We report on 44 patients (18 with additional affected family members), with congenital distal limb contractures identified from a large study of over 350 patients with congenital joint contractures. Fourteen propositi (seven familial cases, seven isolated cases) had a newly recognized form of arthrogryposis, which we have designated distal arthrogryposis type 1, with the predominant manifestations of autosomal dominant inheritance; tightly clenched fists at birth, with medially overlapping fingers, ulnar deviation, and camptodactyly in adults; and positional foot deformities. Contractures at other major joints are variable. There are no associated visceral anomalies; intelligence is normal. There can be marked intrafamilial and interfamilial variability. Twenty-two propositi with similar distal contractures had additional findings and were classified into five subcategories of distal arthrogryposis (type IIA-E). Among type II patients cleft palate, cleft lip, small tongue, trismus, ptosis, epicanthal folds, keratoconus, short stature, scoliosis, a unique hand position, and dull normal intelligence were seen. These characteristics were seen in various combinations and patterns and allowed sorting into groups that were the basis for the categorization. The remaining eight propositi were recognized to have previously described conditions with distal contractures and autosomal dominant inheritance, ie, the Freeman-Sheldon syndrome, trismus-pseudo-camptodactyly syndrome, congenital contractural arachnodactyly, and familial camptodactyly. Pathogenetically we postulate similar underlying defects of abnormal tendon attachments, attenuation, and absence; careful nosologic comparisons are important for prognostic counseling and habilitative management.

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 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...