Clinical Application/Correlation Week 2 Flashcards
G6PD Deficiency Key Clinical Features
- Jaundice
- Scleral icterus
- hemoglobinuria
- back pain
- intrinsic hemolysis after stressor
- RBC with Heinz body and bite cells
G6PD deficiency epidemiology
- most common enzyme deficiency worldwide
- asymptomatic until stressor
- x-linked recessive
- men affected, women carriers
- Middle Eastern, African, Asian descent
- provides protection against uncomplicated malaria
G6PD deficiency basic science
- G6PD is the rate limiting enzyme in pentose phosphate pathway
- reduces NADP to NADPH
- key part of oxidative stress pathway in RBC
- caused by heat, meds, infections, etc
- RBC have limited repair ability once mature (no nucleus)
G6PD deficiency key history and physical
Newborns
- neonatal jaundice/kernicterus
- lethargy
- poor muscle tone
- excessive sleepiness
- siblings with jaundice <24 hours of age
- bilirubin >95%
Adults
- pallor
- jaundice
- fatigue
- splenomegaly
- dark urine
- recent medication use
G6PD deficiency treatment
Management of neonatal jaundice
- phototherapy
- exchange transfusion
children/adults
- supportive care
- withdraw trigger meds
- transfusions
Hereditary Fructose Deficiency key clinical features
infant with vomiting after intro of fructose or sucrose
hepatomegaly
lactic acidosis
failure to thrive
hereditary fructose deficiency epidemiology
autosomal recessive
presents in infancy with introduction of new sugars
Hereditary Fructose Deficiency basic science
Lack aldolose B
patients cannot break down fructose-1 phosphate → toxic buildup
→ depletes phosphorous stores and decreases glycogenolysis → liver/renal failure
Hereditary fructose deficiency key history/physical exam
- young child (3-6 months)
- failure to thrive
- abdominal pain
- nausea/vomiting
- lethargy
- hypoglycemia
- enlarged liver
hereditary fructose deficiency diagnosis
amino acid/urine studies
metabolic abnormalities suggestive of disease
- hypoglycemia
- lactic acidema
- hypophosphatemia
- hyperuricemia
- hypermagnesemia
- hyperalanemia
hereditary fructose deficiency therapy/treatment
- immediate infusion of IV dextrose
- patients com in hypoglycemic
- correct metabolic derangements during initial/subsequent episodes
- avoid fracture/sucrose/sorbitol containing foods
- multivitamin supplements
- medication/vaccination review for potential toxicity
Lactase deficiency key clinical features
adolescent with GI complaints after lactose ingestion
bloating
flatulence
diarrhea
cramps
lactase deficiency epidemiology
75% of world’s population
male = female
most common asian, african, south american
types:
- primary
- secondary
- congenital
- developmental
lactase deficiency basic science
lactase: found in brush border of intestines
missing enzyme → increase in unabsorbed lactose in lumen
osmotic diarrhea - solute pulls water into intestines
gas production - from bacterial breakdown
lactase deficiency key history/physical
abdominal pain
nausea
vomiting
flatulence
bloating
diarrhea
borborygmi: loud gut noises
lactase deficiency dx/treatment
Ddx: IBS, Crohn’s, Celiac
Diagnosis:
- hydrogen breath test
- stool acidity test
- lower pH in lactase deficiency
- dietary elimination
- milk/lactose tolerance test
- biopsy- very rare
Treatment:
- avoid lactose containing products
- lactase supplements
- calcium and vitamin D supplements
Tay-Sachs mnemonic (SACHS TAY)
S pot in macula
A shkenazic Jew
C NS degredation
H ex A deficiency
S torage disease
T esting recommended
A utosomal recessive
Y oung death
Tay Sachs key features
developmental regression starting 3-6 months (born normal)
incoordination
hypotonia
hypereflexia
hyperacusis
cherry red spot in macula
tay-sachs epidemiology
autosomal recessive
very rare
Ashkenazi Jew, Cajun, Quebec, Irish, Amish
3 subtypes: infantile (most common), juvenile, late-onset
Tay-Sachs basic science
Hexoaminidase deficiency → accumulation of GM 3 Ganglioside in nerve cells
causes dysfunction then death of cells in CNS
Tay-Sachs key history/physical exam
average age of onset: 3-6. months
exaggerated startle response
blind by 30 months
seizures, irritability, screaming
macrocephaly
unresponsive by 2-3 years with death soon after
Tay-Sachs diagnosis
measurement of hexoaminidase level in blood (low)
MRI/CT changes
molecular genetics
Tay-Sachs treatment
- symptom management
- seizure control
- hydration/nutrition/airway management
- novel therapy
- enzyme replacement
Neimann-Pick Disease key features
cherry red spot
hepatomegaly and jaundice
progressive neurodegeneration
failure to thrive
hypotonia
Neimann-Pick disease epidemiology
3 types (A, B, C)
more common than Tay-Sacks
autosomal recessive
Ashkenazi Jew, Quebec
Neimann-Pick disease key history/physical
normal at birth
hepatomegaly +/- jaundice by three months
mild hypotonia at 6 months with rapid deterioration
developmental plateau at 12 months
many die by 2-3 years
cherry red spot on macula
failure to thrive
pancytopenia/bruising
Neimann-Pick Disease Diagnosis
clinical diagnosis
biomarkers
skin biopsy for genetic testing
Neimann-Pick disease treatment
most directed at symptomatic therapy
Miglustat may provide benefit at slowing progression of symptoms
several investigational therapies under study
