Frequency and clinical progression of the vitamin E deficiency neurologic disorder in children with prolonged neonatal cholestasis

To determine the frequency of biochemical vitamin E deficiency and of the clinical signs of the vitamin E deficiency neurologic syndrome in children with prolonged neonatal cholestatic disorders, we studied 46 children (aged 1 month to 17.0 years) with chronic forms of intrahepatic neonatal cholestasis and 47 children (aged 4 months to 8.0 years) with extrahepatic biliary atresia. Based on serum vitamin E concentrations and the ratios of serum vitamin E concentration to total serum lipid concentration, 64% of the intrahepatic and 77% of the extrahepatic cholestasis groups were vitamin E deficient. Prior to age 1 year, neurologic function was normal in all children. Between ages 1 and 3 years, neurologic abnormalities were present in approximately 50% of the vitamin E-deficient children; after age 3 years, neurologic abnormalities were present in all vitamin E-deficient children. Areflexia was the first abnormality to develop between ages 1 and 4 years; truncal and limb ataxia, peripheral neuropathy, and ophthalmoplegia developed between ages 3 and 6 years. Neurologic dysfunction progressed to a disabling combination of findings by ages 8 to 10 years in the majority of vitamin E-deficient children. Neurologic function was normal in the vitamin E-sufficient children. We conclude that vitamin E status should be evaluated in infants in whom cholestasis is diagnosed, and effective therapy should be initiated to prevent or treat vitamin E deficiency at an early age.     

Erythrocyte membrane lipid peroxidation before and after vitamin E supplementation in children with cholestasis

In 10 children with chronic cholestasis and without neurologic signs, we evaluated lipid peroxidation and vitamin E levels in serum and in the erythrocytes before and after a therapeutic trial with alpha-tocopherol. We also studied the effects of vitamin E administration on hematocrit and hemoglobin values and on reticulocyte and erythrocyte counts. Plasma and erythrocyte malonyldialdehyde (MDA) values were significantly higher compared with normal control values, whereas plasma and erythrocyte tocopherol measurements were lower. Oral administration of high doses of vitamin E (300 mg/day for 15 days) resulted in lower serum MDA levels, whereas serum vitamin levels did not change significantly. In erythrocytes, the MDA decreased but not to control levels, and vitamin E increased but to lower values than normal. Hematologic values also improved. We conclude that longer treatment might be necessary to completely reverse the oxidative damage associated with vitamin E deficiency in children with cholestasis.     

Neonatal cholestasis as the presenting feature in cystic fibrosis

Between 1960 and 1994 cystic fibrosis was found in nine out of 1474 infants investigated for neonatal cholestasis. Four had delay in passing meconium. In all patients cholestatic jaundice was present during the first 48 hours and in three patients cholestasis was complete, mimicking biliary atresia. Serum cholesterol concentrations were normal in all but two children. Sweat chloride was repeatedly above 95 mmol/l in all instances. Three children had another condition enhancing the risk of cholestasis (alpha1-antitrypsin deficiency, hypopituitarism, perinatal asphyxia, and total parenteral nutrition). Liver histology displayed portal fibrosis and inflammation with bile duct proliferation; mucous plugs in bile ducts were observed in only one patient. Only one child died from cirrhosis. These results indicate that cystic fibrosis is not a major cause of neonatal cholestasis. However early signs of intestinal obstruction and low concentrations of serum cholesterol may indicate cystic fibrosis, regardless of liver histology. Neonatal cholestasis has no prognostic value concerning evolution to cirrhosis.     

Neonatal cholestasis as the presenting feature in cystic fibrosis.

