Hartnup disease masked by kwashiorkor.

This report describes an 11-month old girl with Hartnup disease presenting with kwashiorkor and acrodermatitis enteropathica-like skin lesions but free of other clinical findings. This case with kwashiorkor had acrodermatitis enteropathica-like desquamative skin eruption. Since zinc level was in the normal range, investigation for a metabolic disorder was considered, and Hartnup disease was diagnosed.

Prevalence of aflatoxins in blood and urine of Egyptian infants with protein-energy malnutrition.

The aim of the present work was to study the presence of aflatoxins in blood and urine of infants with protein-energy malnutrition (PEM). The study was conducted on 60 infants, 30 with kwashiorkor and 30 with marasmus, with 10 age-matched healthy infants studied as a control group. Complete blood count, liver function tests, and determination of the level of aflatoxins (B1, B2, G1, G2, M1, M2, G2a, B3, GM1, P, and aflatoxicol R0) in blood and urine were carried out in all studied infants. Serum aflatoxins were detected in more infants with kwashiorkor (80%) than in those with marasmus (46.7%). The mean serum levels of total aflatoxins, AFB1, AFG1, and AFB2a, were significantly higher in infants with kwashiorkor (p <.001). Aflatoxin B1 (AFB1) was the most commonly detected type. The prevalence of aflatoxin excretion in the urine of infants with kwashiorkor was 80%, a higher value than that in infants with marasmus (46.7%). The mean urinary concentration of total aflatoxins followed the same pattern of distribution (p < .052). There were no significant differences between groups in the mean urinary concentrations of AFB1, AFG1, AFB2a, AFM1, and AFG2a. Aflatoxins were not detected in any of the serum or urine samples of the control group. Aflatoxins are highly prevalent in this study population and show a high degree of correlation with severe PEM.

Prediction of nutritional status by chemical analysis of urine and anthropometric methods.

A combination of anthropometric and chemical indices was used to investigate the nutritional status of 26 healthy (H) and kwashiorkor (K) children aged 2-5 years and possibly predict the onset of malnutrition. The healthy children had significantly (p>0.05) higher values for weight, height, middle upper arm circumference and weight/height ratio than kwashiorkor children. The healthy children had significantly higher urinary concentrations of urea, inorganic sulphate and sulphate relative to creatinine, but significantly lower thiocyanate and thiocyanate relative to creatinine than the kwashiorkor children. The results of the present study would tend to indicate that a chemical analysis especially of urea, inorganic sulphate or thiocyanate alone or the urea/creatinine, inorganic sulphate/creatinine or thiocynate/creatinine ratio could be used to predict malnutrition after the initial anthropometric measurements. This study should however be repeated with a large population of volunteers to determine the specific cut-off points for each anthropometric and chemical analysis.

Increased oxidative stress in kwashiorkor.

To test the hypothesis that kwashiorkor is associated with increased oxidative stress, urinary concentrations of 2 oxidized amino acids, o,o '-dityrosine and ortho -tyrosine, were measured by gas chromatography-mass spectrometry. Children with kwashiorkor, with or without infection, had a 3- to 7-fold increase in urinary o,o '-dityrosine and a 1.5- to 2-fold increase in ortho -tyrosine when compared with well-nourished children. This observation raises the possibility that oxidative damage to proteins and other biologic targets plays a role in the clinical manifestations of kwashiorkor.

Lysosomal enzymuria in protein energy malnutrition.

