Ординатура / Офтальмология / Английские материалы / Handbook of Nutrition and Ophthalmology_Semba_2007

mutation but not in mice with the proline-347 → serine (P347S) mutation (280). These results suggested that vitamin A was beneficial for class II rhodopsin mutants, as in the T17M mutation, but not for class I rhodopsin mutants, as in the P347S mutation (280). Oral vitamin A supplementation at the level of 15,000 IU/d appears to be safe for the treatment of retinitis pigmentosa in healthy adult men and nonpregnant women who eat a regular diet without excessive intake of food high in vitamin A (281). Annual monitoring of liver enzymes and triglycerides is recommended for patients on supplementation (281). A recent randomized controlled clinical trial shows that docosahexaenoic acid, in addition to vitamin A supplementation, does not slow the course of disease of patients with retinitis pigmentosa (282). A subgroup analysis suggested that for patients who were commencing vitamin A therapy, the addition of docosahexaenoic acid slowed the course of the disease for 2 yr (283).

13. MAPLE SYRUP URINE DISEASE

Maple syrup urine disease is a rare autosomal recessive disorder characterized by deficiency of branched-chain α-keto acid dehydrogenase with resulting accumulation of branched-chain amino acids leucine, isoleucine, and valine and branched-chain α-keto acids. In 1954, John Menkes and colleagues described four infants with progressive cerebral degeneration and urine that had an odor resembling maple syrup (284). Subsequent investigations showed high concentrations of leucine, isoleucine, and valine (285) and 2,4-dinitrophenylhudrazones in the urine (286). Six loci contribute to the branchedchain α-keto acid dehydrogenase complex. There are five phenotypes of the disease: classic, intermediate, intermittent, thiamine-responsive, and dihydrolipoyl dehydrogenase (E3)-deficient (287). The worldwide frequency of maple syrup urine disease is approximately 1 in 185,000 births, but in the inbred Old Order Mennonite population of Lancaster and Lebanon Counties in Pennsylvania, the frequency has been reported as 1 in 176 newborns (288).

The classic phenotype of maple syrup urine disease is the most common form and includes neonatal onset of poor feeding, weight loss, alternating hypertonia and hypotonia, ketoacidosis, and maple syrup odor to the urine. Ophthalmic findings include optic atrophy, ophthalmoplegia, strabismus, nystagmus, and cortical blindness (289,290). Loss of corneal epithelium has been described in one infant with isoleucine deficiency (291). Treatment of maple syrup urine disease consists of limiting the dietary intake of leucine, isoleucine, and valine. A trial of thiamin therapy is recommended to determine whether the infant may have a thiamin-responsive form of the disease (287). Commercial synthetic formulas are available for maple syrup urine disease, and long-term dietary management can reduce the morbidity and mortality associated with the disease.

14. MOLYBDENUM COFACTOR DEFICIENCY AND ISOLATED SULFITE OXIDASE DEFICIENCY

Molybdenum cofactor deficiency and sulfite oxidase deficiency are two related inborn errors of metabolism that are associated with severe neurological abnormalities, ectopia lentis, and mental retardation. Molybdenum cofactor deficiency is characterized by deficient activity of three enzymes: sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase, whereas isolated sulfite oxidase deficiency is associated with deficient sulfite

oxidase activity, but normal molybdenum cofactor, xanthine dehydrogenase, and aldehyde oxidase activity. Combined sulfite oxidase deficiency and xanthine oxidase deficiency has also been described (292). Both molybdenum cofactor deficiency and sulfite oxidase deficiency are characterized by seizures, psychomotor retardation, facial dysmorphia, hypertonia and hypotonia, dilated ventricles, and brain atrophy. Spherophakia and ectopia lentis are associated with both molybdenum cofactor deficiency and isolated sulfite oxidase deficiency (293–296). Elevated S-sulfocyteine concentrations may be used for the diagnosis of sulfite oxidase deficiency. Molybdenum cofactor deficiency is not reversible with dietary measures, but there have been reports of some success with limiting the dietary intake of sulfur amino acids in sulfite oxidase deficiency (297).

15. OTHER

Familial hyperlysinemia is an autosomal recessive disease in which there is a defect in lysine degradation due to defective α-aminoadipic semialdehyde synthase (298). The clinical manifestations include subluxation of the lens (299). Dietary restriction of proteins may help to reduce plasma lysine concentrations but does not appear to influence long-term development, which may be normal despite high levels of lysine (300).

16. CONCLUSIONS AND RECOMMENDATIONS

Some inborn errors of metabolism show that nutritional modification or intervention can reduce the risk of visual loss and blindness or slow progression of disease. In other conditions, nutritional interventions have had limited effects. The research agenda for these diverse groups of metabolic diseases includes understanding the pathogenic mechanisms involved in Refsum disease, measuring the long-term effects of a phytanic acidrestricted diet on the progression of ocular disease, determining whether a galactose-free, rather than galactose-restricted, diet in the first 6 mo of life will have better long-term outcome. Effective therapies are needed for the treatment of Menkes syndrome.

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