Metabolic Disorders Flashcards
Rett Syndrome
MECP-2
Females
Regression, severe intellectual disability
Arrested head growth
Central apnea and hyperventilation
Intractable epilepsy
Arrhythmias
Fragile X
Most common cause of intellectual disability
>5% of ASD in males
X linked triplet repeat (CGG)
>200 repeats on FMR1 Gene
Famhx of females with ovarian insufficiency
Male >50 yo w/ tremor
Can have progressive cerebellar ataxia
CGG repeat
Fragile X
CTG repeat
Myotonic dystrophy
CAG repeat
Kennedy’s disease (androgen receptor antibody)
SCA
Huntington’s disease
Dentatorubral-pallidouysian (DRPLA)
GCG repeat
Oculopharyngeal muscular dystrophy
15q11.2q.13.1 imprinting, deletion or uniparental disomy
Prader Willi
Angelman
15q11.2q.13.1 paternal copy absent
Prader Willi
15q11.2q.13.1 maternal copy absent
Angelman
Prader Willi Phenotype
Hypotonia and FTT in infancy
Rapid weight gain between 1-6 yo
Hyperphagia
Developmental delay
Hypogonadism
Small stature and small hands, almond shaped
Behavioral issues
Angelman Phenotype
Developmental delay
Severe ID
Seizure w/ 2-3 Hz high amplitude slow wave on EEG
Ataxia
Inappropriate happy demeanor (happy puppet)
Wide spaced teeth/prognathism
UBE3A gene
Angelman
Chromosome 5p deletion
Cru-di-chat syndrome
Cru-di-chat syndrome phenotype
Microcephaly, micrognathia, small hands
Severe ID, delays, poor feeding, drooling (laryngeal issues)
DiGeorge/Velocardiofacial chromosome
22q11.2 deletion
Symptoms of DiGeorge;
Cono-truncal malformation
Palatal abnormalities and velopharyngeal incompetence (VPI)
Immune deficiencies
Hypocalcemia
Learning disabilities, speech delay, seizures, hearing loss, behavioral disturbances
CATCH 22 of DiGeorge
Cardiac Abnormality, T-cell defect, Clefting, Hypocalcemia
Chromosomal abnormality for Williams Syndrome?
Chromosome 7q, includes gene encoding Elastin → connective tissue
Symptoms of Williams Symptoms:
Hypotonia, hyperflexible joints
Hypercalcemia
Cardiac: supravalvular aortic stenosis
X-linked dominant disorders:
Rett syndrome
Aicardi Syndrome
X-linked lissencephaly
Periventricular nodular heterotopia due to FIL-1 gene mutation
Fabry’s disease genetics and enzyme deficiency:
X-linked recessive
Deficiency of alpha galactosidase A
What are the symptoms of Fabry’s disease?
Recurrent attacks of burning pain in distal extremities (acroparesthesias) exacerbated with heat, fever and exercise
Autonomic instability
Cardiomyopathy, stroke, aneurysm, corneal deposits
Angiokeratomas
Farber’s enzyme deficiency:
Ceramidase
Sandhoff enzyme deficiency:
Hexosaminidase A and B
Niemann-Pick enzyme deficiency:
Sphingomyelinase
Gaucher enzyme deficiency:
Beta glucosidase
Krabbe enzyme deficiency:
Galactosylceramide beta galactosidase = galactocerebrosidase
Globoid cell (PAS +ve) in white matter
Metachromatic leukodystrophy enzyme deficiency:
Arylsulfatase A
Tay Sachs enzyme deficiency:
Hexosaminidase A
Characteristics of Faber’s disease:
Arthropathy and subcutaneous nodules
Cherry red spot
Diseases that will have Ashkenazi jews mentioned in the vignette;
Gaucher
Nieman Pick
Tay Sachs
Characteristics of Gaucher’s disease?
Gaucher cells→ histiocytes with lipids (PAS +ve)
Spasticity, seizures, rigidity, Hepatosplenomegaly
Gauchers type __ will generally die before age 2.
2
Characteristics of Gaucher’s disease?
Foamy histiocytes, jaundice and hepatomegaly
Tay Sachs Disease characteristics?
No visceral (foamy neurons)
Increased startle response
Death at 5 years
Sandhoff disease characteristics?
Mild hepatosplenomegaly
Pan-ethnic
Death at 3 years
Coarse granulation in histiocytes (sand)
What diseases present with a cherry red spot?