Between 1960 and 1994 cystic fibrosis was found in nine out of 1474 infants investigated for neonatal cholestasis. Four had delay in passing meconium. In all patients cholestatic jaundice was present during the first 48 hours and in three patients cholestasis was complete, mimicking biliary atresia. Serum cholesterol concentrations were normal in all but two children. Sweat chloride was repeatedly above 95 mmol/l in all instances. Three children had another condition enhancing the risk of cholestasis (alpha1-antitrypsin deficiency, hypopituitarism, perinatal asphyxia, and total parenteral nutrition). Liver histology displayed portal fibrosis and inflammation with bile duct proliferation; mucous plugs in bile ducts were observed in only one patient. Only one child died from cirrhosis. These results indicate that cystic fibrosis is not a major cause of neonatal cholestasis. However early signs of intestinal obstruction and low concentrations of serum cholesterol may indicate cystic fibrosis, regardless of liver histology. Neonatal cholestasis has no prognostic value concerning evolution to cirrhosis.     

Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation

Adult-onset type 2 citrullinaemia (CTLN2) is caused by a deficiency of the citrin protein encoded by the SLC25A13 gene. Citrin, an aspartate glutamate carrier in mitochondria, is an essential component of the malate-aspartate NADH shuttle. Recently, citrin deficiency has been reported to manifest as neonatal intrahepatic cholestasis. We report here five cases with neonatal intrahepatic cholestasis caused by citrin deficiency. Genetic diagnosis revealed compound heterozygotes of 851del4/IVS11 + 1G-->A in two patients, IVS11 + 1G-->A/E601X, and IVS11 + 1G-->A/unknown in each one patient and homozygote for S225X in one patient. All cases revealed high levels of alpha-fetoprotein, which are not observed in CTLN2 patients. The condition was self-limiting and spontaneously disappeared after 5-7 months of age in four patients. However, one patient developed hepatic dysfunction from the age of 6 months and required a living-related liver transplantation at the age of 10 months. The patient showed complete recovery after transplantation, and now at the age of 3 years, shows normal growth and mental development. CONCLUSION: we report the first case of neonatal intrahepatic cholestasis caused by citrin deficiency with severe hepatic dysfunction requiring a living-related liver transplantation. Patients with this disorder should be followed up carefully, even during infancy.     

d-Alpha-tocopheryl polyethylene glycol-1000 succinate enhances the absorption of vitamin D in chronic cholestatic liver disease of infancy and childhood.

Rickets and osteopenia, common problems in chronic childhood cholestasis, have been attributed to vitamin D malabsorption leading to reduced serum levels of 25(OH)-vitamin D. d-alpha-Tocopheryl polyethylene glycol-1000 succinate (TPGS), a water-soluble form of vitamin E, forms micelles at low concentration. We evaluated the potential role of TPGS in enhancing vitamin D absorption in eight children (aged 5 mo to 19 y) with severe chronic cholestasis (three extrahepatic biliary atresia, three nonsyndromic intrahepatic cholestasis, and two Alagille syndrome). To evaluate vitamin D absorption, the subjects received vitamin D3 1000 IU/kg (maximum dose of 50,000 IU); they then received the same dose of vitamin D3 mixed with TPGS (25 IU/kg). Serial serum vitamin D3 levels and areas under the curve were measured. All patients had enhanced absorption of vitamin D when it was administered in a mixture with TPGS. Mean area under the curve for serum vitamin D3 was 403.0 +/- 83.1 nmol x h/L (155.6 +/- 32.1 ng x h/mL), with a mean rise above baseline of 13.5 +/- 1.8 nmol/L (5.2 +/- 0.7 ng/mL) with vitamin D/TPGS compared with no rise when vitamin D was given alone (both p less than 0.001). Seven patients have been followed for at least 3 mo while receiving the vitamin D/TPGS combination. Those with initially low serum 25(OH)-vitamin D levels (less than 37.5 nmol/L or 15 ng/mL) had normalization (range 37.5-146 nmol/L) within 1 mo, whereas those with initially normal levels remained normal. While the patients were receiving vitamin D/TPGS, serum vitamin E to total lipid ratio either normalized or remained normal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic value of serum gamma-glutamyl transpeptidase activity in liver diseases in children.

