Low vitamin D status in children with sickle cell disease

OBJECTIVES: To examine vitamin D status in children with sickle cell disease (SCD)-SS and its relation to season and dietary intake. STUDY DESIGN: Growth, dietary intake, 25-hydroxyvitamin D (25-OHD), and parathyroid hormone levels were measured. Children with low and normal vitamin D status were compared. Low vitamin D status was defined as a serum concentration of 25-OHD <27.5 nmol/L. Serum 25-OHD and parathyroid hormone levels were compared among children with SCD-SS and healthy children. RESULTS: Children with SCD-SS (n=65), 5 to 18 years of age, were evaluated. Mean (+/-SD) serum 25-OHD concentration was 25.5 +/- 12.8 nmol/L; 65% of subjects had low vitamin D status. Low vitamin D prevalence was highest during spring (100%). Children with SCD-SS were at higher risk for low vitamin D status than healthy children. Vitamin D intake was lower in subjects with SCD-SS and low vitamin D than those with normal serum vitamin D status (P <.05). CONCLUSIONS: Low serum vitamin D status was highly prevalent in black children with SCD-SS. Vitamin D status was associated with season and dietary intake.     

Vitamin B6 status of children with sickle cell disease

PURPOSE: In vitro, vitamin B(6) has antisickling properties, but the effect of vitamin B status on the health of children with sickle cell disease-SS (SCD-SS) is not well described. The purpose of this study was to assess vitamin B(6) status of children with SCD-SS ages 3 to 20 years and determine its relationship to growth, dietary intake, and disease severity.PATIENTS AND METHODS: Vitamin B(6) status was assessed by serum pyridoxal 5-phosphate (PLP) concentration in subjects with SCD-SS and by urinary 4-pyridoxic acid (4-PA) concentration in other subjects with SCD-SS and healthy control children. Concentration of PLP was compared with anthropometric measures of growth and nutritional status, dietary intake, hematologic indices, and frequency of SCD-related illness. RESULTS: The PLP concentration of subjects with SCD-SS was 15.6 +/- 15.2 nmol/L. Seventy-seven percent had a PLP concentration below the deficiency criterion (20 nmol/L) suggested by the Dietary Reference Intakes (1998). Controlling for alkaline phosphatase, age, and gender, PLP concentration was associated positively with weight, body mass index, and arm circumference -scores and negatively with reticulocyte count. Urinary 4-PA was lower in children with SCD-SS versus controls, although 4-PA/creatinine values did not differ between groups. CONCLUSIONS: Children with SCD-SS had apparently low serum PLP concentrations in the absence of excess vitamin B(6) excretion, suggesting low vitamin B(6) status. Low serum PLP concentration was associated with indicators of poor nutritional status and may be related to increased hemolysis in children with SCD-SS.     

Plasma homocysteine levels and folate status in children with sickle cell anemia.

PURPOSE: A sensitive inverse relationship between plasma homocysteine concentration and folate status has been demonstrated. Although children with sickle cell anemia (SCA) are at potential risk for folate deficiency, plasma homocysteine levels have not been reported in such patients. Therefore, a study was designed to assess plasma homocysteine levels as a marker of folate status. DESIGN: Plasma homocysteine concentrations were measured in 120 children with SCA (102 in steady state and 18 during an acute complication) who had never received supplemental folic acid. Folate status was directly assessed in 34 of these patients. RESULTS: Plasma homocysteine levels in the patients with SCA and control subjects were similar. The mean value +/- 1 SD was 5.8+/-2.5 micromol/L (range, 1.6 to 14.1 micromol/L) in the patients with SCA and 6.1+/-2.7 micromol/L (range, 1.7 to 15.3 micromol/L) in 73 pediatric control subjects. In a subpopulation of the study group (34 children), simultaneous serum folate, red cell folate, and total homocysteine concentrations were also measured. Their serum folate and red cell folate concentrations were normal: 12.4+/-10.0 nmol/L (range, 1 to 42 nmol/L) and 604+/-374.7 nmol/L (range, 205 to 1741 nmol/L), respectively. There was no correlation of plasma homocysteine concentration with various clinical or laboratory measures or with red cell folate concentration. CONCLUSION: Folate stores in children with SCA not receiving folic acid supplements are adequate despite an underlying hemolytic anemia.     