Protein energy malnutrition (PEM) is common in underprivileged populations in many parts of the world and results from diets deficient in protein (kwashiorkor) or protein and calories (marasmus). The literature documents renal tubular abnormalities in children with PEM. In PEM the reabsorption of amino acids and phosphate is defective. In many kidney disorders in which renal tubular function is impaired (e.g., diabetes, preeclampsia, nephrotic syndrome, sickle cell anemia), lysosomal enzymuria ensues. We compared the urinary excretion of the following five lysosomal enzymes in 31 Nigerian children with marasmus, kwashiorkor, or marasmic-kwashiorkor: beta-hexosaminidase, alpha-galactosidase, beta-galactosidase, beta-glucuronidase, and alpha-mannosidase. All of the protein energy malnourished children and the 18 age- and gender-matched controls were from the city of Jos, located in central Nigeria. In the severely malnourished children, the urine levels of all five lysosomal enzymes (expressed as units of enzyme activity per mg creatinine) were markedly increased. The greatest increases were seen with beta-hexosaminidase (16-fold) and beta-glucuronidase (14-fold). Routine clinical analyses also revealed that, relative to the control population, the sera of the 14 most severely malnourished patients contained 2- to 5-fold more vitamin B12 and markedly reduced levels (15%, p < 0.00001) of calcium. These data are significant in that they document lysosomal enzymuria in Nigerian children with severe PEM and point to the potential diagnostic utility of the urinary beta-galactosidase determination for assessing renal function in children with this disorder.

Bone turnover in malnourished children.

Pyridinoline (PYD) and deoxypyridinoline (DPD) are cross-linking aminoacids of collagen that are located mainly in bone and cartilage. When bone matrix is resorbed these cross-links are quantitatively excreted in the urine and therefore represent specific markers. We have measured the urinary excretion rate of PYD and DPD in 46 severely malnourished boys to assess their skeletal turnover and to relate this to their subsequent rate of growth. The children were aged 13 months (SD 6), and height-for-age was -3.6 (1.6) Z-score, and weight-for-height was -2.4 (0.8) Z-score. PYD excretion when malnourished and after "recovery" was 11.2 (4.6) nmol h-1m-2 and 32.2 (10.8) nmol h-1m-2 and DPD excretion was 2.6 (1.3) nmol h-1m-2 and 7.5 (3.0) nmol h-1m-2, respectively. The ratio of the two cross-links did not change with recovery. These data show that cartilage and bone turnover is much lower in the malnourished than in the recovered child. There was no difference in the degree of depression of turnover between the children with marasmus, marasmic-kwashiorkor, or kwashiorkor. The rate of height gain during recovery was significantly related to cross-link excretion, age, and weight-for-height on admission. These three factors accounted for 44% of the variance in the height velocity of the children. PYD and DPD excretion rate could be used to assess therapeutic interventions designed to alleviate stunting.

PIP: The Tropical Metabolism Research Unit at the University of the West Indies in Jamaica made anthropometric measurements of 46 13-month-old male infants to assess changes in bone resorption during malnutrition by measuring the urinary excretion rate of pyridinoline (PYD) and deoxypyridinoline (DPD) and to determine whether bone turnover is associated with recovery. Unit staff used standard methods to treat the malnourished boys, including an energy dense diet (cow's milk formulated from Perlargon and corn or coconut oil). Before treatment, their height-for-age stood at -3.6 Z-score and their weight-for-height was -2.4 Z-score. The rate of excretion of PYD and DPD in malnourished children was only about 33% of that after they recovered (11.2 nmol per hour per sq. meter vs. 32.2 nmol per hour per sq. meter and 2.6 nmol vs. 7.5 nmol per hour per sq. meter, respectively; p .001). Therefore, cartilage and bone turnover was considerably lower in the children when they were malnourished than when they recovered. Recovery did not alter the ratio of these 2 cross-link amino acids, however, suggesting that changes in endochondral growth relative to bone remodelling did not occur. The extent of depression in bone turnover was basically the same between children with marasmus, marasmic-kwashiorkor, or kwashiorkor. The rate of height gain of the children during recovery from malnutrition was significantly associated with age (p .001), PYD excretion at admission (p = .003), and weight-for-height at admission (p = .01), all 3 of which explained 44% of the variance in the rate of height gain of the children. Since this study demonstrated that PYD and DPD are associated with longitudinal growth in children recovering from malnutrition, more research on the effect of dietary manipulation on longitudinal growth should be done, which should define requirements for longitudinal growth and identify needed steps to prevent stunting.

