Rheumatology 2001; 40: 107-108
© 2001 British Society for Rheumatology
Letters to the Editor |
Identical twins with hypercalcaemia due to Lowe's syndrome
Division of Endocrinology and
1 Department of Surgery, Philipps University, Marburg, Germany
SIR, We describe the unusual diagnosis of Lowe's syndrome (oculocerebrorenal syndrome) in identical twins at age 46 yr, who were referred to our institution for evaluation of hypercalcaemia and bone pain.
Two 46-yr-old identical twin brothers presented with a 1-yr history of hypercalcaemia. Both had grown up in a foster care family and had required chronic haemodialysis for end-stage kidney disease of unknown aetiology for 9 and 10 yr, respectively. On physical examination, short stature, kyphoscoliosis, bilateral tibial bone pain, bilateral cataracts and facial dysmorphic features (deep-set eyes, microcephaly, prominent forehead and baldness) were noted. Neuropsychological evaluation revealed an IQ of 70 in each patient, stubborness and tantrums. Examination of the neck, chest and abdomen was unremarkable. Laboratory assessment revealed end-stage kidney disease, hypercalcaemia [2.7 and 2.6 mmol/l (normal range 2.0–2.5) respectively], parathyroid hormone levels of 1110 and 1077 pg/ml (normal range 10–55) and increased biochemical markers of bone formation [osteocalcin 115 and 200 ng/ml (normal range 4–12)], and bone resorption [deoxypyridinoline 80.3 and 71.4 nmol/l (normal level 
11)]. Blood pH analysis revealed moderate compensated metabolic acidosis (pH 7.34, base excess 4 mmol/l), whereas a morning urine specimen revealed failure to acidify (pH 7.0). Ultrasonography of the neck and scintigraphic imaging using technetium-99m-MIBI demonstrated enlargement of all four parathyroid glands. Bone densitometry revealed severe osteoporosis with Z-scores of -3.0 and -2.6, respectively. Because of local pain in the left knee in one twin brother, an X-ray was performed and revealed moderately severe subperiosteal resorption in the lateral femur condyle (Fig. 1
).
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A diagnosis of tertiary hyperparathyroidism was made, and because of the bone pain, osteoporosis, high bone turnover and excessively high parathyroid hormone levels, surgery was scheduled. Intraoperative neck exploration confirmed the presence of enlarged parathyroid glands, and total parathyroidectomy with autotransplantation of parathyroid tissue into the forearm contralateral to the haemodialysis shunt was performed. Post-operatively, the patients transiently required calcium (3 g/day) and 1
,25-dihydroxycholecalciferol (1500 IU/day). Parathyroid hormone levels returned to normal and on follow-up 2 months after surgery serum concentrations of calcium, parathyroid hormone and biochemical markers of bone metabolism were normal without specific therapy. Because of the similar disease pattern with facial dysmorphic features and involvement of multiple organs in genetically identical subjects, a hereditary disorder was considered and a diagnosis of Lowe's syndrome (oculocerebrorenal syndrome) was made.
Lowe's syndrome is a rare X-linked genetic disorder characterized by major abnormalities of the lens, brain and kidneys [1]. In its typical presentation, it leads to the clinical triad of cataract formation during early infancy, mental retardation and a broad range of renal abnormalities, including incomplete bicarbonate resorption, tubular acidosis and end-stage kidney disease [1, 2]. Skeletal abnormalities of Lowe's syndrome may include osteoarthritis, kyphosis, scoliosis and multiple arthropathies [2]. Lowe's syndrome is caused by an inherited deficiency of the enzyme inositol-bisphhate 5-phosphatase due to nonsense or stop codon mutations of the OCRL gene, resulting in inappropriately low levels of phosphatidyl inositol-4,5-bisphosphate, which is a critical metabolite involved in Golgi vesicular transport [3, 4]. The clinical manifestation with ocular, cerebral and renal involvement is due to high requirements of phosphatidyl inositol-4,5-bisphosphate by the affected organs. Renal tubular acidosis has been implicated in osteoporosis and attributed to the compensatory release of alkali and calcium from bone in order to neutralize protons [5]. Chronic renal bicarbonate wasting in patients with abnormalities in inositol phosphate metabolism, as in Lowe's syndrome, may be a rare, but important, cause of hyperparathyroidism.
Notes
Correspondence to: L. C. Hofbauer, Division of Gastroenterology and Endocrinology, Zentrum für Innere Medizin, Philipps University, Baldingerstrasse, D-35033 Marburg, Germany. 
References
- Lowe C, Terrey M, MacLachan E. Organic aciduria, decreased renal ammonia production, hydrophthalmus and mental retardation: a clinical entity. Am J Child Dis1952;83:164–84.
- Charnas L, Gahl WA. The oculocerebrorenal syndrome of Lowe. Adv Pediatr1990;38:75–107.
- Attree O, Olivos IM, Okabe I et al. The Lowe's oculocerebrorenal syndrome gene encodes a protein highly homologous to inositol polyphosphate-5-phosphatase. Nature1992;358:239–42.[Medline]
- Suchy SF, Olivos-Glander IM, Nussbaum RL. Lowe syndrome, a deficiency of a phosphatidyl-inositol 4,5-bisphosphate 5-phosphatase in the Golgi apparatus. Hum Mol Genet1995;4:2245–50.
[Abstract/Free Full Text] - Weger M, Deutschmann H, Weger W, Kotanko P, Skabral F. Incomplete renal tubular acidosis in ‘primary’ osteoporosis. Osteoporosis Int1999;10:325–9.[Web of Science][Medline]
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