Clinical utility of methionine restriction in adenosine kinase deficiency.

Adenosine kinase (ADK) deficiency is a rare autosomal recessive inborn error of metabolism involving the methionine and purine metabolic pathways. Prior reports show that most patients present in infancy with jaundice, hypotonia, developmental delay, and mild dysmorphic features. Characteristic biochemical findings included hypoglycemic hyperinsulinism, cholestasis, elevated liver functions, methionine, S-adenosylhomocysteine, and S-adenosylmethionine, with normal or mildly elevated homocysteine level. Brain imaging demonstrated atrophy, hydrocephalus, and delayed myelination. There are 26 reported patients of ADK deficiency, of which 14 patients were placed on a methionine-restricted diet. Clinical improvement with methionine restriction was not well described. CASE REPORT: We report an infant who presented at birth with persistently elevated ammonia (100-163 µmol/L), hypoglycemia, cholestasis, and liver dysfunction. The initial metabolic and genetic work-up was nondiagnostic, with only a mildly increased plasma methionine level (51 [<38 µmol/L]). Iron depositions in the liver and in lip mucosa led to suspicion of gestational alloimmune liver disease. Immunoglobulin therapy and exchange transfusion treatments demonstrated transient clinical and biochemical improvements. However, subsequent episodes of acute liver failure with development of neurological abnormalities led to further evaluation. Metabolic studies showed a 25-fold increase in plasma methionine level at 8 months of life (1022 [<38 µmol/L]) with white matter abnormalities on brain MRI. Expanded molecular testing identified the disease. Urinary purines profile showed elevations of adenosine and related metabolites. Introduction of a low-methionine diet resulted in rapid clinical amelioration, improvement of brain MRI findings, and normalization of liver functions and methionine levels.

Sapling leaf trait responses to light, tree height and soil nutrients for three conifer species of contrasting shade tolerance.

We developed models to describe the responses of four commonly examined leaf traits (mass per area, weight, area and nitrogen (N) concentration) to gradients of light, soil nutrients and tree height in three conifer species of contrasting shade tolerance. Our observational dataset from the sub-boreal spruce forests of British Columbia included subalpine fir (Abies lasioscarpa [Hook.] Nutt; high shade tolerance), interior spruce (Picea glauca × Picea engelmannii [Moench] Voss; intermediate shade tolerance) and lodgepole pine (Pinus contorta Dougl. ex Loud. var. latifolia; low shade tolerance) saplings from 0.18 to 4.87 m tall, in 8-98% of total incident light, from field sites with <17.6 kg ha(-1) to >46.8 kg ha(-1) total dissolved N. Leaf weights and areas showed strong positive responses to light and height, but little or no response to soil nutrients. Parameter estimates indicated that the shape of leaf weight and area responses to light corresponded with shade tolerance ranking for the three species; pine had the most linear response whereas spruce and fir had asymptotic responses. Leaf N concentration responded positively to soil nutrients, negatively to light and idiosyncratically to height. The negative effect of light was only apparent on sites of high soil nutrient availability, and parameter estimates for the shape of the negative response also corresponded to shade tolerance ranking (apine = -0.79, aspruce = -0.15, afir = -0.07). Of the traits we measured, leaf mass per area showed the least response to light, soil nutrient and height gradients. Although it is a common practice in comparisons across many species, characterizing these conifers by mean values of their leaf traits would miss important intraspecific variation across environmental and size gradients. In these forests, parameter estimates representing the intraspecific variability of leaf trait responses can be used to understand relative shade tolerances.