Phenotype presentation of hypophosphatemic rickets in adults.

Hypophosphatemic rickets (HR) is a group of rare disorders caused by excessive renal phosphate wasting. The purpose of this cross-sectional study of 38 HR patients was to characterize the phenotype of adult HR patients. Moreover, skeletal and endodontic severity scores were defined to assess possible gender differences in disease severity in patients with genetically verified X-linked HR. Compared to normal reference data, i.e., z = 0, HR patients had significantly lower final height, with a mean difference in z-score of -1.9 (95% CI -2.4 to -1.4, P < 0.001). Compared to paired z-scores of final height, z-scores of leg length were significantly lower and those of sitting height were significantly higher (P < 0.001), resulting in disproportion as indicated by the significantly elevated sitting height ratio, mean difference in z-score of 2.6 (95% CI 2.1-3.1, P < 0.001). Z-scores of head circumference (median 1.4, range -0.4 to 5.5, P < 0.001) and z-scores of bone mineral density (BMD) of the lumbar spine (median 1.9, range -1.5 to 8.6, P < 0.001) were significantly elevated compared to normal reference data. The relative risk (RR) of fracture was reduced (RR = 0.34, 95% CI 0.20-0.57, P < 0.001). The skeletal severity score tended to be higher in males compared to females (P = 0.07), and no gender difference in endodontic severity was found. In conclusion, adult HR patients were characterized by short stature and were disproportioned. They had elevated BMD of the lumbar spine and a reduced risk of fractures. We found a tendency for males to be more severely affected than females.

Nutritional rickets in Denmark: a retrospective review of children's medical records from 1985 to 2005.

INTRODUCTION: This study describes clinical and biochemical characteristics of nutritional rickets and risk factors at diagnosis among children living in Denmark. All medical records from patients with rickets referred to or discharged from hospitals in Southern Denmark from 1985 to 2005 were identified by register search. MATERIALS AND METHODS: Patients included were younger than 15 years of age and fulfilled the diagnostic criteria of primary, nutritional rickets. A total of 112 patients with nutritional rickets were included: 29 were of ethnic Danish origin, and 83 were immigrants. RESULTS: Patients diagnosed before the age of 4 (median 1.4) years displayed the classic clinical signs of rickets, whereas patients diagnosed after the age of 4 (median 12.5) years had few clinical signs and unspecific symptoms. Ethnic Danish patients were only diagnosed before age 24 months, and they accounted for 73% of all cases presenting with hypocalcemic seizures, but biochemically, they did not have more severe rickets. Of patients diagnosed before the age of 4 years, 45% were ethnic Danish. In early childhood, insufficient or no vitamin D supplementation was given in 88% of all cases. Among immigrant girls older than 4 years of age, 78% were veiled. DISCUSSION: Nutritional rickets in Denmark is predominantly a disease among immigrants, but ethnic Danish patients comprised nearly half of all patients diagnosed before the age of 4 years, and they presented more frequently with hypocalcemic seizures. The main risk factors were omitted, such as vitamin D prophylaxis among the youngest patients and veiling among older children/teenagers.

Incidence and prevalence of nutritional and hereditary rickets in southern Denmark.

OBJECTIVE: To estimate the incidence of nutritional rickets and the incidence and prevalence of hereditary rickets. DESIGN: Population-based retrospective cohort study based on a review of medical records. METHODS: Patients aged 0-14.9 years referred to or discharged from hospitals in southern Denmark from 1985 to 2005 with a diagnosis of rickets were identified by register search, and their medical records were retrieved. Patients fulfilling the diagnostic criteria of primary rickets were included. RESULTS: We identified 112 patients with nutritional rickets of whom 74% were immigrants. From 1995 to 2005, the average incidence of nutritional rickets in children aged 0-14.9 and 0-2.9 years was 2.9 and 5.8 per 100,000 per year respectively. Among immigrant children born in Denmark, the average incidence was 60 (0-14.9 years) per 100,000 per year. Ethnic Danish children were only diagnosed in early childhood and the average incidence in the age group 0-2.9 years declined from 5.0 to 2.0 per 100,000 per year during 1985-1994 to 1995-2005. Sixteen cases of hereditary rickets were diagnosed during the study period giving an average incidence of 4.3 per 100,000 (0-0.9 years) per year. The prevalence of hypophosphatemic rickets and vitamin D-dependent rickets type 1 was 4.8 and 0.4 per 100,000 (0-14.9 years) respectively. CONCLUSIONS: Nutritional rickets is rare in southern Denmark and largely restricted to immigrants, but the incidence among ethnic Danish children was unexpectedly high. Hereditary rickets is the most common cause of rickets in ethnic Danish children, but nutritional rickets is most frequent among all young children.

Activating glucokinase (GCK) mutations as a cause of medically responsive congenital hyperinsulinism: prevalence in children and characterisation of a novel GCK mutation.

