Metabolic Diseases Flashcards
1
Q
Urea Cycle Disorders
A
Complete absence - neonatal period with coma and hyperammonemia; respiratory alkalosis due to tachypnea
Partial absence - hyperammonemia with illness and stress
Both - normal glucose and not acidotic
2
Q
Abetalipoproteinemia/Bassen-Kornzweig Syndrome
A
- Autosomal Recessive
- Deficiency of microsomal triglyceride transfer protein (MTP) on chromosome 4 –> near absence of apo-B containing lipoproteins
- Affects posterior columns and spinocerebellar tracts (Ataxia, neuropathy, steatorrhea, retinitis pigmentosa, acanthocytosis)
- Loss of fat soluble vitamins
3
Q
Acid Maltase Deficiency/Pompes Disease - Infantile
A
- Neonatal hypotonia
- Macroglossia, cardiomegaly, hepatomegaly
- Membrane bound vacuoles are PAS +
- Usually die by 2 years of age (cardiorespiratory failure
4
Q
Acid Maltase Deficiency/Pompes Disease - Adult
A
- Presents in 20’s - 30’s
- Younger adults: fatigue
- Older adults: leg and trunk weakness
- Increased CK and myotonia of the paraspinal muscles on EMG
- Intracranial aneurysms due to glycogen depletion
5
Q
Acute Intermittent Porphyria
A
- Autosomal dominant
- Deficiency of porphobilinogen deaminase
- Onset in early adulthood
- Triggered by medications, fasting, infection hormonal changes
- Symptoms: severe abdominal pain, fever, tachycardia, HTN
- Weakness secondary to a motor neuropathy; can progress to quadriparesis and respiratory failure
- CNS symptoms: confusion, delirium, seizures, psychosis
- Tx: IV dextrose and propanolol
6
Q
Aromatic L-Amino Acid Decarboxylase Deficiency (AADC)
A
- Autosomal Recessive
- AADC is important in the synthesis of dopamine and serotonin
- Presents in the first few months of life
- Symptoms: dystonia, athetosis, tongue thrusting, torticollis, oculogyric crisis, ptosis, autonomic dysfunction (apnea, hypothermia, sweating)
- Ataxia can be seen later
7
Q
Neonatal Adrenoleukodystrophy
A
- AR
- Presents in the first few months
- Symptoms: dysmorphic, weak, hypotonic. Feed poorly. Seizures, hepatomegaly, retinal degeneration, hearing deficit
- Very long fatty chain acids are elevated
8
Q
Adrenoleukodystrophy - Overall
A
- X-linked recessive
- Mutations in ABCD1 on Xq28 - encodes ATP binding cassette protein
9
Q
Childhood Adrenoleukodystrophy
A
- 4-8 years old
- Behavioral problems and difficulty in school
- May appear to have ADHD
- Speech and handwriting deteriorate
- Problems with spatial orientation and auditory discrimination
- Seizures, spastic quadriparesis, dysphagia, vision loss
- Bronze skin
- MRI: first shows occipital demyelination –> spreads forward
- Lamellar cytoplasmic inclusions
- Tx: Bone marrow transplant
10
Q
Alexander Disease
A
- AD
- Mutation in GFAP
- Infantile form can present in first weeks of life
- Megalencephaly, seizures, progressive spastic quadriparesis
- MRI shows demyelination - particularly frontal
- Involves U fibers (along with Canavans)
- Rosenthal fibers found in astrocytes
11
Q
Ataxia with Vitamin E deficiency
A
- AR
- Friedreich-LIKE ataxia
- Mutation in alpha-tocopherol transfer protein (ATTP) on chromosome 8q
- Begins in puberty
- Progressive ataxia, loss of proprioception, areflexia, upgoing toes, titubation, deafness, tendon xanthomas, retinitis pigmentosa
12
Q
Canavan Disease
A
- AR - spongy degeneration of white matter
- Deficiency of aspartoacylase
- Sx start around 2 months
- Sx: hypotonia, regression, seizures, optic atrophy, macrocephaly
- Tone increases and late in course: spasticity, opisthotonus, posturing
- N-acetylaspartic acid is increased in the plasma and urine
- MRI: diffuse degeneration of white matter
13
Q
Carbohydrate-Deficient Glycoprotein
A
- Defect in PMM2
- Inverted nipples and abnormal fat distribution
- Neuro sx: strabismus, delay, cerebellar hypoplasia
- Systemic sx: coagulopathy, liver failure, pericardial effusion, nephrotic syndrome, renal cysts
- Children: seizures or stroke-like episodes
- Adults: MR and hypogonadism
14
Q
Cerebral Folate Deficiency
A
- 4 months of age with irritability and sleep issues
- Later, psychomotor retardation with cerebellar ataxia, dyskinesia, spastic paraplegia and sometimes seizures
- 3 years: Vision disturbances
- 6 years: Hearing loss
- CSF: Low 5-methyltetrahydrofolate
- Tx: Folinic acid (Leucovorin)
- Many patients have antibodies to folate receptors found on the choroid plexus
15
Q
Cerebrotendinous Xanthomatosis
A
- AR
- Mutation in sterol 27-hydroxylase gene on chromosome 2
- Increased cholestanol in plasma and tissues
- Sx: cataracts, xanthomas, ataxia, dementia; neonatal cholestatic jaundice and diarrhea
- Diffuse white matter abnormalities
- CT: hyperdense nodules in the cerebellum
- Tx: chenodeoxycholic acid