Aflatoxin exposure and its relationship to kwashiorkor in African children.

The urinary excretion of aflatoxins in normal children from a periurban area, as well as those hospitalized with kwashiorkor and marasmus was assessed. In no case was aflatoxin isolated from the urine. It is concluded that aflatoxin exposure is unusual in this population and that aflatoxins do not play a primary role in the pathogenesis of kwashiorkor.

Aflatoxin excretion in children with kwashiorkor or marasmic kwashiorkor--a clinical investigation.

A group of five children with kwashiorkor, seven with marasmic kwashiorkor and one underweight child were given an aflatoxin-free diet consisting of maize meal and milk powder. Blood specimens were collected on admission; on day 4 and 10, 24 hour urine and stool samples were collected for the first ten days. Serum, urine and stool samples were analysed for aflatoxins using high performance liquid chromatography with fluorescent detection, after various extraction and clean-up procedures. The children with kwashiorkor and marasmic kwashiorkor excreted aflatoxins in stools for up to 9 and 6 days after admission respectively. No aflatoxins were detected in the stools or urine of the underweight child. In kwashiorkor, urinary excretion ceased after 2 days, while in marasmic kwashiorkor urinary excretion persisted for 4 days. In stools, B1 was the type of aflatoxin detected most frequently in kwashiorkor and least frequently in marasmic kwashiorkor. Aflatoxin M2 was frequently detected in the stools of both groups of children. Estimates of the total amount of aflatoxin excreted by kwashiorkor and marasmic kwashiorkor indicate that these children were harbouring up to 4 micrograms/kg body weight at the time of admission. These findings establish that aflatoxins accumulate in body fluids and tissues in kwashiorkor and marasmic kwashiorkor which is only slowly eliminated.

Aflatoxins and kwashiorkor in Kenya: a hospital based study in a rural area of Kenya.

Aflatoxin analyses were undertaken on sera and urines of 41 children admitted to a rural hospital in Kenya with kwashiorkor, marasmus, marasmic kwashiorkor or normal nutrition (Wellcome Classification). Aflatoxins were detected most frequently and at highest concentrations in the sera of kwashiorkors who, conversely, showed aflatoxins least frequently in their urine and in concentrations that were disproportionately low compared with serum/urine aflatoxin levels in other groups. These findings indicate altered aflatoxin metabolism in kwashiorkor and support the hypothesis that there are special relationships between aflatoxins and kwashiorkor.

Aflatoxins and kwashiorkor: clinical studies in Sudanese children.

Aflatoxin analysis of blood and urine by high performance liquid chromatography in 584 Sudanese children is reported. The results in 404 malnourished children comprising 141 kwashiorkor, 111 marasmic kwashiorkor and 152 with marasmus are compared with 180 age-matched controls and correlated with clinical findings. The aflatoxin detection rate and mean concentration were higher in serum of children with kwashiorkor than the other groups. The difference between the detection rate in kwashiorkor and controls was significant (p less than 0.05). The aflatoxin detection rate in urine was highest in the marasmic kwashiorkor group and the mean concentration was higher in the marasmic kwashiorkor and marasmic groups than in the kwashiorkor and control groups. There were important differences in the detection of certain aflatoxins between the groups. Aflatoxicol was detected in the sera of 16 (11.6%) kwashiorkor, in six (6.1%) marasmic kwashiorkor, but in none of the controls and only once in marasmus. These differences are highly significant (p less than 0.0001). The ratio of AFB1 to AFM1 was higher in the sera and urines of kwashiorkors than in controls, suggesting that the normal transformation of AFB1 to AFM1 may be impaired in kwashiorkor with consequent increase in transformation of AFB1 to aflatoxicol. The study therefore provides evidence of differences in the metabolism of aflatoxins in children with kwashiorkor compared with children with other forms of malnutrition and normally nourished children and confirms the association between aflatoxins and kwashiorkor contained in a preliminary report on this work.

