Only two patients from one family have been described with P5C
synthase deficiency.4,6 These patients’ clinical
signs were indicative of involvement of both the nervous system and
the connective tissue. Particular manifestations included muscular
hypotonia, frequent vomiting, failure to thrive, cutis laxa, hyperextensible joints,
developmental delay, seizures in infancy, cataracts, progressive
spasticity, and severe intellectual deficit later in life. As P5C synthase
acts at the interface between ornithine and proline synthesis, both
hypoprolinemia and hypoornithemia are characteristic diagnostic
features. As a consequence of hypoprolinemia, citrulline and arginine
are low as well, and hyperammonemia may occur as a result of insufficient
supply of these substrates to the urea cycle. Treatment with ornithine
and proline has not been effective in preventing the clinical manifestations.
(For an overview of the clinical, biochemical, and diagnostic features
and treatment of disorders affecting ornithine metabolism, see eTable 142.2.)