| Abstract|| |
Osteomalacia is a common occurrence world over due to the deficiency in vitamin D and calcium intake. We present here two sisters with features of sever osteomalacia, myopathy and hypophosphatemia hyperparathryroidism and 25(OH)D2, 25(OH)D3and 1,25(OH)D3 levels were very low.
|How to cite this article:|
Jabur WL. Familial vitamin D deficient osteomalacia and renal osteodystrophy: Shaping up the debate. Saudi J Kidney Dis Transpl 2010;21:128-30
|How to cite this URL:|
Jabur WL. Familial vitamin D deficient osteomalacia and renal osteodystrophy: Shaping up the debate. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2013 May 19];21:128-30. Available from: http://www.sjkdt.org/text.asp?2010/21/1/128/58787
| Introduction|| |
It is rarely reported nowadays the severe skeletal manifestations of osteomalacia secondary to vitamin D deficiency, especially among young females, of Arabic descent who are working outdoor and residing in the Persian gulf region where a hot sunny climate prevails around the year. The main risk factors are usually dark skin and intake of vegetarian diet. Similarly the renal osteodystrophy related to vitamin D deficiency is often encountered and has still debatable etiology. By reporting these patients we are trying to discover the probable etiology and the pathological mechanisms underlying osteomalacia and renal osteodystrophy.
| Case History|| |
Two sisters 29and 28 years old from Arabic descent were referred from the neurology clinic for further management. Their main complaint was lower limb proximal muscle wea kness that had progressed in severity over the last two years. A primary diagnosis of proximal myopathy was made. Both had dark skin with remarkable history of bilateral lower limb proximal muscular weakness. Electromyographic and nerve conduction studies revealed myopathic changes. Radiological examination of the pelvis and lower limb showed generalized osteopenia, multiple collapsed fractures of the vertebrae, and loosers zone in the proximal femure. Other investigations showed borderline serum calcium and phosphorus, remarkably elevated bone alkaline phosphatase, 24hour urinary excretion of calcium and phosphorus were very low, parathyroid hormone was dramatically elevated, and 25(OH)D2, 25 (OH)D3 and 1,25(OH)D3 levels were very low. Antigliadin antibodies were negative. Renal and hepatic functions were normal. They also had iron deficiency anemia. A primary diagnosis of osteomalacia was made and treatment with vitamin D in the form of 25(OH)D2 and calcium was commenced.
| Discussion|| |
Its obvious that the osteomalacia is secondary to vitamin D deficiency which is reflected by very low serum 25(OH)D2 < 10 nmol/L (normal range 75-200) and low 1, 25(OH)D3 23 pmol/L (normal range 43-140). The increased parathyroid hormone tries to maintain serum calcium within normal limits by sacrificing the bone matrix, however to a marginal degree in our patients (serum calcium is 8.3and low urinary calcium and phosphorus excretion). This highlights the pivotal role of vitamin D in calcium and phosphorus homeostasis.
We are reporting this case for several reasons. Being familial is an unusual feature for osteomalacia secondary to vitamin D deficiency. The drastically low 25(OH)D (severe vitamin D deficiency defined as serum 25(OH)D below 20 nmol/L) and the severity of the disease are unexpectedly out of proportion to the currently reported tempo of the disease in general. The mutual presentation of osteomalacia in both of the sisters as a myopathic syndrome is unusual. Whether the patients are having unique inherent predisposition to develop myopathy or it's a presentation of vitamin D deficiency, needs further clarification. Pure vegetarian diet was the only risk factor; nevertheless such diet causing an advanced osteomalacia is difficult to explain solely.
Proximal myopathy has been reported in osteomalacia  , however the debate remains that is it the hypovitaminosis D, hypocalcemia, hypophosphatemia, or the secondary hyperparathyroidism is the culprit. It is understandable that deficiency of 1,25(OH)2D in renal failure patients is parallel to the decline in renal function, nevertheless the presence of deficiency of the 25(OH)D which is usually severe and also widely recognized in such patients is more than expected.  One probable theoretical reason that needs further exploration is the acquired enzymatic defect in the pathway of 25 (OH) vitamin D synthesis . On the other hand, living in the gulf region would abrogate the supposition of under exposure to the ultra violet light which is commonly encountered in the northern latitude.  The first contrasting feature to nonuremic osteomalacia is the prominent hypocalcimea despite the presence of a recognizable secondary hyperparathyroidism early in the disease process. This might be explained either by poor responsiveness of bone to higher level of parathyroid hormone or by the fact that the fraction of ionized calcium is raised by the acidic milieu causing negative feed back the parathyroid gland.  Proximal myopathy is not a common presentation in uremic patients nevertheless, there are several confounding factors to cause the muscle disease in chronic renal failure.  The second significant outstanding variance from non-uremic osteomalacia is the hyperphosphatemia which incurred despite the prominent deficiency of 1, 25(OH) 2D3 and the secondary hyperparathyroidism that are encountered at earlier stages in the chronic renal failure. Hyperphosphatemia is directly related to the decline in GFR  contrary to our patients where etiology of hypophosphatemia was not related to increased urinary excretion due to secondary hyperparathyroidism causing hyperphosphaturia.  Thereupon three intriguing inquiries we have to emphasize on, first; is there any genetically determined defect that could address the sever deficiency in the synthesis of 25(OH)D in osteomalacia in general and uremia in particular? The second, is there any confounding factors that could worsen the disease in nonuremic osteomalacia,like hypophosphatemia?, third, for our patients, is there any genetically or aquired defect that could address the proximal myopathy as the presenting feature in nonuremic osteomalacia? Considering the clinical presentation of proximal myopathy in both sisters, suggests a genetically determined deficiency in synthesis of 25(OH)D in osteomalacia. Similarly the suspicion of Fanconi syndrome can not be entertained by the absence of glucosuria and aminoaciduria. Hypophosphatemia might be the culprit to cause the proximal myopathy, since it's a widely recognized feature in phosphate deficient osteomalacia.  The unremarkable history of gastrointestinal and hepatobiliary diseases and the negative Anti-gliadin antibody speak against it being as a cause. Osteomalacia is a very common disease all over the world and it may be on the rise in the gulf region also.
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Wael Latif Jabur
New Medical Center Specialty Hospital, P.O. Box 7832, Dubai
United Arab Emirates