Lipid myopathy associated with renal tubular acidosis and spastic diplegia in two brothers.

Lipid myopathy is a group of disorders involving mitochondrial fatty acid oxidation. We describe two brothers, 3 years 8 months old and 2 years 9 months old, respectively, with progressive spastic diplegia, developmental delay, failure to thrive, and chronic metabolic acidosis who had lipid myopathy and renal tubular acidosis. Brain magnetic resonance imaging revealed demyelinating changes in the periventricular white matter, which was compatible with spastic diplegia. These symptoms may be related to errors in fatty acid metabolism. Cerebral palsy had been misdiagnosed in both of these patients at another hospital. Therefore, for patients with late-onset and progressive spastic diplegia, detailed investigations for underlying diseases are warranted.

Nephromegaly and elevated plasma hepatocyte growth factor-transforming growth factor-beta1 ratio in infants with fulminant hepatitis or biliary atresia.

Nephromegaly, assessed by calculating kidney volume using renal ultrasound, was studied in infants with biliary atresia, neonatal hepatitis, or fulminant hepatitis. We evaluated kidney volume in 29 patients with biliary atresia, 17 patients with neonatal hepatitis, and 10 patients with fulminant hepatitis, as well as 32 healthy infants. Levels of plasma hepatocyte growth factor (HGF) were measured in all infants. Levels of plasma transforming growth factor-beta1 (TGF-beta1) were also measured in diseased infants and 20 healthy infants. Significant nephromegaly was found in infants with biliary atresia compared with healthy infants (P < 0.001 by analysis of covariance). Marked nephromegaly was also noted in all infants with fulminant hepatitis and 35% of infants with neonatal hepatitis. No nephromegaly was found in infants at 2 months of age with biliary atresia or neonatal hepatitis despite mildly elevated plasma HGF levels. Regardless of the duration of HGF exposure and healthy renal growth by a certain age, a positive correlation existed between plasma HGF level and kidney volume (r = 0.529; P < 0.001), but an inverse correlation was found between plasma TGF-beta1 level and nephromegaly (r = -0.505; P < 0.001) in all diseased infants. There was a stronger positive correlation between plasma HGF-TGF-beta1 ratio and kidney volume (r = 0.666; P < 0.001) and degree of nephromegaly (r = 0.717; P < 0.001). These results confirm the presence of large kidneys not only in patients with biliary atresia but also in patients with fulminant hepatitis, which suggests the possible pathogenic role of HGF and manifests as elevated HGF-TGF-beta1 ratios in patients with such conditions. Nephromegaly in patients with severe or chronic liver dysfunction may provide a new in vivo model to study the mechanisms of renal growth.

Paraganglioma manifesting as shock: a case report.

Paraganglioma is a rare neuroendocrine tumor in children that rarely manifests as shock. We describe the case of a 12-year-old girl with paraganglioma who developed impaired cardiac function, pulmonary edema, and shock at the time of admission. Her blood pressure stabilized after intravenous normal saline rescue and dopamine treatment. However, hypertension was noted thereafter. After a series of examinations, paraganglioma was diagnosed and excision of the tumor was performed. After surgery, blood pressure stabilized and her cardiac function had fully recovered at 4 months' follow-up.

Renal malformations in children with Turner's syndrome.

Between 1988 and 1999, renal sonography and intravenous urography were performed to detect renal malformations in 54 patients with Turner's syndrome (TS). The mean age of these patients at diagnosis of TS was 9.2 +/- 4.6 years. Renal malformations were detected in 21 patients by intravenous urography and there was no significant difference in the frequency of renal malformations among different karyotype groups. Horseshoe kidney was the most common renal malformation, followed by duplex kidney. Fifteen of 21 renal malformations were not detected by renal sonography. We conclude that these TS patients had a high frequency of renal malformations, and that the detection rate of horseshoe kidney and duplex kidney by renal sonography was not satisfactory. Although renal sonography alone can be used to detect more severe renal malformations that may need further management, it may underestimate the frequency of renal malformation in children with TS.

Hypovolemia and hypovolemic shock in children with nephrotic syndrome.

