<unk>  is the result of mutations on the PEPD gene, located on chromosome 19 and coding for the<unk>  Enzyme, also known as peptidase-D. At least 19 different mutations in the PEPD gene have been identified in individuals affected by the disorder.<unk> -catalysed cleavage of a dipeptide to yield proline and, in this case, alanine.<unk>  has an autosomal recessive pattern of inheritance.<unk>  is involved in the degradation of certain iminodipeptides (those containing C-terminal proline or hydroxyproline) formed during the breakdown of collagen, recycling the constituent amino acids (proline and hydroxyproline) and making them available for the cell to reuse – not least in the synthesis of new collagen. This recycling by<unk> , seen in the image above, is essential for maintaining proline-based systems in the cell, such as the collagen-rich extracellular matrix (ECM), which serves to physically support the structure of internal organs and connective tissues. Inadequate recycling due to a dysfunctional<unk>  enzyme, caused by an appropriate mutation in the pertinent gene, leads to the deterioration of that support structure and therefore the connective tissue of the skin, capillaries, and the lymphatic tissue, as is the case in<unk> . In particular, it has been proposed that the buildup of non-degraded dipeptides might induce programmed cell-death (apoptosis), whereafter the cell's contents would be expelled into the neighbouring tissue potentially resulting in inflammation and giving rise to the dermatological problems seen in<unk> . Similarly, a dysfunctional collagen metabolism will likely interfere with physiological remodelling processes of the extracellular matrix (which require collagen to be dynamically degraded and rebuilt), which might cause problems with the skin, as well. The mental impairment observed in those with<unk>  might reasonably arise from complications involving neuropeptides, proteins that have an abundance of proline and are involved with communication in the brain. The condition is inherited in an autosomal recessive fashion, meaning that both copies of the gene contained in every cell (both alleles) are mutated. Each of the parents of the person who suffers from an autosomal recessive disorder possesses one copy of the mutant gene, but they usually do not exhibit the signs and symptoms of the disorder, as their other copy is functional and can compensate for any deleterious effects.
Prolidase deficiency
Dopamine transporter deficiency syndrome
Beta-ketothiolase deficiency
Dopamine beta hydroxylase deficiency
Gerstmann syndrome
Aromatic L-amino acid decarboxylase deficiency
Contiguous gene syndrome
Eruptive hypomelanosis