540 a Keratan and Heparan Sulfaturia - A New Mucopolysac- Charidosis With N-Acetylglucosamine 6− Sulfatase Deficiency

Abstract

Advances in the development of banding techniques have facilitated the identification of a number of new chromosomal abnormalities. We studied a 13 mo. old girl with a history of failure to thrive, developmental delay and dysmorphic features. Chromosomal analysis revealed ringed chromosome 12. J.T. was the product of an uncomplicated second pregnancy of a 24 yr. old woman. Birth weight and height were close to the 3rd percentile. At 13 mos. her weight age was 1 mo., height age was 3 mos. and head circumference was at 3rd percentile for 3 mos.She had epicanthal folds, mildly cupped low set ears, high arched palate, short neck with low set hairline. Total hand length was that of a 1.5 mo. old and clinodactyly and single crease of left 5th finger. Developmentally she functioned between 5-8 mos. The chromosome number was 46 in all cells and trypsin banding showed a ring 12 chromosome. Tvelve percent o f cells showed variable chromosome loss and 4 showed gaps or breaks in chromatids. The purpose of this report is to delineate the clinical findings and natural history of ring chromosome 12 syndrome. There are only two known cases of this syndrome with which we compared our findings. It appears that the amount of genetic material deleted from chromosome 12 determines the degree of physical abnormalities and developmental delay. The relatively high rate of the loss of the ring 12 points out the fragility of the ring chromosome. A patient with Turner Syndrome (TS) (45,XO) diagnosed by age 2 years had at age 5 years, rachitic changes on chest x-ray, a healing traumatic fracture of the left femur and metaphyseal changes consistent with hypophosphatasia (H). The diagnosis was confined by a low serum alkaline phosphatase (AP) (125 mu/ml) in the presence of a fracture, elevated urinary excretion of phosphoethanolamine (PEA) (33.6 mglday) and early shedding of deciduous teeth. Malabsorption, glomerular and tubular renal diseases were excluded by appropriate investigations. Because of limited growth potential in TS and further impairment by the concomnitent occurence of H, a trial of phosphate therapy was felt to be indicated. A bone biopsy after tetracycline labelling was performed prior to the initiation of therapy; biopsy will be repeated after 6 months of therapy (1/78). The clinical response to therapy suggests a nearly twofold increase in growth rate. IHistorically and radiologically the paternal side was free of disease; 4/7 in the mother's sibship showed radiographic evidence of bone dysplasia in childhood. Total AP was low in the mother and her affected sister, and normal in the father. PEA excretion studies and AP isoenzyme determinations are inprogres This is the first report of the simultaneous occurrence of T5 and H. The family study suggests that the H is transmitted as an autosomal dominant trait. CoA can be carboxylated to form EMA, and hexanoyl CoA can be either U-oxidized to AA or conjugated with glycine to form HG, this pattern of urinary metabolites suggested a deficiency of butyryl CoA dehydrogenase, a mito...