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An Osteoblastic Dysplasia Arch Dis Child: first published as 10.1136/adc.30.151.265 on 1 June 1955. Downloaded from RICKETS WITH ALKALINE PHOSPHATASE DEFICIENCY: AN OSTEOBLASTIC DYSPLASIA BY BERNARD SCHLESINGER, JOSEPH LUDER, and MARTIN BODIAN From The Hospitalfor Sick Children, Great Ormond Street, London (RECEIVED FOR PUBLICATION NOVEMBER 10, 1954) Since the introduction of better diets with ample when cod liver oil was also introduced, but the symptoms vitamin supplements by more enlightened mothers, gradually increased until she vomited all her feeds, and the virtual disappearance of infantile rickets due became restless, then drowsy and so dehydrated that to lack of vitamin D, increased interest has been parenteral fluids were required (weight at 71 months was growth from only 10 lb.). At no time was there any sign of infection aroused in similar disorders of bone and the stools were normal. Temperature was 100- to other causes. In studying metabolic, biochemical 103- F. and renal factors, which can all play a part, our One of the most striking features was a widely open, knowledge has become clearer of physiological tense, bulging anterior fontanelle, but the cerebrospinal bone growth, the mechanism whereby calcium and fluid was not under pressure and quite normal. The phosphorus are maintained at a constant level in the skull circumference (16j in.) was not increased. A blood, the part played by enzymes in calcification subdural haematoma was suspected and it was at this and of how deviation of these from the normal stage that she was transferred under our care. may be a feature of skeletal disorder. After an x-ray examination of the skull it was realized copyright. a care that some gross bone disorder was present. Obvious Recently girl of 7 months came under our enlargement of the epiphyseal region of the wrists, knees with hypercalcaemia, renal insufficiency and wide- and ankles, and 'beading' of the costochrondral spread radiological evidence of 'rachitic' osteo- junctions suggested that the condition was some form porosis, together with periosteal changes and of severe rickets, which was supported by further radio- bizarre bone formation. The diagnosis was very graphs of the skeleton, although they were not entirely puzzling and no account of similar cases in this typical. Otherclinical findings were rather blue sclerotics, eyes and generalized mild pigmentation. country could be found. Investigation showed a promiinent http://adc.bmj.com/ serum alkaline phosphatase far below the level associated with an abnormal and improperly Radiological Report. Dr. L. G. Blair and Dr. G. N. calcified matrix. Eventually references were found in Weber, reported as follows: the American literature to a rare disorder of skeletal GENERAL. The skeleton was poorly developed for the age (71 months); there was marked demineralization at growth in which hypophosphatasia appeared to be a the metaphyses and the growing margns of all the bones, primary factor. Clinically our case seemed to fall producing an irregular, ill-defined margin and in many into this group, and bone biopsy finally produced regions a faintly speckled ghost image of the subepiphy- additional confirmatory evidence. seal region, which was presumably poorly calcified on September 29, 2021 by guest. Protected osteoid tissue. LoNG BoNEs. The mid-shafts were normal. The Case Reports metaphyses showed an irregular margin, distal to which Case L.* C.A., a girl and only child (no miscarriages), was a zone of poorly calcified osteoid. In the femur was first admitted at the age of 7j months to the Kent and these zones were sharply demarcated, but elsewhere this Canterbury Hospital under the care of Dr. Stanley distinction was less marked. No cupping was present. Rodgers, to whom we are indebted for the early history. The epiphyseal lines were irregularly widened. Epiphy- Following a normal delivery (birth weight 7 lb. 4 oz) the seal development was slightly retarded. (Bone age at the baby seemed to thrive for a few weeks, but then began to wrist was 3 months.) vomit intermittently and ceased to gain weight regularly. Epiphyseal calification was irregular, being less dense Breast feeding was changed to dried milk at 3 month, centrally in most cases, but the cortex was affected in the same way. Early irregular periosteal new bone forma- * This case was shown to a meeting of the Section of Paediatrics, Royal Society of Medicine, in January, 1954, and a brief description tion was seen along the shafts of several bones, parti- appeared in the Proc. roy. Soc. Med., 1954, 47, 541. cularly the tibiae and humeri (Fig. 1). 265 Arch Dis Child: first published as 10.1136/adc.30.151.265 on 1 June 1955. Downloaded from FiG. 2.-Radigaph ( r a dof the skull of Case 1 at the age of 8 months, showing widened sutuis, a bulging anterior fon- tanelle and defective ossification. I: FIG. 1.