Tegay - Pulmonary + Gastro

1 Primary Pulmonary hypolpasia

• extrmely rare

Secondary Pumonary Hypolasia

• way mroe common than primary

• caudes by

  • inadequate amontic fluid (olgiohydaminos)

  • inadequate respitry excursion

  • Inadaqute throaic volume (ribcage to small or another space occupying lesion: large mass, herniation of the bowl into chet cavity)

Oligiohydraminos

Potters Sequence: a result of lack of ammonitic fluid (oligohydramnios)

• Squished face, lack of movement, pulmonary hyposlaisa

Called Potter syndrome: if this is caused by bilateral renal agenesis

Causes for olgiohydramonis VARY

Obstructive Uropathy Sequence

Prune belly syndrome

• Obstructive uropathy: the urethra is obstructed, kidneys are working—> Bladder obstrution—> bladder deistnetion

• Potters sequence also often present

Spinal Muscualr Atrophay SMA type 0

Inadequate fetal respiration

• prenatal onsent

• decreased fetalmovmelnn, polyhyrominao, plmonary hypolasia,

• LETHAL AT BIRTH OR SHORTLY THEREAFTER

Inheritance: Autosomal Recessive (25% recurrence risk)

Congential Diagrammatic Hernia

Bowel herniation through a diaphragmatic defect

• Lungs have no space to devleop, the bowel physical limits

Mostly chromosomal anuplody, microdeltion/duplication

Often lethal, 50-80% surival rate but with stunted lungs (Pulmonary HTN/Insufficney)

Can be corrected with Tracheal Banding

Isoalted throaci Dystrophies

• Jarcho-Levin Syndrome: “short” ribcage

  • Autosomal recessiveL DLL3

• Jeune’s Asphixating Throaic Dystrophy” “skinny” ribcage

Generalized Skeletal Dysplasias

Thanatophoirc Dysplasia

• narrow thorax: severe Pulmonary hypoplasia (early death)

• type 1: short curved limbs (telephone receiver)

• type 2: shore straight limbs; large clover-leaf head

Autosomal DomiantL FGFR-3 Gene mutation

• Almost always DE NOVO MUTATION (no reproductive fitness, early death)

• Recurrence risk <5% (high rate of germline mosicam in mothers)—> recomend future testing in prgecines for parents with a child

Congenital Alveolar Capillary Dysplasia

Vascularization Disorder

• Preseistent hypoexmi in normal appering newborn: Cappillaries are not ‘hooked up” to avelor sacs—> cannot oxygenate

• ALWAYS LETHAL: only diaognesd at autopsy

Autosomal Domiant: FOXF1 mutaiton/dletion

• recurrence very rare

Surfactant Metabolism Disorder

Lack of functional surfactant: does not maintain the integrity of the alveolar

• in utero fine:

• at birth, alveoli collapse

• Lung transplast

Autosomal Recessive Surfactant Protien

Primary Ciliary Dyskinesia

The failure of cilia to move properly:

• Chronic Sino-pulmonary infection leading to Bronchiectasis

• Infertility, Hearing impairment

• Situs-Inversus ~50% (Kartagener’s Syndrome)

Autosomal Recessive Mutation of Ciliary genes (over 30 known)

Cystic Fibrosis

Classical clinical tried:

• chronic sino-plumonary infection

• Exocrine pancreatic insufficiency

• Elevated Sweat chloride and Sodium levels

Sodium-Chloride transport issues, mutations in CF Transmembrane conductor Regulator (CFTR) → Causes High thick sodium secretions

• Autosomal Recessive: most common mutation DelatF508 (Caucasian)

• PAN ETHNIC

Diagnosis: ( immno testing)

Alpha-1 A trisnpan

AAT Deficney is the major genetic cause of Chronic Obstructive Pulmonary Disease (COPD)→ An Expiratory Issue, irreversible

• AAT protease inhibtor: anti-trypsin deficieny—> unregulated protease (neutirphils) activity—> early emphysematous COPD (Damage

Autosomal Recessive inheritance: SERPINA1 gene mutation

• Higher incidence in caucasian

CF Newborn Screening

• Primary: IRT

• Secondary: DNA Screen

  • Expanded screening: 97 CFTR genes

  • A bit mute now: WGS allows for total picture and sequcing

• Confirmatoyr Testing: DNA sequecing and Sweat testing

Recurrence Risks for an affect child

25% for two carriers

( s )

