722 Amyoplasia: A Distinguishable Form of Arthrogryposis

Abstract

A girl presented on the 9th day of life with familial lactic acidosis, euglycemia and hepatomegaly; death occurred at day 15. Ratios for plasma lactate: pyruvate (130:l) and B-hydroxybutyrate: acetoacetate (38:l) were elevated suggesting an imbalance of tissue NAD:NADH. Plasma pyruvate (0.?.5mM, Norm = <.07mM) and alanine (1.7mM, Norm = C.4rnl-l) were both elevated indicating a defect in pyruvate utilization. Organic acids other than those above were not elevated in urine. Skin fibroblasts produced excess lactic acid in culture. Evolution of 14-co2 (nmoleslmg prot hr f S.D.) from 1mM L-114~ lactate (control = 19.8 f 9.4), L-114~ pyruvate (control = 41.1 f 4.7) or L -~1 4~ alanine (control = 12.7 f 4.1) was markedly decreased compared to control cells (< lo%, C 1% and <lo% respectively).Thiamine (0.7mM) or lipoic acid (0.OlmM) for 1 or 24 hours of preincubation had no effect. Dichloroacetate (50pM) produced a modest increase of lactate utilization (150% increase) in the patient's cells, but the effect of methylene blue on alanine utilization (0.27mM) was dramatic (1100% increase), bringing it within the normal range (7.8-20.5nmoles CO2lmg prot hr).Our findings suggest that methylene blue can repair lactic acidosis in vitro and may be of use in patients whose cellular regeneration of NAD is impaired. Bilirubin glucuronyl transferase activity (BGT) is negligible in jaundiced (jj) Gunn rats, with intermediate and higher levels in heterozygous (Jj) and outbred (JJ) rats, respectively. This could be explained either by a defective enzyme or structural defects in the endoplasmic reticulum in which the enzyme is compartmented. If the latter interpretation is correct, similarly segregating activities might be expected among other microsomal enzymes. The activity of aminopyrine demethylase (AD), a hepatic microsomal mixed-function oxidase, was assayed in male jj, Jj, JJ Gunn and Wistar (Wi) rats. BGT (pg bilirubin conjugated130 minlmg protein N) and AD (moles CH 0 producedlminlmg protein) are shown below (mean+SD) . Results: j5 AD < Jj, JJ or Qi AD (p < .05). Ftest demonstrated AD variance in Jj > jj or JJ rats (p < .05). A correlation (rc.81) exists between BGT an& AD (p < .01) in JJ rats, but not in Jj rats. The data suggests a microsomal membrane defect in enzyme compartmentation may be the primary abnormality in the Gunn rat and possibly in Crigler-Najjar Syndrome. Of particular interest was the denonstration of mrd-finding difficulties and problem in the use of syntax as major factors in the expressive language deficit. Except for difficulties with syntax, receptive language skills were relatively normal. These results suggest that left-henisphere-based difficulty i n serial order processing may be associated with the XXY anmly, as ccmpared with right-hanisphere deficits in spatial processing that have been associated with XO Turner syndrane. Propionate is formed by the catabolism of isoleucine, valine, threonine and methionine, by the oxidation of odd-numbered carbon chain fatty acids and by the degradation of the t...