Metabolic

Question 1

Fatty acid oxidation defects vs. Glycogen storage disease (Von Gierke Type I)

Answer 1

BOTH hypoglycemia and hepatomegaly.

Urine Ketones:

• none or low in FA oxidation
• high in glycogen storage disease

Presentation:

• FAO: usually precipitated by viral illness
• GSD: usually “prolonged fasting” or sleeping thru the night for the first time

Question 2

B6 is used to treat what disorder?

Answer 2

Homocystinuria

- B6 enhances activity of the deficient enzyme (cystathionine beta-synthase)

Question 3

Lesch Nyhan

Answer 3

Developmental delay, Decreased IQ
Dystonic movements
Hypotonia, Hyperreflexia
Vomiting 
SELF-MUTILATION

X-linked
Deficiency of HGPRT

Increased Uric acid
-> renal stones and CKD

Question 4

Smith-Lemli-Opitz Syndrome

Answer 4

Defect in cholesterol biosynthesis
Accumulation of toxic cholesterol precursors
Autosomal Recessive

SGA, lots of dysmorphic features with syndactyly of 2-3 toes, structural abnl of CNS, hypoplastic LH, GI and renal abnl.

Die by 18 months

Question 5

Tyrosinemia Type I (Hepatorenal Tyrosinemia)

Answer 5

• FTT
• hepatic failure (hepatomegaly with hepatoblastoma and liver failure)
• renal tubular acidosis
• rickets

Dx: urine succinylacetone level is high

Tx: NTBC (blocks tyrosine metabolism before the block)

Question 6

Menkes disease

Answer 6

KINKY HAIR
low iQ
collagen abnl

X-linked
Dysfunction of copper metabolism - low copper

Question 7

MPS: Hurler vs. Hunter

Answer 7

Lysosomal Storage disorder
- deficiency of lysosomal enzymes required for the degradation of mucopolysaccharides or glycosaminoglycans, which then lead to abnormal accumulation of heparan sulfate, dermatan sulfate, or keratan sulfate. These metabolites then accumulate in the brain, cornea, bones, heart, lungs, liver, and spleen.

Hurler

• AR, defect in alpha-L-iduronidase
• coarsened facial features, large tongues
• corneal clouding
• Macrocephaly and communicating hydrocephalus
• low IQ
• skeletal growth retardation and dysostosis multiplex and joint stiffness
• atlantoaxial subluxation
• prognosis related to CARDIAC involvement

Hunter:

• X-linked, BOYS
• NO CORNEAL CLOUDING
• milder MPS1

Question 8

Treatment of FAO defects

Answer 8

Hypoketotic hypoglycemia and Reye-like syndrome

Carbohydrates (IV Dex) + Carnitine (needed to move LCFA into the mitochondria)

Question 9

What disease is associated with subdural hematomas and retinal hemorrhages?

Answer 9

Glutaric Acidemia

- defect in catabolic pathway of lysine, hydroxylysine, tryptophan

Question 10

Essential amino acid substitution pairs

Answer 10

Phenylalanine by tyrosine

Methionine by cysteine

Question 11

Adrenoleukodystrophy

Answer 11

Peroxisomal Disorder of FA degradation
-> accumulation of Very Long Chain FA***
leading to CNS demyelination

Associated cortisol deficiency/addison’s
- you get hyperpigmentation

X-linked

Question 12

Developmental regression is a red flag for?

Answer 12

Inborn errors of metabolism associated with neurologic deterioration and intellectual disability

Sanfilippo syndrome = mucopolysaccharide disorder

• inability to degrade heparan sulfate
• progressive mental deterioration, coarse facial features, joint stiffness, mild hepatosplenomegaly

VS:
Newborn screening includes biotinidase def, maple syrup disease, phenylketonuria - all of which are treatable and present in early infancy.

Question 13

Tay Sachs

Answer 13

Tay-Sachs disease is an autosomal recessive metabolic disorder caused by hexosaminidase A deficiency, which Presents as a neurodegenerative disorder. After an initial period of normal development in early infancy, there is loss of motor skills, increased weakness, decreased alertness, and increased startle response between 3 and 6 months of age.

Physical examination findings of Tay-Sachs disease include a cherry-red spot of the fovea centralis of the macula of the retina, normal-sized liver and spleen, hyperreflexia, ankle clonus, and diffuse muscular hypotonia.

Diagnosis of Tay-Sachs disease relies on the demonstration of low to absent levels of β-hexosaminidase A enzymatic activity in the white blood cells, with normal to high levels of the β-hexosaminidase B isoenzyme.

Question 14

Familial Lipoprotein Lipase Deficiency

Answer 14

HyperTAG
Abd pain, Pancreatitis, HSM
Eruptive Cutaneous Xanthomata - crops of small yellow papules

Impaired chylomicron clearance -> TAG accumulation

TX: Restrict fat intake