Remember the 3 large distinctions of anemia types and potential etiologies:
Microcytic (MCV < 80)
Normocytic (MCV 80-100)
Macrocytic (MCV >100)

Know how to interpret an iron panel in a medically ill patient:

1) Ignore the transferrin saturation

• Reason: does not discriminate between anemia of inflammation and iron deficiency

2) Assess ferritin

• <20: Iron deficiency
• 20-100: Iron deficiency likely if inflammation, chronic viral infection, etc.
• 100-800: Unlikely iron deficiency (unless hepatitis, chronic HD)
• >800: Extremely unlikely iron deficient

3)Assess the TIBC (preferred over transferrin level)

• >400: Iron deficient
• 300-400: Likely a component of iron deficiency
• 200-300: Unlikely iron deficient
• <200: Very unlikely iron deficient, usually inflammation, liver failure

Tuberous Sclerosis:

• Autosomal dominant genetic disorder due to a mutation in either TSC1 or TSC2 gene.
• Incidence of 1 in 5000-10000 live births
• De novo mutations account for ~ 80% of TSC cases
• TSC is highly variable in expression – thus the severity of disease can vary substantially among affected individuals within the same family
• TSC is characterized by the development of a variety of benign tumors in multiple organs: brain, heart, skin, kidney, lung, and liver

81-95% of TSC patients have on the characteristic skin lesions:

• Angiofibromas ~ typically on the malar region of the face
• Hypopigmented macules AKA ash-leaf spots ~ elliptic in shape
• Shagreen patches ~ usually over the lower trunk
• A distinctive brown fibrous plaque on the forehead ~ usually the first and most readily recognized feature of TSC
• Periungual/subungual fibromas develop during adolescence or adulthood; toenails > fingernails

CNS lesions characteristic of TSC include:

• Glioneuronal hamartomas (corticol tubers)
• Subependymal nodules
• Subependymals giant cell tumors (SGCTs): the characteristic brain tumor of TSC with a prevalence of ~ 5-20%, with 6-9% symptomatic

Neurological complications include:

• Seizures ~ 79-90% of patients, most often in the 1st year of life
• Cognitive deficits ~ 44-65%, associated with a history of infantile spasms or refractory seizures
• Behavioral problems ~ 40-90%; typically hyperactivity, inattention, and self-injury

Cardiovascular complications include:

• Rhabdomyoma: a benign tumor that often presents as multiple lesions
• No evidence for malignant transformation; no treatment is necessary for asymptomatic tumors
• Unlike other lesions of TSC, cardiac rhabdomyomas often disappear in later life spontaneously

Renal complications include:

• Angiomyolipomas ~ 55-75% (estimated incidence)
• Benign tumors composed of abnormal vessels, immature smooth-muscle cells, and fat cells
• Due to the abnormal vasculature and potential for aneurysms, spontaneously life-threatening bleeding is a potential complication

Pulmonary complication of TSC:

• Lympangiomyomatosis (LAM); Women (almost exclusively) – Widespread pulmonary proliferation of abnormal smooth-muscle cells and cystic changes within the lung parenchyma
• Two common intial manifestations of LAM: dyspnea and spontaneous pneumothroax

Diagnostic criteria for TSC:

Diagnosis is based on either genetic testing results and/or clinical findings

Genetic criteria:

• Identification of either a TSC1 or TSC2 pathogenic mutation (i.e. a mutation that clearly inactivates the function of TSC1/2 proteins)

Clinical criteria:

• 11 major and 6 minor features
• Definite diagnosis requires 2 major or 1 major/>2 minor features

Management of TSC:

• Requires a multidisciplinary approach of specialists including: neurologists, dermatologists, geneticists, and pulmonologists
• Referral to a TSC clinic is recommended given the complexity of the disease (next slide)
• Long-term follow-up including monitoring of lesion growth (angiomyolipomas and SGCTs); no conclusive guidelines exist
  • Standard practice: brain/abdominal imaging every 3 years; more frequently with known lesions
  • Genetic counseling for family planning (risk of affected child is 50%)

Therapeutic Options:

• Sirolimus (mTOR inhibitor) has been identified as a potential option given tumor cells from patients with TSC active mTOR (studies ongoing)