Metabolic disorders Flashcards
Case
CC: Poor weight Gain
K.A. 3mo/F , sees you for the first time with the chief complaint of
poor weight gain.
Pertinent in the birth history is history of
(+) feeding difficulties with frequent vomiting episodes
(+) prolonged jaundice
(+) poor weight gain
(+) history of seizures
Newborn screening: (+)
Nutritional History: Exclusively breastfed
PE:
Weight for age below -3 , Length for age below -3
lethargic , generalized hypotonia, (+) jaundice
(+) bilateral cataracts
(+) hepatomegaly
(+) splenomegaly
Laboratory:
CBC: WBC 9.0 Hgb 145 Hct .45 plt
Blood CS: NG5D
RBS: low
ABG: metabolic acidosis
Babygram: Normal chest, hepatomegaly, paucity of bowel pattern
What is the primary impression?
Galactosemia
What are the basis for the primary impression?
Basis:
Typical signs and Symptoms at Birth/ Hx
o feeding difficulties with frequent vomiting episodes
o prolonged jaundice
o poor weight gain
o history of seizures
o Newborn screening: (+)
Physical findings
o Poor growth within the first few weeks of life
o Jaundice
o Bleeding from coagulopathy
o Liver dysfunction and/or hepatomegaly
o Cataracts (sometimes as early as the first few days of
life)
o Lethargy
o Hypotonia
o Sepsis (E coli)
Lab Results:
o NBS (+) Galactosemia
o RBS: low
o ABG: metabolic acidosis
What are the differentials?
- Sepsis/ TORCH
Rule in:
Vomiting, poor feeding
Poor weight gain
seizures
Cataracts, Hepatosplenomegaly -
TORCH
Galactosemia patients are at
increased risk for E. coli sepsis
Rule out:
(+) NBS: Galactosemia
jaundice WBC normal, Blood CS: NG
- IEM
Rule in:
Vomiting, poor feeding
jaundice
Poor weight gain
seizures
ABG: metabolic acidosis
RBS: low
Rule out:
(+) NBS: Galactosemia
- GERD
Rule in: Vomiting, poor feeding (+)
Poor weight gain
Severely wasted, severe
stunted
Rule out:
NBS: Galactosemia
Jaundice, seizure
Cataracts, hepatosplenomegaly
4.GI malformations: (Atresia, pyloric stenosis)
Rule in:
Vomiting, poor feeding
Poor weight gain
Severely wasted, severe
stunted
Rule out:
(+) NBS: Galactosemia
Jaundice, seizure
Cataracts, hepatosplenomegaly
Babygram: Paucity of gas bowel
patterns
- RTA
Rule in:
Vomiting, poor feeding
Poor weight gain
Severely wasted, severe
stunted
ABG: metabolic acidosis
Rule out:
(+) NBS: Galactosemia
Jaundice, seizure
Cataracts, hepatosplenomegaly
work-up
o A positive (ie, abnormal) indication on the newborn
screen must be followed by a Direct enzyme assay
using erythrocytes which shows Deficient activity of
galactose-1-phosphate uridyl transferase
demonstrable in hemolysates of erythrocytes, which
also exhibit increased concentrations of galactose-1-
phosphate
Additional in work up for cases of FTT:
o Basic work-up may include CBC (for anemia), Blood
gas (RTA, metabolic disease), TFTs, UA
o (renal and metabolic disease), ESR/CRP (sign of
inflammation/infection), stool for fat, pH, reducing
o substances, occult blood, ova and parasites, sweat
chloride, lead, TB and HIV.
Treatment
Treatment:
o Early diagnosis and treatment have improved the
prognosis of galactosemia
o Elimination of galactose from the diet reverses growth
failure and renal and hepatic dysfunction.
o Various milk substitutes are available (casein
hydrolysates, soybean-based formula).
