King George III I don't blame you...

King George III of the United Kingdom is well known for his bouts of hysteria and porphyria.
What's porphyria?

Porphyrias are inborn errors of metabolism. They are characterized by the increase or elevation of Amino Levulinic Acid or Porphyrins. (Look down for a brief pathway of Heme synthesis).
There are many types of porphyrias but I will explain just what King George III had.

He had what is called Acute Intermittent Porphyria.
It is an inherited condition with the enzyme Uroporphyrinogen - 1 - synthase (Porphobilinogen deaminase) deficient.
Since PBG deaminase catalyses the conversion of Porphobilinogen to Hydroxymethylbilane, there's an increase in porphobilinogen and a secondary increase of ALA synthase's (Amino Levulinic Acid) activity and hence ALA and PBG increases in quantity.
Now, when ALA and PBG both increase they tend to be elevated in the urine too but they're colourless so it doesn't show in the urine UNTIL it is left to be oxidized and it turns into a coloured urine.

ALA and PBG elevation can cause neuropsychiatric symptoms whilst increase in porphyrins can cause cutaneous photosensitivity.

In AIP, ALA and PBG is elevated and it explains the bouts of madness presented by King George III. Although the rest of the symptoms are quite different in their manifestations.

Did you know: Hurler's Syndrome and Pseudo-Hurler's syndrome (1st April 2009)

Hurler's Syndrome:
It is an autosomal recessive catabolism disorder of the proteoglycans. Hydrolases that break the glycosaminoglycans present in the proteoglycans structures, inside the lysosomes are deficient. Due to this, products like dermatan sulphate and heparan sulphate accumulates in the lysosomes instead of being excreted in the urine.
Mental Retardation and mesenchymal defects are seen in the patient.

Pseudo-Hurler's syndrome:
It is due to the reduced availability of GlcNAc phosphtransferase that converts mannose to mannose-6-phosphate that is targeted to the lysosomes. Instead due to the fact that they are not converted they are sent out of the cell.
Psychomotor retardation and skeletal deformities are prominent.