The clinical usefulness of serum gamma-glutamyl transpeptidase (gamma GT) assay for the diagnosis of liver disease in children was assessed retrospectively in 398 children investigated from 1981 to 1986, in whom diagnosis was ascertained according to currently accepted criteria including liver histology in each case. Serum gamma GT activity was within normal limits in 10 controls, in 19 children with portal vein obstruction, and in 10 of 12 children with congenital hepatic fibrosis. Serum gamma GT was raised in all children with biliary atresia, sclerosing cholangitis, paucity of interlobular bile ducts, and alpha 1-antitrypsin deficiency with jaundice. Serum gamma GT was normal in spite of patent clinical signs of cholestasis in 3 patients with benign recurrent intrahepatic cholestasis, 1 infant with post-hemolytic neonatal cholestasis, and in 22 of 28 patients with progressive idiopathic cholestasis akin to Byler disease. In the latter group, children with raised serum gamma GT displayed extensive portal fibrosis and bile duct proliferation on liver histology, while this was not a prominent feature in children with normal serum gamma GT. These results indicate (a) the value and limits of the assay for serum gamma GT activity in children with liver disease, (b) that raised serum gamma GT may be considered a fairly reliable index of bile duct damage, and (c) that serum gamma GT may prove a useful tool in separating two forms of progressive idiopathic cholestasis, with or without bile duct involvement.     

中国4城市2～7岁分析人群维生素B12营养状况流行病学调查

目的了解4城市2～7岁分析人群维生素B12的营养状况。方法2007年5～9月和2008年5～10月,对2 002名2～7岁分析人群进行体格检查、膳食调查、血常规检查及血清维生素B12水平测定,其中重庆市485名、北京市513名、珠海市503名、武汉市501名。结果①2 002名2～7岁分析人群平均维生素B12水平 （ng·L-1）为775±312,市区（835±271）高于郊区（720±338）,P＜0.001;其中重庆市为756±220、北京市为840±414、珠海市为772±245、武汉市为736±317,地区间差异有统计学意义,P＜0.001。②2～7岁分析人群维生素B12水平性别差异不显著,P＞0.05;2～5岁组维生素B12水平随年龄增长呈降低趋势,r=-0.146,P＜0.001;5岁～组和<7岁组维生素B12水平相近。③4城市分析人群维生素B12减少（＜300）检出率为4.7%。其中维生素B12缺乏（＜200）检出率为1.5%,边缘性缺乏（200～300）检出率为3.2%。重庆市、北京市、珠海市和武汉市分析人群血清维生素B12减少检出率分别为2.1%、3.9%、3.2%和9.6%。④分析人群维生素B12水平主要受膳食维生素B12摄入量的影响,P＜0.001。分析人群平均膳食维生素B12摄入量（μg·d-1）市区（2.4±2.0）高于郊区（2.0±1.4 ）,P＜0.05;重庆市、北市京、珠海市和武汉市分析人群平均膳食维生素B12摄入量分别为1.9±1.3、2.8±1.6、2.6±1.8和1.6±1.2,差异有显著统计学意义,P＜0.001。⑤分析人群维生素B12水平与Hb水平呈低度相关,P＜0.001。结论4城市分析人群存在维生素B12减少,以边缘性缺乏为主。儿童维生素B12营养状况受膳食维生素B12摄入量的影响,分析人群血清维生素B12水平何时达到成人水平有待研究。     

Prospective, long-term study of fat-soluble vitamin status in children with cystic fibrosis identified by newborn screen.

