(FINAL) CC1 LEC L1.5 Aminoacidopathies & Protein Abnormalities

Phenylketonuria (PKU)

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • PAH (Phenylalanine hydroxylase) deficiency

• Hallmark Clinical Features & Odors

  • Mental retardation, microcephaly (in infants of untreated mothers).

Tyrosinemia Type 1

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • fumarylacetoacetate hydrolase (FAH)

• Hallmark Clinical Features & Odors

  • Cabbage-like odor, jaundice, liver failure, bleeding.

Tyrosinemia Type 2

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • Tyrosine Aminotransferase (TAT)

• Hallmark Clinical Features & Odors

  • Photophobia, eye/skin lesions.

Tyrosinemia Type 3

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • 4-hydroxyphenylpyruvate dioxygenase (HPD)

• Hallmark Clinical Features & Odors

  • Seizures, loss of balance.

Alkaptonuria

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • HGD gene (Homogentisate 1,2-dioxygenase)

• Hallmark Clinical Features & Odors

  • Ochronosis: Blue-black pigmentation in cartilage/tendons.

  • Asymptomatic until 3rd decade.

  • Urine: Darkens upon standing.

Maple Syrup Urine Disease (MSUD)

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • Absence of branched-chain -ketoacid dehydrogenase (BCKDH) complex (BCKDHA, BCKDHB, DBT genes)

• Hallmark Clinical Features & Odors

  • Odor: Maple syrup or burnt sugar (urine, breath, skin).

  • Lethargy, failure to thrive within a week.

Isovaleric Acidemia

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • Isovaleryl-CoA dehydrogenase (IVD)

• Hallmark Clinical Features & Odors

  • Odor: Sweaty feet (due to buildup of isovaleric acid).

Homocystinuria

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • CBS, MTHFR, MTR, MTRR, or MMADHC genes

• Hallmark Clinical Features & Odors

  • Lens dislocation (near-sightedness) due to lack of cysteine for collagen. Osteoporosis, mental retardation.

Citrullinemia Type 1

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • Argininosuccinate Synthase 1 (ASS1)

• Hallmark Clinical Features & Odors

  • Urea cycle disorder.

  • Lethargy, vomiting, seizures, coma due to toxic ammonia buildup.

Citrullinemia Type 2

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • SLC25A13 gene

• Hallmark Clinical Features & Odors

  • Urea cycle disorder.

  • Lethargy, vomiting, seizures, coma due to toxic ammonia buildup.

Argininosuccinic Aciduria

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • Argininosuccinate lyase (ASL)

• Hallmark Clinical Features & Odors

  • Urea cycle disorder.

  • Lethargy and unwillingness to eat within first few days of life.

Cystinuria

Aminoacidopathies: __________

• Defect (Enzyme/Gene)

  • SLC3A1 and SLC7A9 genes

• Hallmark Clinical Features & Odors

  • Inadequate renal reabsorption of cystine.

  • Formation of cystine stones in kidneys, ureters, or bladder.

Nephrotic Syndrome

• The Pattern: A massive drop in Albumin and a significant spike in the α2-macroglobulin peak.

• Why: In kidney disease, the "filter" is damaged. Small proteins like Albumin are lost in urine. The liver tries to compensate by overproducing larger proteins like α2-macroglobulin, which are too big to leak out.

Acute Phase Proteins (Acute Inflammation)

• The Pattern: A mild decrease in Albumin and a noticeable increase in α1 and α2 globulins.

• Why: The liver ramps up positive acute phase reactants (like Haptoglobin and α1-antitrypsin) during infection or trauma, causing these middle peaks to swell.

α1-Antitrypsin Deficiency

• The Pattern: A complete absence or near-total flattening of the α1 peak.

• Why: Since α1-antitrypsin makes up about 90% of the α1 globulin fraction, its genetic absence leaves a visible "void" in the graph. This is often linked to early-onset emphysema or liver cirrhosis.

Hypogammaglobulinemia

• The Pattern: A very flat or non-existent γ (Gamma) peak on the far right.

• Why: This indicates a deficiency in antibodies (Immunoglobulins). This can be congenital or acquired (e.g., due to certain leukemias or immunosuppressive drugs).

Monoclonal Gammopathy (M-Spike)

• The Pattern: A tall, narrow, "church-spire" peak in the Gamma region.

• Why: This is a classic sign of Multiple Myeloma. A single clone of plasma cells is pumping out a massive amount of one specific, identical antibody; spike in IgG.

Polyclonal Gammopathy

• The Pattern: A broad, "mountain-like" rise in the Gamma region.

• Why: Unlike the narrow spike in (E), this shows many different plasma cells are active. This is common in chronic infections, autoimmune diseases (like Lupus), or chronic liver disease.

Severe Hepatic Disease

• The Pattern: A significant decrease in Albumin and generally low peaks in the α and β regions.

• Why: The liver is the "protein factory." When it is severely damaged, it can no longer manufacture Albumin or the transport proteins found in the α and β zones.

Liver Cirrhosis

• The Pattern: A low Albumin peak and a unique "smearing" or "bridge" connecting the β and γ peaks.

• Why: This is the diagnostic hallmark of cirrhosis. It’s caused by increased IgA (which migrates between the Beta and Gamma zones), making it impossible to see where one peak ends and the next begins; beta-gamma bridge.

Hepatic Damage

Total Protein (TP): NORMAL or DECREASE

Albumin: DECREASE

Globulin: INCREASE

Key features: Cirrhosis & Hepatitis

Infections

Total Protein (TP): NORMAL or DECREASE

Albumin: DECREASE

Globulin: INCREASE

Key features: Acute & Chronic

Inadequate Diet / Nephrotic Syndrome

Total Protein (TP): DECREASE

Albumin: DECREASE

Globulin: NORMAL

Immunodeficiency

Total Protein (TP): DECREASE

Albumin: NORMAL

Globulin: DECREASE

Dehydration

Total Protein (TP): INCREASE

Albumin: INCREASE

Globulin: INCREASE

Multiple Myeloma

Total Protein (TP): INCREASE

Albumin: NORMAL

Globulin: INCREASE