In addition to MSUD, what two other organic acidemias are associated with branched chain AA’s?
Isovaleric acidemia (sweaty feet and a/w leucine deficiency) and Propionic acidemia (requires biotin as a cofactor and a/w isoleucine deficiency)
What has low orotic acid in urine?
CPS deficiency
What has high arginine and what is a systemic problem?
Arginase deficiency with spastic diplegia
What has very high plasma citrulline and what is a systemic problem?
Arginosuccinic acid synthetase deficiency with brittle hair
What is the one X-linked recessive disease that is frequently found in females?
OTC deficiency
Smith-Lemli-Optiz
- how is it inherited?
- how does it present?
- what is elevated?
- autosomal recessive
- cataracts, cleft palate, anteverted nostrils, 2,3 toe syndactyly, congenital pyloric stenosis, Hirschprung’s, undervirilization in males
- 7-dehydrocholesterol is elevated
Which ichthyosis are autosomal recessive
harlequin, CIE, and lamellar
Which ichthyosis are autosomal dominant
Epidermolytic hyperkeratosis and ichthyosis vulgaris
Achondroplasia
- how is inherited
- but actually inherited
- what is gene is a problem
- what are physical findings
- auto dominant
- but most are sporadic
- mutation is in FGFR3
- narrow foramen magnum (at risk for hydrocephalus), trident hand, lordosis, kyphosis, rhizomelia (and mesomelia)
Treacher-Collins
- physical findings
everything is small:
micrognathia, auricular deformities, conductive hearing loss, choanal atresia, colobomas
Homocystinuria
- what conversion cannot happen?
- what metabolites are elevated?
- physical findings?
- cardiac defects?
- Tx? What conversion happens with treatment?
- homocysteine cannot be converted into cystathione
- elevated homocysteine and methionine
- lens subluxation downward, osteoporosis, long fingers, pectus excavatum or carinatum, mental retardation
- thrombosis, medial degeneration of aorta and carotids
- Tx: B6, betaine - converts homocysteine back into methionine
Prader-Willi
- chromosome affected?
- what is the most common genetic mechanism?
- features during pregnancy?
- symptoms?
- diagnosis?
- chromosome 15
- deletion of paternal genes (uniparental disomy is second cause)
- during pregnancy: polyhydramnios and breech presentation
- bitemporal wasting, severe hypotonia, difficulty feeding, small mouth, almond shaped eyes, micropenis, undescended testes
- methylation study
What diseases are inherited by microdeletions?
DiGeorge, Prader-Willi, Angelman, NF, Williams, Rubenstein-Taybi, Wolf-Hirschhorn
What 3 diseases are inherited by problems of imprinting?
Angelman, Prader-Willi, and Beckwith-Weideman
What diseases have trinucleotide repeats?
Huntington’s (CAG), myotonic dystrophy (CTG), fragile X (CGG)
What is deficient in Menkes disease?
What are symptoms?
How is it inherited?
- copper transport
- brittle steely hair, sagging lips, abnormal bone and skin
- X-linked recessive
What are most T21 due to?
- What is not common?
- What is even less common?
95% from nondysjunction (47 chromosomes)
- 4% from unbalanced translocation (14-21); 1/4 of these are due to familial translocation
- 1% due to mosaicism and have milder disease
Three problems in Stickler syndrome
Pierre-Robin sequence, cataracts, hearing loss
Lowe’s
- how is inherited
- aka
- whats the problem?
- increased maternal ___?
The boy OCRR is beLOWE the bridge
- X-linked recessive
- oculocerebrorenal reproductive syndrome
- affects enzymatic function of golgi
- maternal AFP
Bartter’s
- hyponatremia, hypokalemia, hypercalciuria, metabolic alkalosis
- think lose all their salts - become hypotensive, dehydrated, need to replace sodium and potassium
von Gierke’s (type I glycogen storage disease)
- enzyme deficiency?
- three points
- deficiency in glucose-6-phosphatase
- high uric acid, high lactate, and liver failure
von gURICke’s
Noonan’s three things?
dysplastic pulmonary valve
chylothorax
cryptorchidism
What IEM should glucose NOT be given?
Pyruvate dehydrogenase
Primary fuel for muscles?
fat
