Spectrum of LMX1B mutations: from nail-patella syndrome to isolated nephropathy.

Nail-patella syndrome (NPS) is an autosomal-dominant disease caused by LMX1B mutations and is characterized by dysplastic nails, absent or hypoplastic patellae, elbow dysplasia, and iliac horns. Renal involvement is the major determinant of the prognosis for NPS. Patients often present with varying degrees of proteinuria or hematuria, and can occasionally progress to chronic renal failure. Recent genetic analysis has found that some mutations in the homeodomain of LMX1B cause isolated nephropathy without nail, patellar or skeletal abnormality (LMX1B-associated nephropathy). The classic term "nail-patella syndrome" would not represent disease conditions in these cases. This review provides an overview of NPS, and highlights the molecular genetics of NPS nephropathy and LMX1B-associated nephropathy. Our current understanding of LMX1B function in the pathogenesis of NPS and LMX1B-associated nephropathy is also presented, and its downstream regulatory networks discussed. This recent progress provides insights that help to define potential targeted therapeutic strategies for LMX1B-associated diseases.

Nail-patella syndrome, infantile nephrotic syndrome: complete remission with antiproteinuric treatment.

A girl, second child of healthy parents, was referred to the Renal Unit at the age of 9 months with haematuria (230 RBC/microl) and proteinuria (2.4 g/l). Serum creatinine was normal (0.25 mg/dl), albumin low (34 g/l) and cholesterol elevated (223 mg/dl). Physical examination showed bilateral webbing of the elbows, equinovarus of both feet and absent patellae. The clinical diagnosis of nail-patella syndrome was confirmed by demonstrating a splice mutation in the intron 5 (750 + 1 G>A) of the LMX1B gene. Treatment with enalapril for 2 years (0.1-1 mg/kg per day) did not bring about any change in urinary protein excretion. However, enalapril (1 mg/kg per day) associated with losartan (1 mg/kg per day) resulted in complete remission (proteinuria 140 mg/24 h) at the age of 7 years.

[Kidney involvement in hereditary osteo-onychodysplasia]. / Porazhenie pochek pri nasledstvennoi osteoonikhodisplazii.

Review of the literature and case report concern renal damage in hereditary osteo-onychodysplasia (nail-patella syndrome). This syndrome is a rare genetic disease inherited by the autosome-dominant type. It arises because of underdevelopment of tissues of mesodermal and ectodermal origin and is characterized by hypoplasia or absence of patella, ulnar dysplasia, nail plate dystrophy, growths on the iliac bones, renal affection. The disease was detected in early childhood. Renal affection presented with urinary syndrome with a concurrent nephrotic syndrome later on followed by moderate arterial hypertension and progression to renal failure. Renal biopsy revealed the picture of focal segmentary glomerular hyalinosis typical for this disorder. Because immunodepressants were thought inadequate, the treatment included lovastatin and inhibitors of angiotensin-converting enzyme to inhibit non-immune mechanisms of the disease progression.

Insulin antagonistic effects of growth hormone in short children.

Growth hormone has several insulin antagonistic effects. To determine the time course of these effects in growth-hormone-treated children, the frequently samples intravenous glucose tolerance test was used to measure insulin sensitivity (SI) and glucose effectiveness (Sg) before, and 1 week, 1 month and 6 months after beginning growth hormone therapy in 3 patients with growth hormone deficiency (GHD), 3 patients with non-growth-hormone-deficient short stature (NGHD) and 3 with Turner syndrome (TS). Pretreatment SI was lower in TS than in the other two groups (p < 0.05), but Sg did not differ between groups. Mean SI levels 1 week and 1 month after starting growth hormone therapy were not different from before growth hormone [1.67 +/- 0.26 x 10(-4) (pmol/l)-1 min-1]. SI after 6 months of growth hormone [0.67 +/- 0.15 x 10(-4) (pmol/l)-1 min-1] was lower than before and 1 week after growth hormone (p < 0.005). SI responses did not differ between groups. Sg, glucose tolerance, blood pressure, triglyceride, and cholesterol levels did not change, but the incremental insulin response increased with growth hormone therapy. Thus, in this small study 6 months of growth hormone therapy decreased SI, but did not affect other cardiovascular risk factors.