Genetics & metabolism Flashcards
Menke disease
vs.
Moubis dynrome
Twisted, fractured hair (kinky hair), wormian bones, cerebral deterioration, saggy lips, joint laxity. –> copper transport
x-link recessive.
Moubis: 6th, 7th cranial nerve palsy, mental deficiency.
Dwarfism: what gene and what inheritance pattern
FGFR3 mutation
Autosomal dominent
but A LOT de novo
Most inborn errors of metabolism follows what inheritance pattern
Give an exception
autosomal recessive.
Exception:
Ornithine carbamyl transferase (also most common)
(high urine orotic aice, high glutamine/alanine. low citrulline and arginine) –> Urea cycle defect
THIS IS X-Link Recessive
x-linked disorders among inborn errors of metabolism
OTC deficiency
X-linked ALD
Hunter Syndrome
x-linked, not inborn errors of metabolism:
incontinentia pigmenti
For each of the following group of disorder, give the basic presentation
- Fatty Acid Oxidation Disorders
- Organic Acidemia
- Aminoacidopathy
- Urea Cycle Disorders
- Fatty Acid Oxidation Disorders
Hypoketotic hypoglycemic - Organic Acidemias
Metabolic acidosis with anion gap - Aminoacidopahties
No acidosis or hyperammonemia - Urea Cycle Disorders
Hyperammonemia without acidosis.
Organic Acidemias
Metabolic acidosis with anion gap
Urine Ketone
plasma lactate is elevated in what
mitochondrial disease
glycogen storage disease 1 A
Plasma Amino Acids can help with what disorders?
PKU
MSUD
Urea Cycle Disorders
amino aciodpahties
Urine Organic Acids
helps diagnose what disorders
Mehtymalonic Acidemia
Propionic Acidemia
Isovaleric Acidemia
Organic Acidemia
Plasma Acylcarnitine and Carnitine can pick up a lot of disorders
Tandem Mass Spectroscopy is used for NBS
is OTC screened on NBS
no
(neither is cholesterol disorder)
PKU (Phenylketonuria)
This is amino and organic acidopathies.
autosomal recessive
metabolism of Phenylalanine (no phenylealanine hydroxylase -> classic type.
Hence: cannot convert from phenyalanine to Tyrosine.
mousy urine order or musty urine order.
elevated:
Phenyalanine
AND Phe/Tyr ratio
no symptoms in newborn period
if mom has PKU and cannot control diet, elevated phenylalanine is teratogenic (microcephaly, IUGR, intellectual disability, congenital heart disease)
MSUD
autosomal recessive
elevated Leucine, Valine, isoleucine.
(Leucine toxic to brain. )
branched chain ketoacid dehydrogenase deficiency.
> elevated ketones in urine
– Poor feeding, lethargy, coma, apnea.
Can present BEFORE NBS
maple odor.
Hypoglycemia and hyperammonemia UNUSUAL
very HIGH urine Ketone.
Transient Tyrosinemia of the Newborn
elevated Tyrosinemia but no succinylacetone in urine.
Type 1 tryosinemia is autosomal recessive and has succinylacetone in urine.
Nonketotic Hyperglycinemia
measure CSF/Plasma glycine
hiccups, seizure, myoclonus.
Propionic Acidemia
This is organic acidemia
Defect in propionyl CoA Carboxylase.
Autosomal recessive.
severe, lethargy, coma, neutropenia, thrombocytopenia.
METABOLIC ACIDOSIS, ANION GAP, HYPERAMMONEMIA
why carnitine for organic acidemias
Carnitine becomes covalently bound to the organic
acid and facilitates excretion in urine.
Carnitine needed for fatty acid oxidation of long chain fats
Methylmalonic Acidemia
AR
methylmalonylCoA Mutase
neonatal onset, lerthargy, coma
metabolic acidosis, anion gap
hyperammonemia, hyperglycinemia
neutropenia, thrombocytopenia,
Treatment: Diet, carnitine, B12,
if mom has vegan diet and low B12, baby will screen positive.
Ornithine Transcarbamylase Deficiency (OTC)
IMPORTANT
X-link
Male severe.
(female can have milder form)
classic urea cycle.
normal for 24-48 hours. then poor feeding, grunting, lethargy, coma, cerebral edema.
Orotic acid elevates in urine
Citrullinemia in Urea cycle defect
argininosuccinate synthase or argininosuccinit lyase deficiency.
Brittle hair, hyepr-ammonia
very high citrulline, orotic aciduria
need to supplement arginine.
Arginase deficiency -> Argininemia
AR,
can have neonatal hyperammonemia.
But often with Spastic Quadriplegia, delay milstone.
orotic aciduria.
How to tell difference between OTC deficiency and CPS deficiency
Orotic acid high –> OTC deficiency
Orotic Acid low (and low Citrulline) –> CPS deficiency
(carbamyl phosphatate synthase deficiency)
know slight 67-68 (genetic 1)
Neonate with liver failure: ddx
Tyrosinemia Type 1
Classic Galactosemia
HFI (Hereditary Fructose Intolerance)
Mucopolysaccharidosis I (MPS Type 1)
Lysosomal Storage Disease
Hurler, Hurler-Schei, Schei
autosomal recessive,
alpha-L-Iduronidase deficiency (cannot break down glycosaminoglycans)
normal at birth, but has coarse facial features, hepatosplenomegaly, dysostosis multiplex, corneal clouding.
which has corneal clouding
Hurler syndrome
NOT Hunter
Both are lysosomal storage disease
Myotonic Dystrophy
CGT repeat, and severity classification
22q11.2 Deletion
DiGeorge
Velocardiofacial syndrome
Conotruncal defect in DiGeorge
ToF, Interrupted aortic arch, +/- Truncus in Velocardiofacial syndrome.
Fanconie Anemia
Prenatal/postnatal short stature
Microcephaly
Hypoplastic
thumb/radius
GU anomalies
Hyper or
hypopigmentation
Eye anomalies
GU anomalies
AR (19 genes), AD (one gene), one X-linked.
Genomic instability syndrome associated with congenital abnortmalities, bone marrow failure, cancer predisoposition
can be associated with VACTERL (won’t test)
enzyme deficiency in Type I glycogen storage disease and Type II
Type I:
Glucose-6-Phosphatase
(liver, kidney, GI, metabolic acidosis and hypoglycemia)
Type II: Pompe
Lysosomal alpha-glucosidase
cardiomegaly, CNS.
hypoketotic, hypoglycemic crisis
fatty acid oxidation disorder
CPK and Uric acid are often elevated
cataract, hepatomegaly,
poorly breast feed baby
Dx
what enzyme deficient
Galactesemia
Galactose-1-phosphate uridyltransferase (GALT)
hypotonia, high forhead, flat orbital bridge, flate nasal bridge, hepatomegaly, calcifcation in poplteal area
zellweger syndrome
(cerebro-hepato-renal syndrome)
very long chain fatty acid accumulation
hepatic and renal peroxisome issue