-Radiograph of the lower limbs of Cas I at the am of 7+ months, showing regular c ion of the meaphyses and epi- physes, zones of poorly calcfied osteoid at the lower ends of the femora and early periosteal new bone formation aleng the shafts. copyright. http://adc.bmj.com/ on September 29, 2021 by guest. Protected FjG. 4-Increasing but irregular calification in Case 1 at ust over I year of a, with striking periosteal new bone formation along the shafts. FIG. 3.-Radiograph of the lower limbs of Case I at 11 months, show- ing improved but stil disordered osification with cupping of the bone ends Arch Dis Child: first published as 10.1136/adc.30.151.265 on 1 June 1955. Downloaded from AN OSTEOBLASTIC DYSPLASIA 267 FiG. 5.-The skull of Case 1 at 20 months is now wel ca,ified but FiG. 7.-The curious a ane of Case I at 14 months with deform- there is premature closure of the suures, producing abnormal growth ity of the skull as a result of cranioatenosis. of the vault. copyright. http://adc.bmj.com/ on September 29, 2021 by guest. Protected g L ,-- Z~~~~~~~~~M ~ ~ ~ ~ ~ ~ __ - - - JUNE JULY AUG. SEPT. OCT. NOV. DEC. JAN. FEB MAY AUG. SEPT -FG3 6-D194 FIG. 6.-iagram of the invetitio over a peiod of 11 mouthIs 19 Arch Dis Child: first published as 10.1136/adc.30.151.265 on 1 June 1955. Downloaded from 268 ARCHIVES OF DISEASE IN CHILDHOOD Rins. The rib ends, which were demineralized and ill there was a moderate anaemia (700o Hb), from which the defined, were slightly expanded. infant eventually recovered. An initial leucocytosis SKuLL. There was defective ossification throughout, (17,600 W.B.C. per c.mm.) with a normal differential resulting in widening of the sutures at the base and vault, count was present, but before long this disappeared. and irregular growing margins of the flat bones. Urine Most specimens of urine contained some pus Scattered flecks of calification in the suture lines were cells and a trace of albumin; usually they were sterile, presumably attempts at ossification in the osteoid tissue. but at times a light growth of Bact. coli was obtained. There was slight bulging of the enlarged anterior fon- The reaction was on the whole acid; amino-aciduria and tanelle (Fig. 2). glycosuria were absent. Urea clearance at the age of PELvis, SCAPuLAE, SpINE. Similar changes with fluffy I year in two successive specimens was 40- 90o (standard bone margins and patchy mineralization were present clarance) and 56 - 2 (maximum clarance), which, throughout. together with the constantly raised blood urea and poor During the months of June, July and August, 1953, excretion of dye on pyelography, indicated renal impair- slowly increasing changes of patchy demineralization ment. There were no retinal changes at this period. appeared at the bone ends, with extension of the perio- The urine was again examined by Dr. Charles Dent steal thickening to most of the long bones. The 22 months later, and he reported as follows: epiphyses became less dense and one or two of the 'The standard chromatogram showed a rather weaker carpal centres had alnost completely disappeared. pattern than for the previous urine examined on By September mineralization was improving through- January 25, 1953, as if to suggest that there was an out (Fig. 3). Periosteal thickening in the long bones increase in renal damage since that date. As far as we and ribs had increased and ossification at the sutures had could see from this, however, the pattern was normal. improved. The skull had a curious shape with bulging In view of our findings with the urine from McCance's of the vertex and deficient growth of the frontal region, as case we have done a further chromatogram, over-loaded the coronal and squamosal sutures were beginning to five times, so as to show the weaker spots more easily. close. This now makes it quite clear that there is a definite In October there was further improvement (Fig. 4). abnormality in this urine, for the over-loaded chromato- There was now wel-marked cupping of the bone ends, gram showed a good spot corresponding to ethano- weUl seen in the knees and ribs. lamine phosphate, not very strong but nevertheless quite On May 24,1954, when the child was 20 months old, pathological. It is possible that this was present in the development was still retarded and there was consider- previous urine but was not detected as we only did a copyright. able general porosis. The subperiosteal new bone was normal chromatogram.' now consolidating. The metaphyses remained cupped A positive calcium and phosphorus balance was and markedly irregular. Epiphyseal development was demonstrated by Dr. Payne and Dr. Wilkinson (Table I), slightly retarded. (The bone age at the wrist was 15 months.) TABLE 1 The skull was well calcified; the anterior fontanelle and CALCIUM AND PHOSPHORUS BALANCE ccronal and squamosal sutures had prematurely closed, Period 3 days Calcium Phosphorus causing restricted growth of the vault anteriorly and a ( )= daily () = dlailymg.
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