Prognosis
Prognosis:
o Most patients with severe galactosemia who do not
receive treatment often do not survive the newborn
period. Even with appropriate dietary therapy, most
patients have at least 1-2 long-term complications
(ovarian failure with primary or secondary
amenorrhea, decreased bone mineral density,
developmental delay, and learning disabilities that
increase in severity with age
Acidic urine odor
Methylmalonic acidemia (methylmalonic acid)
Cabbage urine odor
hepatorenal tyrosinemia, methionine malabsorption
Cat urine
3-methylcrotonyl CoA dehydrogenase deficiency, multiple carboxylase deficiency
Maple syrup/burnt syrup
MSUD
mouse/musty
PKU (phenylacetate)
rancid butter
hepatorenal tyrosenemia
Sweaty feet
isovaleric acidemia, glutaric aciduria, Type II (Isovaleric acid)
Clinical approach to a newborn infant with a suspected metabolic disorder
p. 178
- Clues in Hx:
- Marriage is consanguineous, hx of recurrent abortion,
hx of unexplained neonatal death in siblings especially
assoc with acidosis, coma and convulsions, sibling
diagnosed suffering an IEM - Clues in PE
- Tachypnea, apnea, lethargy
- Hyper/hypotonicity
- Hepatosplenomegaly, ambiguous genitalia, jaundice
- Dysmorphic or coarse facial fx
- Rashes/patchy hypopigmentation
- Ocular (cataracts, lens dislocation, pigmentary
retinopathy
- Intracranial hemorrhage
- Unusual odors - Laboratory
a. ABG – metabolic acidosis with inc anion
gap, primary respiratory alkalosis
b. Plasma ammonia elev
c. Hgt – hypoglycemia
d. Serum and urine ketones – ketosis and
ketonuria
e. TB, DB, IB, elev LFTs – hyperbilirubinemia
f. Lactic acidosis
g. High lactate/pyruvate ratio
h. Non-glucose reducing substances in urine
i. CBC – neutropenia, thrombocytopenia
Management
Mgt
1. Newborn screening - do after the 24th HOL or 48th-72nd HOL. If collected at <24h, repeat at 2 WOL
- In sick children, no later than 7d; NICU test by 7d-1 mo.
- For PT, ideal time should be at 5-7d old
- Prior to providing TPN, blood transfusion or on NPO
- Newborn screening act 2004 or Republic act 9288
o Provide an opportunity for every NB for early identification of conditions that can cause mental retardation or death
What is the enzyme defect for congenital hypothyroidism?
multiple disorders
CM: appear normal at birth; large fontanelles, jaundice, macroglossia, hypotonic, lethargic, weak cry
What is the enzyme defect in CAH?
21-hydroxylase deficiency
CM: salt wasting
simple virilizing
What is the enzyme defect of phenylketonuria?
phenylalanine hydroxylase
PTPS
Normal at birth
What is the enzyme defect in galactosemia?
Galactose 1 phosphate
Uridyl transferase
Galactokinase
Galactose-4 epimerase
CM: normal at birth, jaundice, feeding intolerance, FTT, hepatomegaly
What is the enzyme defect in G6PD deficiency?
Glucose-6-phosphate dehydrogenase
CM: normal at birth; jaundice, pallor
Golden period
CH: 2 weeks
enzyme screened: TSH
Confirmatory: TSH and T4 levels
CAH:
1-2 weeks
enzyme screened: 17-OHP
Confirmatory: 17-OHP quantitative levels
PKU:
2 weeks
enzyme: Phenylalanine
Confirmatory:phenylalanine/tyrosine
Gal: 3 weeeks
enzyme screened: GALT/Gal metabolites
confirmatory: enzyme measurement
G6PD deficiency:
enzyme: G6PD
confirmatory: quantitative enzyme measurement
Factors that affect NBS result:
- BT, dialysis, IV abx, PT, NPO since birth
Differetials
DDx: G6PD deficiency (p.148)
Hypothyroidism (p.125)
Congenital adrenal hyperplasia (p.172)
