Symptoms can become apparent any time after
birth, although breast-feeding seems to delay the onset (probably because of
its low-protein content). However, as soon as these patients receive
nutrition with a higher protein content, hyperammonemia, diarrhea, nausea,
vomiting, and even coma may occur. If undiagnosed, additional clinical
symptoms, including failure to thrive as a consequence of the episodes of
diarrhea and vomiting, mild-to-moderate hepatosplenomegaly, osteoporosis,
and sparse scalp hair, may develop. Hyperammonemia is usually present only
after protein feeding, which is thought to be the result of a disturbance in
the urea cycle secondary to decreased levels of arginine and ornithine.
Mild-to-severe anemia has been reported in some of these patients who are on
a low-protein diet with citrulline replacement. Osteoporosis is often severe
and in childhood results in fractures after only minor trauma.
Glomerulosclerosis and chronic interstitial lung disease are not uncommon. A
potential fatal complication in these patients is an interstitial pneumonia
with alveolar proteinosis. The cause for complication is unknown.
Intermittent hemophagocytotic lymphohistiocytosis with increased levels of
ferritin and lactate dehydrogenase and an association with systemic lupus
erythematosus have been reported to be a regular feature of this
syndrome. l-Arginine deficiency was also responsible for vascular
endothelial dysfunction via a decrease in nitric oxide production, which
became normal after an l-arginine infusion. In another report, the
l-arginine deficiency was found to be responsible for thrombocytopenia
and increased antithrombin III levels, which normalized after an l-arginine infusion or transdermal nitroglycerin application. Mental
development is usually normal, although frequent and long-lasting episodes
of hyperammonemia are considered deleterious for the brain, and amazing
recoveries have been reported under strict diet.