OBJECTIVE: To prospectively evaluate the biochemical status of vitamins A, D, and E in children with cystic fibrosis (CF). SUBJECTS: A total of 127 infants identified by the Colorado CF newborn screening program. DESIGN: Vitamin status (serum retinol, 25-hydroxy vitamin D, ratio of alpha-tocopherol/total lipids) and serum albumin were assessed at diagnosis (4 to 8 weeks), ages 6 months, 12 months, and yearly thereafter, to age 10 years. RESULTS: Deficiency of 1 or more vitamins was present in 44 (45.8%) of 96 patients at age 4 to 8 weeks as follows: vitamin A 29.0%, vitamin D 22.5%, and vitamin E 22.8%. Of these patients with initial deficiency, the percent that was deficient at 1 or more subsequent time points, despite supplementation, was vitamin A 11.1%, vitamin D 12.5%, and vitamin E 57.1%. Of the initial patients with vitamin sufficiency, the percent who became deficient at any time during the 10-year period was as follows: vitamin A 4.5%, vitamin D 14.4%, and vitamin E 11.8%. The percent of patients deficient for 1 or more vitamins ranged from 4% to 45% for any given year. CONCLUSIONS: Despite supplementation with standard multivitamins and pancreatic enzymes, the sporadic occurrence of fat-soluble vitamin deficiency and persistent deficiency is relatively common. Frequent and serial monitoring of the serum concentrations of these vitamins is therefore essential in children with CF.     

Comparison of vitamin E and 25-hydroxyvitamin D absorption during childhood cholestasis

To characterize differences in intestinal absorption of fat-soluble vitamins during cholestasis, intestinal absorption of vitamin E was compared with that of 25-hydroxyvitamin D in eight infants and young children with prolonged neonatal cholestasis. Oral tolerance tests were performed using 100 IU/kg/dose dl-alpha-tocopherol and 10 micrograms/kg/dose 25-hydroxyvitamin D. Mean vitamin E absorption was only 1.0% to 1.9% of that of control children, whereas 25-hydroxyvitamin D absorption was 22.5% to 25.1% of that of controls. Although intestinal absorption of both vitamins is impaired during cholestasis, the severity of vitamin E malabsorption far exceeds that of 25-hydroxyvitamin D.     

alpha 1-antitrypsin deficiency in early childhood.

Among 200,000 infants screened for alpha 1-antitrypsin (alpha 1-AT) deficiency, 125 Pi Z, 48 Pi Z, 1Pi S-, and 2 Pi Z- children were followed up prospectively. Eleven percent of the Pi Z infants had neonatal cholestasis, and at 2 years of age three of them had cirrhosis. About 50% of the asymptomatic Pi Z and Pi Z- subjects occasionally had serum alanine aminotransferase (ALAT) levels above normal, and in 15% of them the levels were probably permanently increased during the first two years of life. Two previously healthy Pi Z children had transient symptoms of liver disease at age 2 years in connection with severe infections. The Pi SZ children had no significant clinical liver disease and only two had abnormal serum ALAT levels. Among Pi Z children up to 2 years of age the following diseases were also encountered: eight had recurrent bronchitis with wheezing, two had persistant cough (both had cirrhosis), one had severe pneumonia, one was mentally retarded, three had urinary tract infections, six had pronounced eczema, one had allergic shock, and three had congenital malformations. Among the Pi SZ children one had recurrent bronchitis, one had eczema, and one had juvenile rheumatoid arthritis. Three children, two Pi Z and one Pi SZ, have died. The Pi Z- and Pi S- subjects were healthy. In conclusion a variety of significant symptoms were observed in about 30% of the Pi Z children compared with 6% of the Pi SZ children during the first two years of life.     

The Night Vision Threshold Test (NVTT): a simple instrument for testing dark adaptation in young children

It is estimated that 41 per cent of the population aged under 5 in the developing world has an inadequate vitamin A dietary intake resulting in increased morbidity and mortality. Half a million children go blind each year as a result of vitamin A deficiency. Thirteen and a half million have night blindness, the first sign of vitamin A deficiency. Unfortunately, there is no simple, sensitive and inexpensive means to identify the child who has marginal levels of vitamin A and thus institute means to prevent their development of severe deficiency. A low cost, simple, easy-to-use instrument designed to detect a young child's ability to adapt to darkness was tested in children admitted to the Mwanamugimu Nutrition Unit at Makerere Medical School in Kampala, Uganda. Despite the severe degree of malnutrition found in these children, Night Vision Threshold Test results and serum retinol levels were related (r = 0.41, p < 0.05). Further efficacy trials for this instrument are planned at community sites in Nepal.     

