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At a glance

It is an autosomal recessive disease characterized by defective transport of the dibasic amino acids. Clinically, it is characterized by failure to thrive, poor growth during childhood, hepatomegaly, splenomegaly, lung involvement, sparse hair, and muscle hypotonia. Patients affected present a normal development to moderate mental retardation.

Synonym

Hyperdibasic Aminoaciduria Type II.

Incidence

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 140 patients have been described in the literature.

Genetic inheritance

Transmission is autosomal recessive, with the defect linked to chromosome 14q11.2.

Diagnosis

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.

Clinical aspects

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 the 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.

Precautions before anesthesia

An anesthesiology consultation is highly recommended before elective surgical procedures. It is recommended to obtain a complete cell blood count, clotting screen, electrolytes, BUN, and creatinine, liver, and kidney function tests. In ...

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