Zinc status in children and young adults with sickle cell disease

Previous studies have suggested an association of zinc deficiency and short stature in some children and adults with sickle cell disease (SCD). As a result, zinc supplementation has been recommended for these patients. The mechanism for zinc deficiency in certain patients with SCD is unknown, although renal loss of zinc has been suggested as a contributing factor. The zinc status of 29 subjects with SCD and 18 black controls was studied. No evidence of zinc deficiency in our population with SCD was found when plasma and cellular zinc levels were measured. Likewise, levels of two zinc-dependent enzymes, alkaline phosphatase and delta-aminolevulinic acid dehydratase, were normal in these subjects with SCD. Although adolescent subjects with SCD tended to be shorter than control subjects, there was no correlation between the height-forage z score and plasma zinc levels (r = -.31). It was concluded that zinc deficiency was not present in our population with SCD, and that there was no correlation between plasma zinc levels and the height-for-age z score in growing adolescent patients with SCD. These findings suggested that zinc supplementation may not be necessary in all patients with SCD.     

Growth and nutritional status of children with homozygous sickle cell disease

BACKGROUND: Poor growth and under-nutrition are common in children with sickle cell disease (SCD). This review summarises evidence of nutritional status in children with SCD in relation to anthropometric status, disease severity, body composition, energy metabolism, micronutrient deficiency and endocrine dysfunction. METHODS: A literature search was conducted on the Medline/PUBMED, SCOPUS, SciELO and LILACS databases to July 2007 using the keywords sickle cell combined with nutrition, anthropometry, growth, height and weight, body mass index, and specific named micronutrients. RESULTS: Forty-six studies (26 cross-sectional and 20 longitudinal) were included in the final anthropometric analysis. Fourteen of the longitudinal studies were conducted in North America, the Caribbean or Europe, representing 78.8% (2086/2645) of patients. Most studies were observational with wide variations in sample size and selection of reference growth data, which limited comparability. There was a paucity of studies from Africa and the Arabian Peninsula, highlighting a large knowledge gap for low-resource settings. There was a consistent pattern of growth failure among affected children from all geographic areas, with good evidence linking growth failure to endocrine dysfunction, metabolic derangement and specific nutrient deficiencies. CONCLUSIONS: The monitoring of growth and nutritional status in children with SCD is an essential requirement for comprehensive care, facilitating early diagnosis of growth failure and nutritional intervention. Randomised controlled trials are necessary to assess the potential benefits of nutritional interventions in relation to growth, nutritional status and the pathophysiology of the disease.     

Homocysteinemia, serum folate and vitamin B12 in very young patients with diabetes mellitus type 1

BACKGROUND: Recently a link between hyperhomocysteinemia [HH(e)] and diabetic micro- and macrovascular complications has been reported. However, it is far from clear whether HH(e) is an epiphenomenon or a cause of angiopathic complications. OBJECTIVE: To try to clarify this question we studied adolescents and young diabetic patients without or with only initial complications. SUBJECTS: Plasma levels of basal homocysteinemia [H(e)], folate and vitamin B12 were measured in 76 young diabetic patients (age range 13.6-32.2 yr) and 70 normal volunteers matched for sex and age. In 68 diabetic patients and 53 controls we evaluated the levels of homocysteinemia 2 h after a methionine-loading test. METHODS: Total (free + protein bound) plasma H(e) level was measured by HPLC. RESULTS: Basal or post-load HH(e) occurred in 4.1% of diabetic patients and 12.4% of controls (frequencies not statistically different). In diabetic patients plasma homocysteine values were statistically lower than in controls, but this difference was present only in females. The females showed lower homocysteine values and higher folate levels than males only in the diabetic group. We did not find significant differences in H(e) levels between patients with early complications, late complications or without complications of any type. CONCLUSIONS: Considering very young diabetic patients, the risk of hyperhomocysteinemia does not appear to be greater than in normal controls. Furthermore, our data seem to demonstrate that HH(e) is not a preexisting condition in diabetic patients, even in those predisposed to early complications.     

