellagrous skin changes in Hartnup disease?
Treatment?
Impaired intestinal absorption of tryptophan and loss in urine reduce its availability for synthesis of niacin and accounts for the skin changes
Avoid the sun and sulfonamide drugs, give nicotinamide and L tyrpythophan ethyl ester
What are the two components of Behr disease?
Familial cerebellar ataxia and retinal degeneration
What leukodystrophy results from a mutation in the gene for enzyme arylsulfatase A which prevents the conversion of sulfatide to cerebroside WHICH IS A MAJOR COMPONENT OF MYELIN?
Metachromatic leukodystrophy from an arylsulfatase deficiency
What is contained in the metachromatic granules in engorged macrophages seen on the sural nerve biopsy of metochromatic leukodystrophy?
Sulfatide–> stains brown-orange with aniline dyes
What organomegaly clinches the diagnosis of gaucher disease? Diffuse myoclonus, horizontal gaze palsy, dementia, trismus, rigidity of limbs
What type of gaucher occurs in early childhood to early adulthood?
Spleen
3
Late onset Niemann-Pick disease Type C and D have what eye signs?
Paralysis of horizontal AND vertical gaze
What two lipids can be found in neuronal ceroid lipofuscinoses (Batten disease)?
Ceroid and lipofuscin
What is the adult type of Batten disease?
Juvenile?
Childhood?
Infancy?
Kufs
Spielmeyer
Jansky bielschowsky
Santavuori-haltia
What is the treatment for Batten disease type 2?
Cerliponase alfa
What is accumulated in mucopolysaccharidoses?
Glycosaminoglycans
Stored in the lysosomes in the brain, heart, cord, bone, connective tissue
Hunter or hurler?
- Sharp eyes
- Less mentally retarded
- Gargoyle face
- Hepatosplenomegaly
- Hunter
- Hunter
- Hurler
- BOTH due accumulation in dermatan and heparan sulfate
Which mucopolysaccharidoses in childhood is
NOT mentally retarded?
Morquio’s (MPS 4) and Maroteaux-Lamy (MPS 6)
Niemann pick/ Gaucher/ Tay Sach’s
- With CNS sxs, cherry red spot and hepatosplenomegaly
- With CNS sxs, cherry red spot NO hepatosplenomegaly
- NO CNS sxs, cherry red spot WITH hepatosplenomegaly
- Niemann pick
- Tay sach’s
- Gaucher’s disease
Which MPS has the least somatic changes, with mild MR and short stature? Hepatosplenomegaly is also present
San flippo causing heparan sulfate accumulation
What is the treatment for Hurler’s, MPS Type 1? L iduronidase is lost this condition
Laronidase or bone marrow stem cell transplantation
ALL MPS are inherited autosomal recessive EXCEPT FOR:
Hunter’s X linked
What MPS is characterized by DWARFISM AND OSTEOPEROSIS?
Morquio MPS 4
What diagnosis: pendular nystagmus, bird head dwarfism, leukodystrophy and nystagmus both invariable findings like pelizaeus merzbacher disease, peripheral nerve segmental demyelination and photosensitivity ? This condition also has retinitis pigmentosa and photosensitivity of the skin
Cockayne syndrome
What skeletal abnormality do ALL mucopolysaccharidoses possess?
Beaked thoracolumbar vertebrae
Myoclonic jerks and chorea and said to due to white matter or gray matter diseases?
Gray
Opsoclonus myoclunus sydnrome is classically described in which tumor of childhood?
Neuroblastoma
Re: Familial Progressive Myoclonus:
What is the usual course of lafora body (basophilic cytoplasmic bodies) polymyoclonus with epilepsy?
LB in dentate, brainstem and thalamus
Start between 11 to 18 years old then has focal occpital seizures THEN stimulus myoclonus and seizures start. Becomes bed bound dies from infection by 25
Re: Familial Progressive Myoclonus:
What are the ophthalmic findings in retina of juvenile batten disease? Autosomal recessive aka Spielmeyer disease
Yellow-gray areas of degeneration –> bone corpuscular shapes of retinitis pigmentosa –> visual loss
What are the 3 salient features of juvenile batten?
Visual impairment –> generalized seizures –> myoclonus
Then intellectual deterioration follows then cerebellar symptoms
What is AKA as late juvenile and adult ceroid lipofuscinosis that presents with a dementing illness or personality change in a young patient progressing to myoclnic seizures and cerebellar signs?
Kufs-Parry or Kufs disease
What is the ONE pathognomonic sign of Wilson disease/ westphal strümpell pseudosclerosis?
Kayser Fleischer rings
Re: Wilson disease
- What is the level of serum ceruloplasmin? serum copper? urinary copper?
- What was the first chelating agent used?
- 2 disturbances in copper metabolism?
- Inheritance pattern
- What is the level of serum ceruloplasmin? LOW: less than 20mg per dl
Low serum copper
High excretion more than 100mg Cu/ 24 hours - What was the fist chelating agent used? BAL British anti-Lewisite
- 2 disturbances in copper metabolism? Reduced rate of incorporation of copper into ceruloplasmin and reduction in in biliary copper excretion
- AR
What are the key clinical features of Wilson disease?
- Initial event: deposition of copper in the liver– acute or chronic encephalopathy: At this time NO KF YET
- Oropharyngeal: dysphagia, dysarthria– mouth held agape with a vacuous smile
- Parkinsonian syndrome
- Wing beating tremor movement
- Slowed saccades and limited upgaze
What is the most involved area in the brain for Wilson disease patients?
Putamen
What cells are hyperplastic in Wilson disease brains?