OBJECTIVE: Activating glucokinase (GCK) mutations are a rarely reported cause of congenital hyperinsulinism (CHI), but the prevalence of GCK mutations is not known. METHODS: From a pooled cohort of 201 non-syndromic children with CHI from three European referral centres (Denmark, n=141; Norway, n=26; UK, n=34), 108 children had no K(ATP)-channel (ABCC8/KCNJ11) gene abnormalities and were screened for GCK mutations. Novel GCK mutations were kinetically characterised. RESULTS: In five patients, four heterozygous GCK mutations (S64Y, T65I, W99R and A456V) were identified, out of which S64Y was novel. Two of the mutations arose de novo, three were dominantly inherited. All the five patients were medically responsive. In the combined Danish and Norwegian cohort, the prevalence of GCK-CHI was estimated to be 1.2% (2/167, 95% confidence interval (CI) 0-2.8%) of all the CHI patients. In the three centre combined cohort of 72 medically responsive children without K(ATP)-channel mutations, the prevalence estimate was 6.9% (5/72, 95% CI 1.1-12.8%). All activating GCK mutations mapped to the allosteric activator site. The novel S64Y mutation resulted in an increased affinity for the substrate glucose (S(0.5) 1.49+/-0.08 and 7.39+/-0.05 mmol/l in mutant and wild-type proteins respectively), extrapolating to a relative activity index of approximately 22 compared with the wild type. CONCLUSION: In the largest study performed to date on GCK in children with CHI, GCK mutations were found only in medically responsive children who were negative for ABCC8 and KCNJ11 mutations. The estimated prevalence (approximately 7%) suggests that screening for activating GCK mutations is warranted in those patients.

[Prevalence of coeliac disease (CD) in children with type 1 diabetes (T1D)]. / Høj praevalens i Region Syd af cøliaki blandt børn med type 1-diabetes. Sygdomsopsporing samt opfølgning på glutenfri diaet--sekundaerpublikation.

This screening study was performed to determine the prevalence of coeliac disease (CD) in children with type 1 diabetes (T1D) and to estimate the clinical effects of a gluten-free diet. In the region of Southern Denmark all patients under 16 years of age with T1D were identified and 269 (89%) were included. CD was diagnosed in 33 (12.3%). Patients with CD had a lower height SDS and weight SDS and were younger at diabetes onset. After 2 years on a gluten-free diet there were significant improvements in clinical and biochemical parameters. We recommend screening of CD in all children with T1D.

Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years' follow-up.

OBJECTIVE: This study was performed to 1) determine the prevalence of celiac disease in Danish children with type 1 diabetes and 2) estimate the clinical effects of a gluten-free diet (GFD) in patients with diabetes and celiac disease. RESEARCH DESIGN AND METHODS: In a region comprising 24% of the Danish population, all patients <16 years old with type 1 diabetes were identified and 269 (89%) were included in the study. The diagnosis of celiac disease was suspected in patients with endomysium and tissue transglutaminase antibodies in serum and confirmed by intestinal biopsy. Patients with celiac disease were followed for 2 years while consuming a GFD. RESULTS: In 28 of 33 patients with celiac antibodies, an intestinal biopsy showed villous atrophy. In 5 patients, celiac disease had been diagnosed previously, giving an overall prevalence of 12.3% (95% CI 8.6-16.9). Patients with celiac disease had a lower SD score (SDS) for height (P < 0.001) and weight (P = 0.002) than patients without celiac disease and were significantly younger at diabetes onset (P = 0.041). A GFD was obtained in 31 of 33 patients. After 2 years of follow-up, there was an increase in weight SDS (P = 0.006) and in children <14 years old an increase in height SDS (P = 0.036). An increase in hemoglobin (P = 0.002) and serum ferritin (P = 0.020) was found, whereas HbA(1c) remained unchanged (P = 0.311) during follow-up. CONCLUSIONS: This population-based study showed the highest reported prevalence of celiac disease in type 1 diabetes in Europe. Patients with celiac disease showed clinical improvements with a GFD. We recommend screening for celiac disease in all children with type 1 diabetes.

[Vitamin D1alpha-hydroxylase deficiency as the cause of severe rickets in a 1-year-old-old boy]. / D-vitamin-1 alpha-hydroxylase-mangel som årsag til svaer rakitis hos en etårig dreng.

We describe a 15-month-old boy referred to the hospital because of delayed development of motor skills and growth retardation. Blood samples and X-rays of the wrists and knees revealed rickets. He was treated with oral calcium and vitamin D with modest clinical and biochemical effect. 1,25-dihydroxyvitamin D was undetectable in laboratory tests. Vitamin D1alpha-hydroxylase deficiency was suspected and confirmed by DNA analysis, which revealed a 7 bp duplication in exon 8 of the CYP27B1 gene. The treatment was changed to an activated formula of vitamin D, alphacalcidol, whereupon the clinical and biochemical symptoms rapidly improved.