CF Clinical issues

• Lungs: colonization by abnormal bacterial P Aerugionas, etc

  • Obstructive, restric pulmonary diease

• GI Manfiastions (Pacnrease): Pancrease is blocked up

  • Pancreatic insufficney: Malabsorption

  • Heptic Dysfunction

• Male Infertility: CFTR deficney = blocked vas deferens → sperm is fine but it cannot get into the semen

CF Treatment

• Nutrition

• Mechanical therpay

• Medication: Muscoltyics, Bronchodilators

  • Kalydeco (Ivacaftor) : CFTER Poentiator

  • Lumacaftor (Orkambi) : CFTR modulator

AAT Deficeiny Diagnosis

Alpha 1 Antitrypsin Serum Levels: Normal is >80mg/dl (false positive if measured during acute illness/stress)

AAT Protieace Inhibotr (Pi) phenotyping: eltroperhsis bands (M medium migration, S slow migration, Z very slow)

• Pi ZZ: most common diease phenotype: misfolded→ major protien dysfunction

• Pi MZ: most common carier phenotype: mild dysfunction

• Null: no bands present on eltropahis

SERPNA1 GENE

AAT Deficeny Cardinal Features

• COPD: 30-45yo, very early on

• Hepatitis/Cirrohis: 40-50yo ZZ Pi phenotype, protiens misfolded and gets stuck in the liver causing issues (need lvier transplant)

Empahsema in a non smoker

Liver Diease in a young person

When to Test for AAT?

( FILL IN FROM SLIDES)

AAT Deficiency Treatments

• COPD Monitoring and Treatment

• Liver transplant

Therapeutics have not really been developed

Intravenous infusion of purified pooled human serum AAT:

Hereditary Hemochromatosis (HH)

• Very common

  Clincial features

  • Increased Iorn uptake and Accumulation of iorn: it tends to depsoit in certain tissues, skin, heart, glands liver

  • Classic Triad of symptoms:

    • Glycosocuria

    • Cirrhosis

    • Bronzing of the skin

• Autosomal Inheritinace:

  • Mutation in HFE gene:

• Seen more in CAUCASIANS

• AGE OF ONSET VARIABLE (majority remain asymptomatic)

  • Male: 40-60yo,

  • FemaleL Post-Menopausal (menstration protects against iron overload)

Untreated HPE

• Artheritis

• Gladular dysfunction

• Liver Dysfunction

• Cardiac Dysfunction

• Progressively increased skin pigmenation

Diagonsis HFE-HH

Confirmatory Testing

HFE gene Mutation Analysis

• C282y/C282Y in >80% if Causcasins

• C282Y/H63D in 3-8% (not as severe)

• H63d/H63D: Carriers, not typtically clincally affected

But there are MANT other forms

NON-HFE HH

• Type 2: HH: Juvenlie HH

  • aurosomal recssive:

    • type2A (HJV gene, in 90%)

    • type2B (HAMP gene, in 10%)

• Type 3 HH: ( ss )

Treating HFE-HH

• Chelating

• Plhemobolating (bleeding)

• Avoid Iorn, Vitamin C, raw shellfish

Wilsons Disease

Failure of copper transport: excess copper deposit in tissues

• Liver, Brain, Eyes are affected by copper

  Autosomal Recessive: ATP7B Loss of Function mutation that transports copper:

Wilsons Diease Presentation

• Liver Disease: unexplained liver dysfunction,

• Neurologic disease: Movement disorder (unusual movements)

• Psychiatric symptoms: depression, neurotic behavior

• Kayser-Fleischer rings: copper deposits in the Cornea (A BOARDS QUESTION!!!!!) 50-90%

• Age of Onset: 3 to 60 years old (Kids or adults)

Wilsons Disease Treaments

• Copper chelation (increase urinary copper excretion)

Hereditary Pancreatitis

Inflammation of the Pancreas

Can be acute or chronic

can be genetic and non-genetic

• PRSS1 Gene Most common genetic cause: Autosomal Dominant

• SPINK1 Autosomal recessive

• CFTR Gene: Autosomal recessive, can present with recurrent pancreatitis

Hereditary Pancreatitis

• Prevention: low fat diet, small meals, good hydration, no alchol