In lysinuric protein intolerance (LPI), defective transport of cationic amino acids at the basolateral membrane of the polar epithelial cells in the intestine and renal tubules leads to decreased intestinal absorption and excessive renal loss of lysine, arginine, and ornithine. Citrulline supplementation partially restores the function of the urea cycle that is impaired by deficiency of arginine and ornithine, but does not correct the chronic lysine deficiency. Previous attempts to supplement lysine orally have been hindered by profuse diarrhea, probably caused by excess lysine remaining unabsorbed in the gut. However, individually adjusted minute doses of L-lysine hydrochloride at mealtimes are tolerated well, but the long-term benefits of this therapy remain unknown. The aim of the study was to investigate the long-term benefits and possible adverse effects of oral lysine supplementation in patients with LPI. Supplementation of meals with low doses of oral lysine improved fasting plasma lysine concentrations in 27 Finnish patients with LPI without causing hyperammonemia or other recognizable side effects during 12 months of follow-up. In conclusion, low-dose oral lysine supplementation is potentially beneficial to patients with LPI and can be started safely at an early age.

In lysinuric protein intolerance (LPI), intestinal absorption and renal tubular reabsorption of arginine, ornithine, and lysine are impaired due to a defective cationic amino acid transporter. Deficiency of arginine and ornithine restricts the function of the urea cycle, leading to hyperammonemia after protein load, and to strong protein aversion. Mealtime supplements of citrulline, another urea cycle intermediate that uses other transport mechanisms, prevent postprandial hyperammonemia and improve protein tolerance. Deficiency of lysine, an essential amino acid, most probably also contributes to the symptoms of LPI. We investigated possibilities to improve the availability of lysine for tissues by increasing plasma lysine concentration. Six patients with LPI were started on short-term oral lysine supplementation that was administered with their regular citrulline doses and standard low-protein meals. L-Lysine in consecutive doses of 0.55 and 1.1 mmol/kg caused profuse diarrhea in first 3 patients. To avoid gastrointestinal side effects, the 3 other patients were started on smaller lysine supplements of only 0.05 mmol/kg per dose, given 3 times daily for 3 days. All pre- and postprandial plasma lysine concentrations remained within normal range in 2 of the 3 patients studied. Even after the larger doses, no significant effects on the urea cycle were seen. We conclude that low-dose oral lysine supplementation normalizes plasma lysine concentration in patients with LPI, and is safe and well tolerated at least in short-term use.

This article is the third and last in a series entitled The Finnish Disease Heritage I-III. All the 36 rare hereditary diseases belonging to this entity are described for clinical and molecular genetic purposes, based on the Finnish experience gathered over a period of half a century. In addition, five other diseases are mentioned. They may be included in the list of the "Finnish diseases" after adequate complementary studies.

Although L-arginine is the only substrate for nitric oxide (NO) production, no studies have yet been reported on the effect of an L-arginine deficiency on vascular function in humans. Lysinuric protein intolerance (LPI) is a rare autosomal recessive defect of dibasic amino acid transport caused by mutations in the SLC7A7 gene, resulting in an L-arginine deficiency. Vascular endothelial function was examined in an LPI patient who was shown to be a compound heterozygote for two mutations in the gene (5.3-kbp Alu-mediated deletion, IVS3+1G-->A). The lumen diameter of the brachial artery was measured in this patient and in healthy controls at rest, during reactive hyperemia (endothelium-dependent vasodilation [EDV]), and after sublingual nitroglycerin administration (endothelium-independent vasodilation [EIV]) using ultrasonography. Both EDV and NO(x) concentrations were markedly reduced in the patient compared with those for the controls. They became normal after an L-arginine infusion. EIV was not significantly different between the patient and controls. Positron emission tomography of the heart and a treadmill test revealed ischemic changes in the patient, which were improved by the L-arginine infusion. Thus, in the LPI patient, L-arginine deficiency caused vascular endothelial dysfunction via a decrease in NO production.

The diagnosis and treatment of osteoporosis is an important aspect of gynecologic training and practice. Idiopathic juvenile osteoporosis (IJO) is a rare disease of children and adolescents that resolves after the onset of puberty. A case report is presented and current methods of diagnosis and treatment of IJO are discussed as well as the differential diagnosis. A MEDLINE search was performed of the following terms: idiopathic juvenile osteoporosis, pediatric osteoporosis, adolescent osteoporosis, bisphosphonates pediatric adolescent, and pregnancy osteoporosis, and references from bibliographies of selected papers were used as well. All papers in English, French, and German are considered in this review. There were 114 papers selected as relevant to the topic. Data relevant to the diagnosis, pathogenesis, methods of imaging, laboratory evaluation, differential diagnosis, and treatment of IJO are presented. IJO is a diagnosis of exclusion in the pediatric and adolescent patient with osteoporosis. Although bone density gradually improves after the onset of puberty, treatment of currently affected children and adolescents involves activity restriction, calcium, vitamin D, and bisphosphonate therapy. Future reproductive concerns are discussed and areas requiring additional study are reviewed.

Obstetricians & Gynecologists, Family Physicians

After completion of this article, the reader will be able to describe the condition idiopathic juvenile osteoporosis, compare the clinical features of this condition to other similar conditions, outline the diagnostic workup of a child with this condition, and list the potential therapeutic options for a patient with idiopathic juvenile osteoporosis.