Urinary free amino acids pattern in protein-energy malnourished Sudanese children.

The urinary free amino acid pattern in a morning urine sample of Sudanese children suffering from Kwashiorkor and marasmus were determined before and during the course of treatment up to the 2nd week. The urinary amino acid/total urinary N (3.62) was found to be almost constant for Kwashiorkor patients, while the mean for marasmic patients was found to be 27. The concentration of leucine, valine, phenylalanine, methylhistidine, lysine, hydroxylysine and beta-amino-isobutyric acid was elevated in marasmic children, while the concentration of most of these amino acids was at a lower level in Kwashiorkor patients. The significance of these differences was discussed in relation to the biochemical detection of these deficiencies in field nutrition surveys.

Renal function in protein-energy malnutrition.

So far, most studies on renal function in children with advanced protein-energy malnutrition have shown an impairment of glomerular filtration rate and renal plasma flow, as well as diminished ability to excrete an acid load and a concentrated urine. Investigation of these functions in eight marasmic infants and eight children with kwashiorkor once they were free of obvious infections and acute electrolyte disturbances has shown a practically normal renal performance.

[Urinary excresion of indican during recovery from malnutrition]. / Excreción urinaria de indicán durante la recuperación de la desnutrición.

Most indican excreted in the urine comes from the degradation of tryptophan through the action of microorganisms dwelling within the intestinal lumen. Based on this knowledge, the excretion of this compound was investigated during the recovery process of 19 malnourished infants; thus, attempts were made to recognize indirectly whether quantitative modifications take place in the intestinal flora as the state of nutrition is re-established. The results do not suggest the presence of an important variation of the bacterial content within the intestine of these children, at least during the first four weeks of their recovery.

[Evaluation of the urinary and plasma urea ratio and osmolarity in newborn infants and malnourished children with pathological and normal renal function]. / Valoración de la relación urinaria/plasmática de urea y osmolaridad en recién nacidos y desnutridos avanzados con función renal normal y patológica

Previous evaluation of diagnostic tests for acute renal failure in children demonstrated that osmolality urine/plasms (U/P) ratio below 1.3, urea ratio below 4.8 and a negative mannitol test (absence of a diurteic response within one hour after intravenous administration of 60 ml/m2 of 12.5% mannitol solution) may be considered as valuable factors in this diagnosis. However, the validity of those ratios were in doubt in selected populations such as newborns and in severe malnourished children in whom an impairment in concentrating urine capacity can be anticipated. With the purpose to test the validity of these parameters, a group of 53 newborns and 68 children with severe malnutrition were studied. They were admitted to the hospital with dehydration secondary to acute diarrhea presenting oliguria and hyperpnea and before any treatment was given, urine and blood samples were taken to determine urea and osmolality U/P ratios besides routine chemistries. Mannitol test was performed when urine could not be obtained and in some cases in whom U/P results deserved confirmation with the biological test. Seven of the 53 newborn patients developed acute renal failure with negative mannitol test and further clinical course of persistent oliguria. Urea and osmolality U/P ratios were 3.0 +/- 1.5 and 1.07 +/- 0.01 respectively, whereas the remaining 46 newborns had afterwards an uneventful recovery presenting U/P ratios of 12.4 +/- 8.5 for urea and 1.32 +/- 0.57 for osmolality. The difference between the average values of urea U/P ratio of the patients with acute renal failure and those with functional oliguria, were statistically significant at the level of p less than 0.01, but there was no significant difference between osmolality ratio values.

Bicarbonate excretion in kwashiorkor.

Children with kwashiorkor have an impairment of bicarbonate excretion which may result in the inappropriate production of acid urine in the presence of systemic alkalosis. This defect has resolved after 2 weeks of treatment.