Alzheimer type 2 cells (protoplasmic astrocytes)
What are the treatment strategies for Wilson’s disease?
- Reduced dietary Cu to less than 1mg/day (avoid liver, mushrooms, cocoa, chocolate, nuts and shellfish)
- D-penicillamine 1 to 3g per day along iwth pyridoxine to avoid anemia
- Zinc acetate blocks the intestinal absorption of copper
What is the new name of Hallevorden-Spatz Disease? PANK mutation
Neurodegeneration with brain iron accumulation
What are the three signs and sxs characteristic of hallevorden-spatz?
Corticospinal: Spasticity, hyperreflexia, Babinski
Extrapyramidal: Rigidity, dystonia, choreoathetosis
Deterioration of intellect
What is the characteristic sign of Hallevorden spatz on MRI?
Eye of the tiger sign: Rim of the pallidum with intense black iron deposition with a small white area in its medial part that represents a zone of necrosis – T2 MRI!
What disease is described by HPRT1 mutation:
X-linked recessive choreoathetosis
Self mutiliation
Hyperuricemia
Lesch nyhan syndrome
What accumulates in the brains of persons with X-linked adrenoleukodystrophy?
Very long chain fatty acids
How does adrenoleukodystrophy present in female carriers?
Adrenoleukodystrophy aka sudanophilic leukodystrophy is a combination of what 2 disease processes?
Adrenomyeloneuropathy– spastic paraparesis–may look like MS found in heterozygous female carriers 10% of cases
Leukodystrophy and addisonian disease
What is the most common clinical picture for adrenoleukodystrophy?
Why is there bronzing of skin in this disease?
Degeneration of cerebral white matter in young males often with cortical blindness in 50% of the cases
High ACTH coming from the pituitary trying to stimulate a pathologic adrenal gland.
What are the two treatments for adrenoleukodystrophy?
Bone marrow transplant and diet high in mono unsaturated fatty acids
The body habitus of homocystinuria patients are similar to _________ disease but differ with respect to what neurologic abnormality?
Marfan disease
H patients have mental retardation
H also causes thromboembolic strokes because of thickening of brain, coronary and renal arteries.
What is also known as angiokeratoma corporis diffusum?
Fabry disease
What is the initial sign of Fabry disease? The disease affects the blood vessels: brain, kidney, viscera because of ceramide trihexose accummulation
Dermatologic manifestations?
How is it inherited?
Pain in the extremities– evocation by fever, hot weather, vigorous exercise
The disease is also known as angiokeratoma corporis diffusum– angiokeratomas are periumbilical that obliterate slightly with pressure
X-linked
What cases metablic disease of adolescecne can cause perosonality change and alteration in behavior?
- Wilson disease
- Adrenoleukodystrophy
- Metachromatic leukodystrophy
- Hallevorden-Spatz
- Kufs
- Lafora
- Tay sachs
What is another name for megaconial and pleoconial mitochondrial myopathy?
Ragged red fibers due to the subsarcolemmal and intermyofibrillar collections of membranous mitochondrial material in the type 1 red muscle fibers
What is mitochondrial disease is also known as a subacute necrotizing encephalomyelopathy?
Leigh disease
What are the 5 major categories of mitochondrial disorders? Which of them have ragged red fibers and lactic acidosis
- Ragged red fiber polymyopathy
- Progressive external ophthalmoplegia/ Kearns Sayre variants
- Leigh syndrome, fatal lactic acidosis, neuropathy with proximanl weakness ataxia and retinitis pigmentosa
- Myoclonic epilepsy and ragged red fibers in muscle (MERFF)
- Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS)
- Leber optic neuropathy
- Myoneural gastrointestinal encephalopathy
- Ragged red fiber polymyopathy + -
- Progressive external ophthalmoplegia/ Kearns Sayre variants: - -
- Leigh syndrome, fatal lactic acidosis, neuropathy with proximanl weakness ataxia and retinitis pigmentosa - +
- Myoclonic epilepsy and ragged red fibers + +
- Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS) ++
- Leber optic neuropathy - -
- Myoneural gastrointestinal encephalopathy + -
How to differentiate progressive external ophthalmoplegia/ Kearns-Sayre syndrome from myasthenia gravis?
PEO is NOT fatiguable and or responsive to cholinergic medications
What pathologic changes can be seen in Leigh disease? Aka subacute necrotizing encephalomyelopathy
Bilaterally symmetrical foci of spongy necrosis with myelin degeneration, vascular proliferation and gliosis in the thalami, midbrain, pons, medulla and spinal cord.
What is the NARP syndrome?
Neuropathy ataxia, retinitis pigmentosa
Defective ATPAase 6 of complex 5 of the mitochondrial respiratory chain
What is MERRF?
Myoclonic epilepsy with ragged red fibers
Usually presenting in childhood as myoclonus by startle or voluntary movement of the limbs
What is MELAS?
Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes
What imaging findings can be seen in MELAS?
Focal seizures heralding a stroke with radiographic pattern of infarction involving the cortex and immediate subcortical matter WITH BASAL GANGLIA CALCIFICATION
What is the kearns sayre syndrome?
The three primary findings in KSS are progressive paralysis of certain eye muscles (chronic progressive external ophthalmoplegia [CPEO]); abnormal accumulation of colored (pigmented) material on the nerve-rich membrane lining the eyes (atypical retinitis pigmentosa), leading to chronic inflammation, progressive degeneration, and wearing-away of certain eye structures (pigmentary degeneration of the retina); and heart disease (cardiomyopathy) such as heart block. Symptoms of this disorder are usually apparent before the age of 20 years.
Which among the leukodystrophies are linked to Jewish population?
Tay sachs and Niemann pick
