LEC 41 & 42 Flashcards
Define the term Inborn Error of Metabolism Discuss the pathogenic mechanisms observed with blocks in metabolic pathways Describe the genetic basis of enzyme deficiencies Recognize key clinical features of IBEMs Apply the knowledge of IBEM pathogenesis to the specific example of PKU. Discuss the importance of long-term follow up of patients with IBEMs Describe the diagnostic yield of newborn screening
What are Type 1 IEMs?
- Disorders of intermediary metabolism (sm molecules)
- Disorders resulting in acute/progressive intoxication from accumulation of toxic compounds proximal to metabolic block (PKU, Hereditary Fructose Intolerance, Urea Cycle Defects, MSUD)
These disorders are TREATABLE (ie: special diet)
What are Type 2 IEMs?
Disorders of energy metabolism
* features due at least in part to deficient energy production/utilization within tissue/organs (Mitochondrial respiratory chain disorders, Disorders of glycolysis, fatty acid oxidation disorders)
What are Type 3 IEMs?
- Disorders involving Complex Molecules
- Diseases involving cellular organelles that disturb synthesis or catabolism of complex molecules (Lysosomal storage diseases, peroxisomal diseases)
What is Neu-Laxova syndrome?
Serine synthesis defect (nonessential compound)
* severe fetal growth
* microcephaly
* distinct facial appearance
* Ichthyosis (scaly “fish” skin)
* Skeletal abnormalities
* perinatal lethality
Treat w/ serine supplementation
What is Menkes disease?
Copper transporter disease (metal transport defect)
* alopecia
* steely hair (steel wool)
* rare eyebrows
* sagging cheeks
* hypopigmentation
* pili torti
* trichorrexis nodosa
* hypotonia, hypothermia
What is the Keyser-Fleisher ring?
a deep copper-colored ring at the periphery of the cornea which is frequently found in Wilson disease and is thought to represent copper deposits
What are the clinical manifestations of Smith-Lemli-Opitz (SLO)?
- “SLO face” consists of microcephaly, bitemporal narrowing, ptosis, short nasal root, anteverted nares, and small chin
- Cleft palate
- Polydactyly and syndactyly (2nd & 3rd toe fusion)
- Genital anomalies: hypospadias, cryptorchidism
- CNS anomalies: Microcephaly, holoprosencephaly, enlarged ventricles, absence of the corpus callosum
What enzyme is deficient in SLO?
3B-hydroxycholesterol-7-reductase
converts 7-dehydroxycholesterol to cholesterol
What 2 compounds must be collected from a free flowing vein with no tourniquet and kept on ice and analyzed immediately?
- Ammonia
- Lactate
What are the clinical manifestations of Zellweger syndrome?
- Hypotonia
- Poor feeding
- Very bad development
- Seizures
- Hepatic cysts with liver dysfunction
- Retinal dystrophy
- Sensorineural hearing loss
- Death often within first year of life
What are some characteristics & examples of mitochondrial diseases (IE of energy metabolism)?
defects in mito. or nuclear DNA
Characteristics: stroke, exercise intolerance, diabetes mellitus, cardiomyopathy
Examples: Leigh syndrome, Pyruvate Dehydrogenase deficiency