25 Hydroxyvitamin D and vitamin E absorption in healthy children and children with chronic intrahepatic cholestasis

Patients with chronic cholestasis have reduced 25-hydroxyvitamin D (25 OHD) and vitamin E levels. We determined serum concentrations of 25 OHD, 1,25-dihydroxyvitamin D [1,25(OH)₂D] and vitamin E before and after oral administration of 10 g/kg body weight 25-hydroxyvitamin D₃ (25 OHD₃) and 100 IU/kg body weight vitamin E, respectively, in 4 patients with intrahepatic cholestasis and 6 healthy children. Vitamin E increased in all controls but in only one of the four patients. In contrast, oral 25 OHD₃ induced a normal rise in circulating 25 OHD and 1,25(OH)₂D. The low serum levels of 25 OHD in the patients before the oral bolus may have been due to inadequate parenteral vitamin D administration and/or to the simultaneous phenobarbital treatment. The latter possibility is supported by the increase of serum 25 OHD into the normal range after withdrawal of phenobarbital in one of the four patients.We conclude that vitamin E has to be supplemented parenterally or in water-soluble oral form. Further studies are necessary to clarify whether high-dose long-term oral 25 OHD₃ supplementation is sufficient to prevent vitamin D deficiency in patients with chronic cholestasis.Abbreviations 25 OHD 25-hydroxyvitamin D - 25 OHD₃ 25-hydroxyvitamin D₃ - 24,25(OH)₂D 24,25-dihydroxyvitamin D - DBP vitamin D binding protein This report was presented in part at the XIX European Symposium on Calcified Tissues in Stockholm, June 1986. This study was supported by the Deutsche Forschungsgemeinschaft Bu-199-9-1     

Intramuscular vitamin E repletion in children with chronic cholestasis

Progressive spinocerebellar degeneration was identified in six children with chronic cholestatic liver disease and attributed to severe vitamin E deficiency. In addition to areflexia, ataxia, dysmetria, and diminished vibratory and position sense, three patients had pigmentary retinopathy. Abnormalities were present on electromyography, nerve conduction studies, and electroretinography. Because the vitamin E deficiency was not corrected by oral administration of massive doses of vitamin E, vitamin E was administered by the intramuscular route. With doses of 50 to 100 mg of vitamin E every three to seven days, over a 32-month interval (range, 15 to 44 months), vitamin E deficiency and abnormal red blood cell peroxide hemolysis were corrected. Other than discomfort and occasional edema at the site of injection, there were no side effects of parenteral vitamin E therapy. In several other studies intramuscular vitamin E therapy has produced significant neurologic improvement in patients with similar characteristics. In this study clinical progression of spinocerebellar degeneration was arrested but improvement could not be demonstrated despite adequate vitamin E replacement.     

Folinic acid therapy in treatment of dihydropteridine reductase deficiency

We gave folinic acid to three siblings, and to a fourth child, who have or had dihydropteridine reductase (DHPR) deficiency. The youngest began folinic acid therapy in addition to neurotransmitter precursors and a phenylalanine-restricted diet at age 2 months, and at 2 years of age has near normal development without evidence of neurologic impairment. His older brother began similar treatment at 5 1/2 months of age, when early neurologic findings were evident. At age 6 years his mental retardation and neurologic impairment are less severe than reported in most patients with DHPR deficiency. Little improvement occurred in their sister, who first received treatment at 2 years of age, when she already had severe neurologic impairment. An unrelated boy with profound neurologic impairment showed subtle signs of improvement after he began treatment with folinic acid alone at age 9 years. These results provide evidence that folinic acid is important in the treatment of DHPR deficiency and, if begun early in infancy, may prevent irreversible neurologic damage. The mechanism of folinic acid action in DHPR deficiency may be to increase indirectly the synthesis of 5-methyltetrahydrofolate.     