Cholelithiasis in children with sickle cell disease

Abdominal ultrasonography was performed on 305 children with sickle cell disease (SCD) (285 SS and 20 S-beta-thalassemia) to establish the prevalence of cholelithiasis in Saudi children with SCD. Their ages ranged from 1 to 18 years (mean 10.45 years). Gallstones were demonstrated in 60 children, giving a prevalence of 19.7%. An additional 50 patients (16.4%) had only biliary sludge. The youngest patient with gallstones was 3 years old. There was a correlation between the presence of gallstones and increasing age. Patients with gallstones were also found to have higher serum bilirubin levels, but their hemoglobin, hematocrit, reticulocyte count, hemoglobin S, and hemoglobin F levels were not significantly different from those of patients without gallstones.     

Early blood transfusions protect against microalbuminuria in children with sickle cell disease

BACKGROUND: Microalbuminuria (MA) is an early indicator for glomerulopathy in sickle cell disease (SCD). PROCEDURE: We reviewed the medical records of asymptomatic patients ages 4-20 with sickle hemoglobinopathies, who were screened for MA in order to find out its prevalence and risk factors. RESULTS: Nineteen of 120 (15.8%) screened patients had MA detected by spot urine (mean albumin absolute value 6.95 +/- 0.56 mg/dl) and abnormal albumin to creatinine ratios (79.8 +/- 0.62 mg/g creatinine). Twenty four-hour urine collections confirmed 57% of MA cases by spot urine. There was no difference in hyperfiltration between positive and negative patients. From the MA-positive patients, 15 had SS (16.8% of SS group) and 4 had SC (18% of SC group). Nineteen percent of children 10 years of age or older had MA, as compared to 8% of the younger children (P = 0.018), demonstrating that increasing age is a risk factor for MA. There was a positive correlation between MA and acute chest syndrome. Young age at start of chronic transfusions was inversely related to MA and therefore renoprotective (P = 0.03). We did not see a protective effect in the group of patients taking hydroxyurea for a relatively short time, mean age at start of treatment 12 +/- 5 years; however the sample was small. CONCLUSIONS: We conclude that: (1) children with sickle cell hemoglobinopathies 10 years or older should be screened for MA and (2) chronic transfusions starting at an early age may be renoprotective.     

Gastric function and absorption of vitamin B12 in children with celiac disease

Gastric acid secretion in nineteen children with celiac disease remained almost unchanged and the level of fasting serum gastrin was comparable with that of a control group of the same age. The absorption of vitamin B₁₂ was significantly decreased, most clearly in the infants with celiac disease as compared with their controls. The serum B₁₂ level, however, was decreased only in the oldest children. The results suggest that the mucosal lesion in the small intestine is most extensive in the youngest children, but the absorption defect of vitamin B₁₂ becomes clinically significant only after a long duration of the disease and not in childhood.     

Status of vitamin D in children with sickle cell disease living in Madrid, Spain

Patients with sickle cell disease have vitamin D deficiency and poor bone health which makes them prone to have an increased risk of fractures and osteoporosis in adulthood. We performed a prospective, cross-sectional study in children diagnosed with sickle cell disease living in Madrid, Spain. The purpose of this study was to evaluate the status of vitamin D of these children. Patients 0?C16?years old were enrolled between 2008 and 2011. We studied demographics, calcium metabolism, and bone health, especially by measuring levels of 25-hydroxyvitamin D (25(OH)D), during different seasons of the year, and bone densitometry (beyond 4?years of age). Seventy-eight children were included in the study. Mean age was 4.8?±?4.3?years, and mean serum 25(OH)D level was 21.50?±?13.14?ng/ml, with no differences in 25(OH)D levels within different seasons. Fifty-six percent of children had levels of 25(OH) vitamin D of <20?ng/ml, whereas 79 and 18?% of them had levels of <30 and <11?ng/ml, respectively. Secondary hyperparathyroidism was observed in 25?% of children. Densitometry was performed in 33 children, and an abnormal z-score was seen in 15.2?% of them with no correlation with levels of 25(OH)D. Conclusions: Vitamin D deficiency is highly prevalent in children with sickle cell disease, who are residing in Madrid, Spain, and it is detected at a young age. We propose that early intervention may increase the possibility of an adequate bone density later in life.     

