APPENDIX I: BIOCHEMICAL BASIS OF DISEASES

Albinism (oculocutaneous albinism)

OMIM #203100, #203200, #203290, and #606574

At least four variations exist, all of which impact the production of the pigment melanin.

The varying types of albinism affect hair and skin pigments as well as vision to varying degrees.

There is no cure for albinism. Treatment is supportive, including any necessary visual/eye care as well as preventative care to prevent sunburn and skin cancers.

Variations that only affect the eyes (ocular albinism) are also known, which are all X-linked.

Type 1: Deficit in tyrosinase, the first enzyme in the melanin synthetic pathway. Variations of type 1 exist.

Type 1 albinism patients can have no, some, or even temperature-dependent (increased in cooler body parts) pigment formation. A variation affects predominately Amish/Mennonite peoples.

Type 2: Defect in the P-protein, which regulates melanocyte pH and affects pigment production. The melanocortin 1 receptor on melanocytes, which binds pituitary hormones called melanocortins (e.g., ACTH and MSH) also regulate the production and type of melanin produced in type 2 albinism.

Type 2 (the most common type) has some pigment production (e.g., moles, freckles, and light hair color) and less problems with vision.

Type 3: Defect in tyrosinase-related protein-1 (TRP-1), involved in melanin synthesis but also possibly affecting and regulating tyrosinase activity and melanocyte proliferation and death.

Type 3 is less understood but results in reddish hair, red-brown skin, and blue/gray eyes.

Type 4: Defect in membrane-associated transporter protein (MATP), regulating melanin synthesis and melanocyte differentiation.

Type 4 is usually found only in Japan, although a small German population has also been identified. Patients have white to yellow to even brown hair, light blue/gray to brown eyes, and visual problems.

Alkaptonuria (black urine disease)

OMIM #203500

Defect in the gene for homogentisic acid oxidase. Breakdown of phenylalanine and tyrosine is inhibited, leading to increase of the intermediate homogentisic acid (2,5-dihydroxyphenylacetic acid), also known as alkapton. Excessive alkapton is excreted in the urine and, when exposed to air, turns into a brown-black, ...