Hypovolemic shock is not an uncommon presentation in nephrotic syndrome, yet it is seldom mentioned in the literature. This study was performed to investigate the prevalence of hypovolemia and hypovolemic shock in the acute nephrotic stage, and the association of hemoconcentration and abdominal pain with hypovolemic status. Two hundred and twenty-five patients with a total of 328 admissions to the pediatric ward of our hospital during 1983 to 1996 were retrospectively reviewed for hypovolemic episodes. Clinical presentation and laboratory data including hemoglobin, serum sodium, albumin, cholesterol, and triglyceride levels were investigated. Thirteen patients with 19 episodes (5.8%) of hypovolemic shock were found, and had more severe hemoconcentration (hemoglobin 19.6 +/- 2.2 g/dL) and hyponatremia (127.3 +/- 7.2 mEq/L). Another 33 patients with 41 symptomatic hypovolemic episodes without hypotension (12.5%) were found, and their hemoglobin levels were higher compared to patients without hypovolemic symptoms. Among 61 episodes of abdominal pain and hemoconcentration, 58 were responsive to albumin infusion. This suggested the presence of hypovolemia. Twenty patients had abdominal pain without hemoconcentration, and 18 of them had primary peritonitis. Hypovolemia was found in patients at the acute nephrotic stage, and was usually associated with hemoconcentration and abdominal pain. A combined examination of hemoglobin and serum sodium is the best indicator of hypovolemic status. Both primary peritonitis and hypovolemic episodes should be taken into consideration when managing abdominal pain in children with nephrotic syndrome.

Nephrotic syndrome in a bone marrow transplant recipient without chronic graft-versus-host disease.

A 5-year-old girl developed severe proteinuria and microscopic hematuria 17 months after allogeneic bone marrow transplantation (BMT) for chronic myeloid leukemia. These nephrotic symptoms occurred during cyclosporin tapering, in the absence of other signs of chronic graft-versus-host disease (GVHD). A renal biopsy revealed focal segmental glomerulosclerosis. After methylprednisolone therapy, the proteinuria gradually decreased. The altered or disordered immune regulation that occurred after BMT may have resulted in the development of nephrotic syndrome.

Mitochondrial cytopathy combined with Fanconi's syndrome.

Severe muscle weakness in Fanconi's syndrome is rarely the result of mitochondrial cytopathy. We describe a rare case of a 9-year-old male with early onset of Fanconi's syndrome. He developed severe proximal muscle weakness exacerbated by hypokalemia and hypophosphatemia in childhood. The muscle biopsy revealed increased accumulation of abnormal mitochondria and fat droplets in histochemical stains and electron microscopy. Mitochondrial cytopathy cannot be excluded in Fanconi's syndrome with late onset of muscular impairment. Long-term follow-up of his clinical course is suggested to understand the natural history of this unusual case.

Epidermal nevus syndrome with hypermelanosis and chronic hyponatremia.

Epidermal nevus syndrome is seldom encountered, and its association with hypermelanosis and the chronic syndrome of inappropriate antidiuretic hormone secretion (SIADH) has never been reported. A male neonate who developed intractable seizures and hyponatremia soon after birth is reported. He had alopecic patches on the scalp at birth. Large areas of skin hyperpigmentation, and epidermal nevi developed gradually. The clinical picture of hypotonic hyponatremia, high urine osmolality, elevated urine sodium, and euvolemia was compatible with SIADH. The seizures did not correlate with the hyponatremia, and no other cause for the seizures could be identified. The hyponatremia became chronic and was treated with a direct supply of sodium chloride. The development of the patient was markedly delayed at the last visit when he was 1 year of age. It is suggested that hypermelanosis and chronic SIADH may also be a variant presentation of epidermal nevus syndrome.

Secondary hypertension in children.

Secondary hypertension is a potentially curable disease. One-hundred-and thirty six children was diagnosed as hypertension in the National Taiwan University Hospital from January 1992 to June 1998 and they were retrospectively reviewed and analysed for the etiological factors, presentation, and clinical outcome. The most common cause of hypertension was coarctation of aorta in infants and systemic lupus nephritis in adolescents. These children often presented symptoms and signs not directly related hypertension (37.5%). Twenty eight children (20.6%) died. The hypertension of the survival had been controlled by surgery, chronic hemodialysis, or medication.

Nephrocalcinosis in childhood.

Charts of 16 children with nephrocalcinosis between 1990 and 1997 were reviewed. The cause of nephrocalcinosis was believed to be iatrogenic in 7 patients (43.8%) and non-iatrogenic in 9 (56.2%). Vitamin D therapy was responsible for 5 patients of iatrogenic nephrocalcinosis, and furosemide therapy for the remaining iatrogenic patients. Non-iatrogenic cases consisted of 3 patients with renal tubular acidosis, 3 patients with idiopathic hypercalciuria, and the 3 other patients with rare underlying conditions. Abdominal X-ray detected nephrocalcinosis in only 2 (12.5%) of the total 16 patients. None showed resolution of nephrocalcinosis during these years of follow-up.

Sonographic measurements of renal size in normal children and children with compensatory renal hypertrophy.

Renal length and anteroposterior diameter of both kidneys were measured from normal renal sonograms of 326 children (aged from newborn to 15 years) and graphed to provide a growth chart of normal renal size against age. Mean renal lengths are reported for each year of age. The renal size of 20 children with single kidney, either congenital or postnephrectomy, were also evaluated. Our data showed actual nephromegaly of the solitary kidney indicating compensatory renal growth.

