Chapter 5: Genetic and Congenital Disorders

1. Phenylketonuria [PKU]

Cause: deficiency in liver enzyme PAH that converts phenylalanine to tyrosine -> elevated phenylalanine levels toxic to brain - high in protein-rich foods and diet food [aspartame as artificial sweetener] - fasting and starvation increases muscle catabolism Manifestations: - intellecutal impairment and impaired neurologic developement

2. Neurofibromatosis

Cause: genetic defect in tumor suppressor genes that regulate cell differentiation and growth [Schwann cell tumors in NS] Type 1 Neurofibromatosis/von Recklinghausen Disease: - Cause: neurofibromas in peripheral nerves - Manifestation: cutaneous and subcutaneous neurofibromas (bubbles on skin) AND cafe au lait spots (large, flat pigmentations) Type 2 Neurofibromatosis/Bilateral Acute: - Cause: neurofibromas in acoustic nerve - Manifestation: headache, hearing loss, and tinnitus

1. Marfan Syndrome

Cause: genetic mutation in extracellular matrix protein [fibrillin, elastic fiber] abundant in connective tissue Manifestations: - Skeletal: long body and extremeities, tapering fingers, hyperextensible joints - Cardiovascular: mitral valve prolapse, aorta weakness - Vision: bilateral lens dislocation

2. Tay-Sachs Disease

Cause: lysosomal storage disease in which hydrolytic enzyme deficiency increase sphingolipids in nervous tissue and failure to break down GM2 gangliosides in cell membranes Manifestations: - destruction of neurons -> gradual deterioration of motor and mental functions [fatal at age 4-5]

Inherited Multifactorial Disorders

Characteristics: - tend to involve a single organ or tissue derived from same embryonic development field - increased risk of recurrence in future pregnancies for same or similar defect - first-degree relatives of affected person has increased risk of having child with disease Examples: - Congenital disorders arising from multifactorial disorders include cleft lip and palate, clubfoot, and congenital heart disease. - Chronic diseases include coronary artery disease, diabetes mellitus, hypertension, and cancer.

Single Gene Disorders

Definition: caused by a defective or mutant allele at a single gene locus Effect: formation of abnormal proteins or decreased production of gene products Examples: - autosomal dominant and recessive disorders - X-linked recessive disorders

X-Linked Dominant Disorders

Heritability: 1. Female Heterozygotes [affected, XmXn] - female and male offspring both have 50% of having disease 2. Female Homozygotes [affected, XmXm] - female and male offspring both have 100% of having disease 3. Affected Males [XmY] - transmit mutant chromosome to all daughters and no sons Example: Fragile X Syndrome - causes intellectual impairment and more severe in affected males

X-Linked Recessive Disorders

Heritability: 1. Female Heterozygotes [carriers, XmXn] - female offspring have 50% of being carrier - male offspring have 50% of having disease 2. Female Homozygotes [affected, XmXm] - female offspring have 100% of being carrier - male offspring have 100% of having disease 3. Affected Males [XmY] - transmit mutant chromosome to all daughters - transmit mutant chromosome to no sons [transmit Y not X chromosome]

Autusomal Recessive Disorders

Mutant genes transmitted from both parents [affected or unaffected] to offspring

Autosomal Dominant Disorders

Single mutant gene transmitted from an affected parent to an offspring or manifested as new mutation