Schimke immuno-osseous dysplasia (SIOD, MIM 242900) is an autosomal-recessive pleiotropic disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction and T-cell immunodeficiency. Using genome-wide linkage mapping and a positional candidate approach, we determined that mutations in SMARCAL1 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1), are responsible for SIOD. Through analysis of data from persons with SIOD in 26 unrelated families, we observed that affected individuals from 13 of 23 families with severe disease had two alleles with nonsense, frameshift or splicing mutations, whereas affected individuals from 3 of 3 families with milder disease had a missense mutation on each allele. These observations indicate that some missense mutations allow retention of partial SMARCAL1 function and thus cause milder disease.

Schimke immuno-osseous dysplasia (SIOD) is characterized by spondyloepiphyseal dysplasia, nephropathy, and T-cell deficiency. SIOD is caused by mutations in the putative chromatin remodeling protein SMARCAL1. We report an 8-year-old boy with SIOD and recurrent, severe, refractory migraine-like headaches. Through a retrospective questionnaire-based study, we found that refractory and severely disabling migraine-like headaches occur in nearly half of SIOD patients. We have also found that the vasodilator minoxidil provided symptomatic relief for one patient. We hypothesize that these headaches may arise from an intrinsic vascular, neuroimmune, or neurovascular defect resulting from loss of SMARCAL1 function.

We studied the influence of both a high-glucose-concentration dialysate (717 mg/dl) and intravenous mannitol (1g/kg) on the serum osmolality changes in stable patients on chronic dialysis. During regular dialysis, serum osmolality fell 10 mosmol/kg H2O. This fall was reduced to 5.2 mosmol/kg H2O when the high-glucose-concentration dialysate was used, and to 4.3 mosmol/kg H2O when intravenous mannitol was used. When the two methods were combined, the serum osmolality fall was reduced to 1.7 mosmol/kg H2O. The clinical signs of disequilibrium declined (from 67% to 10%) in parallel with the decline in serum osmolality changes. This fall was independent of the ultrafiltration rate. A high-glucose-concentration dialysate and intravenous mannitol can each reduce the osmolality changes that occur during hemodialysis, but when used alone, intravenous mannitol is more effective of the two. The reduction of osmolality changes also leads to reduction of the mild clinical signs usually associated with disequilibrium.

A 3-year, 8-month-old male was admitted into hospital for nephrologic assessment. He had had frequent episodes of diarrhea and vomiting since he was 4 months old. He had normal intellectual and neurological development. His weight was 9.5 kg (p<3; average for 10 months) and his stature was 71 cm (p<3; average for 8 months), with short trunk ( Fig. 1; body upper/lower segment measurements: 38.7/32.3 cm), short neck and triangular face with a bulbous nose. Growth velocity was 1.6 cm/year. The abdomen was prominent and there were multiple lentigines on the face and trunk. There were microdontia, a high-pitched voice, and a staggering gait. He had a non-affected older sister, and his parents were not consanguineous.The hemogram showed ferropenic anemia (hemoglobin 10.4 g/dl, normal 11.5-13.5; MCV 74.2 fl, normal 75-87; hematocrit 31.5%, normal 42-54; and serum iron 30 µg/dl, normal 59-158), lymphopenia (1.49×10 9 lymphocytes/l, normal 1.5×10 9 -6.5×10 9 ) and thrombocytosis (600×10 9 platelets/l, normal 184×10 9 -465×10 9 ). Clinical chemistry demonstrated elevated total cholesterol (769 mg/dl, normal 50-230) and hypertryglyceridemia (1022 mg/dl, normal 50-200), and reduced albumin (1.6 g/dl, normal 3.5-5.3) and total protein in serum (4.7 g/dl, normal 6-8), while glucose, electrolytes and creatinine (0.4 mg/dl, normal 0.4-0.8) were normal. The 24-h urine specimen demonstrated features of nephrotic syndrome with severe proteinuria (118.9 mg/m 2 /h = 2.85 g/24 h, which evolved to 9.9 g/24 h 3 months later). The cross-linked N-terminal telopeptides of type I collagen (NTx) were high in the 2-h fasting morning urine sample (499 nM ECO/mM creatinine, normal 3-63), indicating an abnormally high bone turnover. There were no mucopolysaccharides in the urine. The albumin/β 2 -microglobulin index confirmed glomerular proteinuria. Immunologic analysis demonstrated an inverse CD4/CD8