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Prenatal bowing of the long bones is often associated with severe bone dysplasias. We report a child who presented marked bowing of the long bones at birth but showed a relatively benign postnatal course with spontaneous improvement of bowing. The fetal imaging showed normal skeletal mineralization and normal chest and abdominal circumferences despite the limb bowing and shortening. Decreased serum alkaline phosphatase activity and elevated urine phosphoethanolamine was biochemically evident, and compound heterozygous mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene were identified, which confirmed the diagnosis of a benign form of prenatal hypophosphatasia. Benign prenatal hypophosphatasia should be considered in the differential diagnosis of congenital bowing of the long bones.

We have carried out a mutation screening of the PHEX gene in Finnish patients with hypophosphatemia. A total of 100% (5/5) of the familial HYP patients (X‐linked hypophosphatemia) and 93% (14/15) of the sporadic cases were found to carry a mutation in the PHEX gene. We identified 18 mutations, of which 15 were novel. We report also a new polymorphism 46bp upstream of exon 16. Two families were segregating the same nonsense mutation in exon 1 (R20X), but since this mutation has been previously reported in three independent studies, we consider it to be a mutational hotspot rather than a Finnish founder mutation. We did not find PHEX gene mutations in two additional hypophosphatemia families in which the mode of inheritance was other than X‐linked dominant. Also, no mutation could be detected in a patient with suspected oncogenic osteomalacia (OHO). Hum Mutat 15:383–384, 2000. © 2000 Wiley‐Liss, Inc.

X-linked hypophosphataemic rickets (XLH) results in defective bone mineralization and impaired growth. Treatment with oral phosphate (Pi) and calcitriol improves but does not normalize growth. This study assessed whether pubertal growth and metabolic control contribute to the height deficit. Study included patients with XLH who were treated with Pi-calcitriol from diagnosis to adult height; their hospital records, biochemistry and radiographs were reviewed. Six females with XLH were included. Their mean peak height velocity and total height gain during puberty were nearly normal despite deteriorating metabolic control. In treated girls with XLH, the pubertal growth is nearly normal despite suboptimal metabolic control. The major height loss occurs prior to puberty and is not recovered during the pubertal growth spurt.

To evaluate the bone mineral status of children being treated for X-linked hypophosphatemia, including potential differences between cortical bone in the radial diaphysis and combined cortical and trabecular bone in the lumbar spine. Forty-four bone mineral evaluations were performed in 11 children and adolescents with X-linked hypophosphatemia. Bone mineral density (BMD) of the lumbar spine and the radial diaphysis were measured by dual X-ray absorptiometry (DXA), second metacarpal cortical thickness was measured on hand radiographs, and these results were expressed as Z-scores (standard deviations from the mean). For the 11 initial examinations, Z-scores (mean+/-SD) were: radial BMD, -2.73+/-1.15, lumbar BMD, +1.28+/-1.53; and cortical thickness, -2.21+/-0.95. Lumbar BMD Z-scores were significantly greater than those for radial BMD and cortical thickness. On follow-up examinations there was a mild increase in radial BMD and decrease in lumbar BMD. Although these changes were statistically significant, they were quite small and the discordance between radial and lumbar BMD was not corrected. Children and adolescents who are being treated for X-linked hypophosphatemia manifest a bone mineral disorder characterized by decreased BMD in the appendicular skeleton and increased BMD in the lumbar spine. Although current therapy is successful in its anti-rachitic effects, it does not correct this bone mineral disorder and additional therapeutic trials should be considered.

Although the simplest way to correct bone deformity is one-stage correction, the problem associated with that method is overstretching of the soft tissues, which limits the correction and leads to complications such as compartment syndrome or peripheral nerve palsy. If an adequate amount of tissue necessary for correction is formed in advance, the deformity can be corrected safely at one stage without overstretching of the tissues. A leg lengthening technique was employed to form the necessary tissues. After leg lengthening with an unilateral external fixator (Hifixator), deformities were corrected manually at one stage without anesthesia, and the corrected positions were again secured with the fixator. To correct rotational deformity, two sets of pins were inserted into the proximal bone fragment of the tibia at the time of the operation, and after lengthening the proximal pin clamp of the fixator was disconnected from one pin set and reconnected to the other set. We applied this method to four tibias of three patients without any complications. The tension of the tissues was monitored using a pressure sensor built into a Hifixator to prevent the tissues from overstretching. During and after the correction, the tension of the tissue was maintained at less than before the correction.

X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children as well as hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a detrimental effect on patient outcomes. In this Evidence-Based Guideline, we recommend that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Whenever possible, the diagnosis should be confirmed by molecular genetic analysis or measurement of levels of fibroblast growth factor 23 (FGF23) before treatment. Owing to the multisystemic nature of the disease, patients should be seen regularly by multidisciplinary teams organized by a metabolic bone disease expert. In this article, we summarize the current evidence and provide recommendations on features of the disease, including new treatment modalities, to improve knowledge and provide guidance for diagnosis and multidisciplinary care.In this Evidence-Based Guideline on X-linked hypophosphataemia, the authors identify the criteria for diagnosis of this disease, provide guidance for medical and surgical treatment and explain the challenges of follow-up.