Correlation of serum ferritin with other tests of iron status in sickle cell disease

The iron status of 42 patients with homozygous SS disease, none of whom was on chronic transfusion therapy, was investigated using tests for serum ferritin, serum iron, serum transferrin, transferrin saturation, and free erythrocyte protoporphyrin. Correlation coefficients were computed between ferritins and the other test results. The mean ferritin level of the group as a whole showed significant inverse linear correlation with the mean transferrin and free erythrocyte protoporphyrin values. The mean ferritin of the subgroup with normal ferritin levels correlated significantly only with the mean free erythrocyte protoporphyrin value. The mean ferritin of the subgroup with high ferritin levels correlated significantly only with the mean transferrin value. In these patients who had received only sporadic blood transfusions, there was poor correlation of ferritin levels with age and number of transfusions.     

Diminished antibody response to hepatitis B immunization in children with sickle cell disease

Hepatitis B surface antibody titers were routinely measured in 150 children with sickle cell disease (SCD) after immunization, and the seroconversion rate was found to be lower than that in the general population (89% vs. 97%, P = 0.002). Most of the children who did not seroconvert after the series of 3 immunizations responded to booster injections (93%). Therefore, we recommend the measurement of hepatitis B surface antibody titers after immunization in those children with SCD at greatest risk for hepatitis B infection. An additional dose of hepatitis B vaccine should be administered to those without evidence of seroconversion.     

Hypocholesterolemia in Nigerian children with sickle cell disease

Reports of circulating lipids of children with sickle cell disease (SCD) in Nigeria disagree on the question of whether these children are at increased risk of cardiovascular disease (CVD). We therefore analyzed the serum of 40 females and 37 males with SCD, age 5-19 years, and equal numbers of age-matched controls for total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and homocysteine. Using bioelectrical impedance analysis, we documented a significant reduction in the per cent fat-free mass in the SCD males and increases in the per cent body fat in both the male and female children with SCD. Marked hypocholesterolemia was present in both genders (means, 100-102 mg/dl) and the LDL-cholesterol levels of the male and female subjects with SCD (54 mg/dl) were below the lower limit of the reference range (59-137 mg/dl). Serum triglycerides in the SCD subjects were in the middle of the reference range for children. Although the mean HDL-cholesterol levels of the SCD males (23.1 mg/dl) and females (24.5 mg/dl) were well below the lower limit of the reference range (35-84 mg/dl), respectively, the LDL-cholesterol/HDL-cholesterol ratios of the SCD subjects were not abnormal. The mean serum homocysteine concentrations of the male and female SCD subjects (9.4-9.6 micromol/l) were at the high end of the normal range. Collectively, these results indicate that children with SCD in northern Nigeria are not at increased risk of CVD. However, their marked hypocholesterolemia should be a cause of concern about the overall mortality and general well-being.     

Osteoarticular infections in children with sickle cell disease

Thirteen children with sickle cell disease were identified as having 14 episodes of osteoarticular infection in a review of 27 years' experience. There were eight episodes of osteomyelitis or osteoarthritis and six of suppurative arthritis alone. The etiologic agents in osteomyelitis or osteoarthritis were Salmonella sp in four cases, Escherichia coli in one, Enterobacter aerogenes in one, Staphylococcus aureus in one, and Haemophilus influenzae type b in one. Five of the cases with infection limited to the joint were caused by Streptococcus pneumoniae; the sixth was caused by H influenzae type b. Fever (greater than or equal to 38.3 degrees C) was present in all children and the temperature was in excess of 39 degrees C in 62%. The mean duration of pain before admission was 4.5 days. The initial total white blood cell count ranged from 5,200 to 29,700/microL (mean 19,436/microL) and the total band neutrophil count ranged from 0 to 5,103/microL (mean 1,660/microL). The ESR was greater than 20 mm/h in eight of the ten patients who were tested. Management consisted of antibiotic therapy in all. Needle aspiration was performed in two patients with osteomyelitis and in three with suppurative arthritis. Incision and drainage was performed in two cases of osteomyelitis and in four with suppurative arthritis. The outcome was satisfactory in all except one patient who had several complications as a consequence of femoral neck osteomyelitis. Recurrence was reported in only one patient.