Clinical observations of erythema multiforme in children.

Erythema multiforme (EM), a cutaneous or mucocutaneous disorder, occurs primarily in young adults. To evaluate the precipitating factors, clinical courses, and treatment of this disease in children, 30 cases aged from 1 month old to 15 years of age were studied retrospectively from Jan 1988 to Aug 1998. Twenty-three cases were diagnosed as minor type; the other 7 were of major type (Stevens-Johnson syndrome). Mycoplasma infection was identified in 4 patients, and adenovirus in one patient with EM minor. Cytomegalovirus was found in one EM major patient. Anticonvulsant administration before the skin lesions were recorded in 5 EM major patients and 2 EM minor patients. All cases received supportive treatment during admission. Besides, 6 of 7 patients with EM major, and 11 of 23 EM minor (Group A) received systemic corticosteroid at a dose equal to prednisolone 1-2 mg/kg/day for 3-14 days. One EM major patient and 11 patients with EM minor (Group B) received supportive care only. One EM minor patient with acute idiopathic thrombocytopenia purpura was treated with intravenous immunoglobulin. The mean duration of course of EM minor was 11.8 +/- 2.9 days, and it was 25.1 +/- 9.8 days for EM major. No mortality and no sequelae were noted. The average disease course and hospitalization time were not significantly different between Group A and B: (11.4 +/- 3.1 days vs 12.4 +/- 2.9 days, p = 0.45); (5.4 +/- 2.0 days vs 6.3 +/- 3.1 days, p = 0.47). This study demonstrated that infections, especially mycoplasma, and anticonvulsants play important roles in childhood EM. The skin lesions of EM minor subsided within 2 weeks, and EM major recovered completely within 6 weeks. Systemic corticosteroid may be beneficial to EM major, but probably is unnecessary for patients with EM minor.

Urinary endothelin-1 in children with acute renal failure of tubular origin.

To understand the changes of urinary endothelin-1 (ET-1) concentrations in acute renal failure (ARF) and to investigate the origin of human urinary ET-1, we studied urinary ET-1 excretion in 70 normal children and 12 children with ARF caused by tubular dysfunction. Urinary ET-1 excretion was expressed as a ratio of urinary ET-1 to urinary creatinine (ET-1/Cr). Among healthy children, the highest urinary ET-1/Cr values were found during infancy. In patients with ARF, there was a positive correlation between urinary ET-1/Cr values and daily total urinary ET-1 (r = 0.42, n = 26, p < 0.05). Plasma ET-1 concentrations were elevated in children with ARF during the period of peak serum creatinine concentration. During the course of ARF, the lowest urinary ET-1/Cr value occurred during the period of peak serum creatinine, whereas the plasma ET-1 concentration declined after the peak. These results provide insight into the developmental changes of urinary ET-1 values in normal children, and illustrate the pattern of changes in plasma and urinary ET-1 concentrations during the course of ARF in children. The results suggest that renal production, rather than clearance from the circulation by glomerular filtration, may be the source of urinary ET-1.

Urinary endothelin-1 in children with glomerulonephritis.

Urinary endothelin-1 (ET-1) excretion was studied in 28 children with glomerulonephritis. Urinary ET-1 excretion was expressed as a ratio of urinary ET-1 to urinary creatinine (ET-1/Cr). There was a positive correlation between urinary ET-1/Cr and daily total urinary ET-1 in patients (r = 0.65, n = 32, p < 0.001). Urinary ET-1/Cr in children with glomerulonephritis and normal renal function was not different from that of normal controls. Urinary ET-1/Cr in glomerulonephritis children with ARF was lowest. These results showed that the pattern of urinary ET-1/Cr varied depending on the state of renal function in children with glomerulonephritis.

Correlation between urinary epidermal growth factor excretion and serum thyroid hormone in premature and term neonates.

Eighty neonates, including 14 full-term, 31 premature, 27 twin or triplet, 6 small-for-gestational-age, and 2 infants with hyperthyroidism, were evaluated. The urinary epidermal growth factor/creatinine ratio (EGF/Cr) on the 1st postnatal day was not statistically different among full-term, premature, multiple-pregnancy, and small-for-gestational-age infants (F = 1.06, p = 0.6). There was no difference in urinary EGF/Cr between the 1st postnatal day and the 7th day (p = 0.4 by paired t test). The urinary EGF/Cr was not correlated with the serum thyroid-stimulating hormone level (r = -0.162, n = 60, p = 0.21), but showed a positive correlation with serum total T3 (r = 0.526, n = 60, p < 0.001) and with serum total T4 (r = 0.460, n = 60, p < 0.001). The correlation between urinary EGF/Cr and serum free T4 was even much better (r = 0.727, n = 25, p < 0.001). These results implicate that thyroid hormone may play a role in regulating urinary EGF excretion.