Farber
Sialidosis
GM1 gangliosidosis
Sandhoff
Tay-Sachs
Niemann Pick A
Krabbe disease, also known as ___
Globoid cell leukodystrophy
What are the symptoms of Krabbe disease?
Regression, blindness, hypotonia and deafness
Progressive demyelinating peripheral neuropathy → lost reflexes+Babinski
MRI findings of Krabbe disease:
FLAIR hyperintensity in basal ganglia, thalami, corona radiata, brainstem and cerebellum
What are the symptoms of cerebral folate deficiency?
Irritability, loss of vision, spasticity and hearing
Reduced 5-methyltetrahydrofolate. Treatable with folinic acid
If there is an arylsulfatase A deficiency, what does this cause?
Myelin breakdown
What are the types of Mucopolysaccharidosis?
(6 total, skip V)
I. Hurler
II. Hunter
III. Sanfilippo
IV. Morquio
VI. Maroteaux-Lamy
VII. Sly
Deficiency in Hurlers?
Alpha iduronidase
Deficiency in Hunters?
Iduronate sulfatase
Deficiency in Sanfilippo?
Heparan sulfate
Deficiency in Morquio?
Galactose-6-sulfatase (Keratan sulfate)
Deficiency in Maroteaux-Lamy?
N-acetylgalactosamine, arylsulfatase B (Dermatan sulfate)
Deficiency in Sly?
Hyaluronidase
All of the mucopolysaccharidosis are autosomal recessive except ____.
Hunter (which is also the only one without corneal clouding)
What are common features of mucopolysaccharidosis?
Coarse features and skeletal abnormalities (dysostosis multiplex)
Hepatomegaly, OSA, hearing loss
Zebra bodies in the lysosomes
Treatment for mucopolysaccharidosis:
Bone marrow transplant and enzyme replacement
Aminoacidopathies: Branched amino acids
Maple Syrup Urine Disease
Aminoacidopathies: Neutral amino acids
Hartnup disease (Niacin)
Aminoacidopathies: Sulfated amino acids
Molybdenum cofactor deficiency
Lens dislocation
Aminoacidopathies: Methionine metabolism
Homocystinuria
Aminoacidopathies: Glycine metabolism
Glycine encephalopathy (nonketotic hyperglycinemia)
Aminoacidopathies: Phenylalanine
Phenylketonuria
McArdle disease
Glycogen storage disease IV
Carnitine palmitoyl transferase deficiency I
Fatty acid oxidation defect
What are the periodic paralysis?
Hypokalemia
Hyperkalemia
Andersen Tawil syndrome
Metabolic diseases with macrocephaly
Glutaric aciduria type I
Tay Sachs disease
Alexander disease
Canavan disease
Metabolic diseases with skin rash
Abetalipoproteinemia
PKU
Biotinidase
Hartnup disease
Refsum disease
Fabry’s
Inheritance and genetics of Wilson’s disease:
Autosomal recessive (ATP7B)
Pathogenesis of Wilson’s disease:
Copper transportation defect from hepatocyte to bile
Symptoms of Wilson’s disease:
Liver failure
Psychiatric symptoms
Wing beating tremors
Kayser Fleischer rings
Sunflower cataract
MRI findings of Wilson’s disease:
Increased signal in superior colliculi, medial substantia nigra and tegmentum
Panda sign
What test can you do for Wilson’s disease and what would those show?
Copper -> decreased
Ceruloplasmin -> decreased
24 hr copper excretion -> increased
Treatment for Wilson’s disease:
Chelation
What is the pathogenesis of Menkes? And genetics?
Failure to absorb copper from GI
Copper transporting ATPase (ATP7A)
How does Menkes present?
Stimulation myoclonus, hypotonia, regression, poor feeding
Kinky hair, vasculopathy
Can look like child abuse
What test can you do for Menkes disease and what would those show?
Copper -> decreased
Ceruloplasmin -> decreased
24 hr copper excretion -> decreased
Treatment for Menkes:
Copper supplementation
What happens in Pantothenate Kinase-Associated Neurodegeneration (PKAN)?
Brain iron accumulation
Rigidity and movement disorders
Retinopathy
Globus pallidus increased signal (eye of the tiger)
What is the mutation found in PKAN?
Mutation of pantothenate kinase gene (PANK2)