Utility of breath ethane as a noninvasive biomarker of vitamin E status in children.

The purpose of our study was to determine if the ethane content of expired air could be a useful index of vitamin E status in children. Eight children with vitamin E deficiency secondary to chronic severe liver disease were studied: six of these children were treated with parenteral vitamin E (2-5 mg/kg/dose every 4-7 d). Measures of vitamin E status pre- and posttherapy were: serum vitamin E, 2 +/- 1 versus 7 +/- 1 micrograms/mL (p less than 0.001); serum vitamin E:total lipids, 0.3 +/- 0.1 versus 1.0 +/- 0.1 mg/g (p less than 0.001); and erythrocyte peroxide hemolysis test, 80 +/- 10 versus 6 +/- 12% (p less than 0.001). Fasting breath ethane in the patients pre- and posttherapy was 78 +/- 10 versus 31 +/- 11 pmol/kg/min (p less than 0.001). Breath ethane correlated negatively with serum vitamin E (p less than 0.042) and serum E:total lipids (p less than 0.004) and positively with the erythrocyte peroxide hemolysis test (p less than 0.003). Values for treated patients did not differ from those for fasted sibling controls (34 +/- 12 pmol/kg/min), postprandial sibling controls (31 +/- 12 pmol/kg/min), and healthy children sampled randomly, in the nonfasted state (21 +/- 14 pmol/kg/min). Breath ethane production in one patient (up to 168 pmol/kg/min) did not normalize after treatment of vitamin E deficiency until her selenium deficiency was corrected as well. We conclude that this noninvasive test can be useful as a screen for vitamin E deficiency in children and for ascertaining response to therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Progressive familial intrahepatic cholestasis and hereditary anomalies lf hepatocellular metabolism of bile acids]

Progressive familial intrahepatic cholestasis (PFIC), also known as Byler disease, is an inherited cholestasis of hepatocellular origin which is characterized by cholestasis presenting often in the neonatal period leading to death due to liver failure at ages ranging from infancy to adolescence. The pattern of appearance of affected children within families is consistent with autosomal recessive inheritance. The etiology is poorly understood but several studies have recently provided support for an heterogeneity with at least three subcategories among the spectrum of PFIC. The first subtype is characterized by an early onset, often during the neonatal period, a severe pruritus, normal serum gamma-glutamyltransferase (GGT) activity and cholesterol level, high concentration of serum primary bile acids, absence or very low levels of primary bile acids, absence or very low levels of primary bile acids in bile, and absence of ductular proliferation on standard optical liver histology. Its leads to death due to liver failure within a few years, rarely after adolescence. It is possibly due to an inborn error in primary bile acid secretion and recently, a locus for this subtype has been mapped in the original Byler pedigree to 18q21-q22, the benign recurrent intrahepatic cholestasis region. In the second subtype, affected children exhibit also normal serum GGT activity and cholesterol level and absence of ductular proliferation, but have no pruritus and only traces of primary bile acids in serum. An inborn error in primary bile acid synthesis has been demonstrated in this subtype. The third subtype presents later in life, carries a higher risk of portal hypertension and gastrointestinal bleeding and ends in liver failure at a later age. It is characterized by a mild and unconstant pruritus, high GGT serum activity, moderately raised concentrations of serum primary bile acids, normal concentration of biliary primary bile acids, and ductular proliferation and inflammatory infiltrate with patency of intra and extrahepatic bile ducts. An abnormal expression of the MDR3 gene is involved. A fair proportion of children affected with all subtypes of PFIC may benefit from oral bile acid therapy. In some cases partial external biliary diversion or liver transplantation should be proposed.     

