Autosomal recessive disease characterized by defective
transport of the dibasic amino acids. Failure to thrive, poor growth during
childhood, hepatomegaly, splenomegaly, sparse hair, and muscle hypotonia.
Normal development to moderate mental retardation.
Hyperdibasic Aminoaciduria type II.
The highest known incidence is observed in Finland with 1:60,000 live
births. Other areas with a high incidence are Japan, Italy, and Turkey;
however, only approximately 100 patients have been described in the literature.
Transmission is autosomal recessive, with the
defect linked to chromosome 14q11.2.
Caused by a defect in the renal and intestinal transport
system for lysine and for ornithine and arginine (dibasic amino acid
transport). In contrast to patients with cystinuria, these patients do not
have increased urinary cystine excretion.
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.
An anesthesiology consultation is highly
recommended before elective surgical procedures.
Proper evaluation of intravascular volemia,
electrolyte imbalance, and feeding habits. The patient should be admitted
the day before surgery to allow proper fluid resuscitation and electrolyte correction. Obtain a
coagulation profile and bleeding time; if abnormal, correct immediately.
Anemia is often present and requires correction. In the presence of
moderate-to-severe hyperammonemia, elective surgery should be delayed until
proper correction, to avoid neurologic deficit.
No reports about anesthesia in these
patients were found. Obtain ...