Urinary bladder outlet obstruction in children.

Bladder outlet obstruction, either functionally or structurally, could lead to bladder trabeculation, vesicoureteric reflux, hydronephrosis and, eventually, to renal parenchymal damage. If no treatment is given, end-stage renal failure will ensue. The cases of 17 patients of bladder outlet obstruction at National Taiwan University Hospital from 1984 to 1997 were reviewed. Initial presentation, etiology and treatment were discussed. Nine patients were victims of neurogenic bladder and two patients were victims of nonneurogenic neurogenic bladder. Four patients suffered from posterior urethral valve. Ureterocele and urethral rhabdomyosarcoma were noted in one case each. The most common clinical manifestation was urinary tract infection. Ultrasonography, urodynamic study and voiding cystourethrogram were used to delineate the cause and help to decide the appropriate treatment. In conclusion, early detection and prevention of deteriorated renal function are important for children with urinary bladder outlet obstruction.

Symptomatic hypomagnesemia in children.

Between January 1996 and June 1998, 24 children with symptomatic hypomagnesemia were enrolled for analysis of their symptomatology, causes, and treatment outcome. Hypocalcemia and hyperphosphatemia suggesting impaired parathyroid function were the most common electrolyte disorders. Hypokalemia was also frequently noted. The related symptoms including seizure, tetany, and weakness were common. Drug-induced renal magnesium wasting was the most common cause of symptomatic hypomagnesemia, and tended to occur in older children using aminoglycoside, furosemide, and amphotericin-B. The associated gastrointestinal causes might add a minor contribution to the development of hypomagnesemia. Analyses of PTH levels in 13 children suggested that inhibition of PTH synthesis or secretion was responsible for hypomagnesemic hypocalcemia in most patients. However, peripheral PTH resistance might also account for the mechanism in a few patients. In most patients, symptomatic hypomagnesemia was transient, and improved after magnesium provision. Only one child with congenital renal magnesium wasting and two with primary hypomagnesemia needed long-term magnesium treatment.

Correlation of quantitative renal cortical echogenicity with renal function in pediatric renal diseases.

Using quantitative echogenicity, the correlation between renal cortical echogenicity and renal function (serum creatinine) was evaluated in pediatric renal diseases. The kidney/liver echogenicity ratio (K/ L ratio) was measured by computerized amplitude histogram in 20 healthy children as well as in 45 children with renal diseases, including 12 glomerulonephritis with chronic renal failure (CRF), 9 anatomic-related CRF, 9 glomerulonephritis with acute renal failure (ARF), 5 nephrotoxic ARF, and 10 glomerulonephritis without renal failure. All children were above six years of age. Simultaneous serum creatinine was available during the procedure in all patients. The overall K/L ratio was 1.38 +/- 0.26 for CRF and 1.14 +/- 0.18 for ARF (p = 0.007), while the overall serum creatinine was 312 +/- 160 mumol/L (3.5 +/- 1.8 mg/dl) and 191 +/- 73 mumol/L (2.2 +/- 0.8 mg/dl), respectively (p = 0.013). K/L ratio was higher in CRF at a higher, or even at a comparable serum creatinine level, than in ARF. For patients with glomerulonephritis, K/L ratio was highest in those with CRF, next in those with ARF. Even in glomerulonephritis without renal failure, the K/L ratio was higher than in normal controls. There was a positive correlation between K/L ratio and serum creatinine concentration in glomerulonephritis with or without renal failure (r = 0.69, p < 0.001). These results suggest that the degree of increased renal echogenicity may reflect the severity of the renal disease. The K/L ratio measured by quantitative echogenicity may provide an additional simple noninvasive method to monitor the progression of glomerulonephritis.

Nephromegaly and elevated hepatocyte growth factor in children with biliary atresia.

Nephromegaly, a rarely mentioned but probably common situation, was studied in children with biliary atresia. We evaluated the length and the cross-sectional diameters of the kidney by ultrasound in 21 children with biliary atresia as well as in 50 healthy children. The ages ranged from 1 month to 10 years. Plasma hepatocyte growth factor (HGF) was measured in 18 children with biliary atresia and also in 18 age- and sex-matched normal controls. There was a significant nephromegaly (increase in the renal length and the kidney volume) in children with biliary atresia as compared with normal children (P < 0.001 by analysis of covariance). Plasma HGF levels were elevated in these patients (2.13 +/- 1.06 v 0.76 +/- 0.19 ng/mL in controls, P < 0.001) and had a positive correlation with the renal size after considering the effect of body height by multiple regression analysis (P = 0.0022 for renal length, and P < 0.001 for kidney volume). These results confirm the presence of large kidneys in biliary atresia and implicate the possible pathogenic role of HGF in such a condition. Nephromegaly in biliary atresia may provide a new in vivo model to study the mechanism of renal growth.