Monitoring of 25-OH vitamin D levels in children with cystic fibrosis

BACKGROUND: Patients with cystic fibrosis are at risk for malabsorption of fat-soluble vitamins, and those with low 25-OH vitamin D levels have a higher risk of low bone mineral density and long-term skeletal complications. It is currently recommended that vitamins A and E be monitored yearly; however, no recommendations exist for 25-OH vitamin D. Because all three vitamins are fat-soluble, the hypothesis in the current study was that low levels of vitamins A and E could identify patients at risk for low 25-OH vitamin D, so that 25-OH vitamin D measurements could be obtained in only selected circumstances. METHODS: Forty (21 girls) patients with CF, age 10.5 +/- 3.9 (SD) years, were assessed in a cross-sectional survey for ideal weight for height (percentage of predicted), spirometry (percentage of predicted FEV1, 33/40 patients), and serum levels of vitamins A, E, 25-OH vitamin D, and cholesterol (37/40 patients). RESULTS: Nine (22.5%) of 40 patients were malnourished (percentage of predicted ideal weight for height <85%), 7 (21.2%) of 33 had moderate to severe lung disease (FEV1 <60%), 4 (10%) of 40 had low levels of vitamin A, 3 (7.5%) of 40 had low vitamin E levels, 4 (10.8%) of 37 low vitamin E/cholesterol levels, and 4 (10%) of 40 had marginal or low levels of 25-OH vitamin D (<40 mmol/l). The patients with low 25-OH vitamin D were older, with no child < 12 years of age having a 25-OH vitamin D level less than 40 mmol/l. They also had lower vitamin E and vitamin E/cholesterol levels than those with normal 25-OH vitamin D levels. The groups did not differ in percentage of predicted ideal weight for height, lung function, or vitamin A levels. The best positive predictor for 25-OH vitamin D less than 40 mmol/l was low vitamin E (66.7%), with a negative predictive value of 94.6%. 25-OH vitamin D levels correlated with vitamin E/cholesterol levels (r = 0.41, P < 0.01) and weakly with vitamin E levels (r = 0.28, P < 0.08), but not with vitamin A levels. CONCLUSIONS: These results suggest that children aged less than 12 years and older children with normal vitamin E levels are especially unlikely to have low 25-OH vitamin D levels, and this measure can therefore be omitted. In contrast, those children with low vitamin E levels may warrant monitoring.     

Hepatitis and cholestasis in infancy: clinical and nutritional aspects

A major complication of cholestasis is fat malabsorption related to decreased intestinal bile acids, which leads to malnutrition and fat-soluble vitamin deficiency. The impaired excretion of bile acids leads to a low intraluminal micellar concentration that causes long-chain triglyceride lipolysis and absorption to be ineffective. Medium-chain triglycerides (MCTs) are more readily absorbed when there are low concentrations of bile acids and therefore are a good source of fat calories; MCTs can be administered as MCT-containing formulas. In those children who are unable to take sufficient calories by mouth, it is important to start nocturnal enteral feeding to improve nutritional status. In infants with cholestasis, the absorption of fat-soluble vitamins (A, D, E and K) that require bile acids is also impaired, and supplementation is mandatory. Vitamin K deficiency may be responsible for hypoprothrombinaemia, which may lead to bleeding diathesis, Vitamin K (phytomenadione) should therefore be promptly administered intravenously, at a dose of 1 mg. Chronic vitamin E (alpha-tocopherol) deficiency is associated with a progressive neuromuscular syndrome that can cause cerebellar ataxia, areflexia and peripheral neuropathy. Supplements are given orally in doses of 3-5 times the normal requirement if cholestasis is incomplete. In complete cholestasis, supplements must be given intramuscularly at monthly intervals. In infants who fail to thrive, dietary supplements of carbohydrate polymers and MCTs are required.