In vivo evidence of brain galactitol accumulation in an infant with galactosemia and encephalopathy.

In a newborn infant with galactose-1-phosphate uridyltransferase deficiency and encephalopathy, brain magnetic resonance imaging revealed cytotoxic edema in white matter. Using in vivo proton magnetic resonance spectroscopy, we detected approximately 8 mmol galactitol per kilogram of brain tissue, an amount potentially relevant to the pathogenesis of brain edema.

Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase.

OBJECTIVES: The incidence and severity of growth retardation in children with type 1 Gaucher disease and the response to enzyme replacement therapy with alglucerase were studied. STUDY DESIGN: A retrospective analysis of growth in 99 children and adolescents with type 1 Gaucher disease before treatment, and in 54 of those subjects during treatment, was done. Growth was compared with gender, age, and dosage of replacement enzyme. RESULTS: Linear growth was normal in the first 1 to 2 years of life and then decelerated. Height was at or below the 5th percentile in 50% of all subjects immediately before treatment. The mean z score was -1.49 (95% confidence interval, -1.83 to -1.16), corresponding to the 6.8th percentile for height. Seventy-two percent were below the 50th percentile and 50% were at or below the 5th percentile for mid-parental height (p <0.001). One and one-half years after treatment was started, the estimated mean z score for all subjects was -1.01, which corresponds to the 16th percentile for height. Normal growth was achieved within 4 to 30 months in eight of nine subjects who were at or below the 5th percentile. It occurred only in those receiving higher doses (60 to 120 U/kg per 4-week period) of alglucerase. There was a significant association between z scores for height before treatment and liver enlargement (r= 0.57; p < 0.01). CONCLUSIONS: Half of the subjects who manifest type 1 Gaucher disease in childhood have growth retardation. Treatment with adequate amounts of modified enzyme replacement was effective in normalizing linear growth.

Painful keratoderma and photophobia: hallmarks of tyrosinemia type II.

Tyrosinemia type II (Richner-Hanhart syndrome), which is caused by a deficiency of hepatic tyrosine aminotransferase, results in elevated plasma and urinary tyrosine concentrations. We describe a young boy who was seen at 6 months of age with red eyes, photophobia, and eye pain that were not suspected to be caused by tyrosinemia II until painful plantar keratoderma developed at 2 1/2 years of age. Treatment with a diet low in tyrosine and phenylalanine reversed the manifestations of the disease.

Intellectual outcome in children with maple syrup urine disease.

We report a controlled study of intellectual outcome in 16 children with maple syrup urine disease (MSUD) that compares the outcome of MSUD diagnosed after symptoms became apparent with that of MSUD diagnosed prospectively and in unaffected siblings and parents. The mean IQ (+/- SD) score in the children with classic MSUD was 78 +/- 24; however, there were two discrete groups: one with normal IQ (greater than 84) whose MSUD had been diagnosed at a mean age of 3.5 days and a second group, with IQ below normal, whose MSUD was diagnosed at a mean of 10 days of age. Affected children treated presymptomatically had higher IQ scores than their affected siblings treated when their disease was symptomatic. Multiple regression analysis indicated that the important influences on IQ were age at the time of diagnosis and long-term metabolic control; control at the time of testing also might have affected performance. The mean score of unaffected siblings was 92 +/- 5 and the mean parental IQ was 83 +/- 9. The mean IQ scores of children with variant MSUD, 97 +/- 4, was similar to that of their parents, 103 +/- 6. This study was not longitudinal and thus could not identify subtle developmental learning problems. We conclude that early and meticulous treatment of MSUD can result in intellectually normal children.

25-hydroxyvitamin D3 (calcifediol) therapy of juvenile renal osteodystrophy: beneficial effect on linear growth velocity.

A prospective study of renal osteodystrophy in moderate renal insufficiency was undertaken to assess the effects of 25(OH)D3 (Calcifediol) on healing of bone lesions and improvement of linear growth. One year after entering the study, the mean group growth velocity increased into the normal range and remained there in the next two therapy years. A significant correlation existed between pretherapy and one-year therapy values of growth velocity and serum 25(OH)D3 concentration. Qualitative bone histology obtained by transilial bone biopsy was also evaluated during the course of study. Catch-up growth was not seen, but potential for such growth may exist in later years in our patients.

Long-term treatment of familial hypophosphatemic rickets with oral phosphate and 1 alpha-hydroxyvitamin D3.

Combined treatment with oral phosphate and 1 alpha (OH)D3 was carried out in nine children with familial hypophosphatemic rickets. All nine had positive responses over a four- to six-year period as judged by healing of rickets, change in growth rate, decrease in alkaline phosphatase activity, and symptomatic improvement. In two patients therapy was stopped for a short time because of hypercalcemia. In one patient in whom therapy was effective there was a significant reduction in creatinine clearance which necessitated cessation of treatment. The results of this study suggest that combined treatment with 1 alpha(OH)D3 and oral phosphate is an effective form of therapy for this condition, but that the balancing of these two modalities of therapy in each patient is essential if hypercalcemia and hypercalciuria, on the one hand, and secondary hyperparathyroidism, on the other, are to be avoided. A simple means of balancing these therapeutic modalities is suggested.

Early diagnosis of juvenile renal osteodystrophy.

Renal osteodystrophy has assumed growing importance as a major and frequently disabling complication of chronic renal failure in children since the advent of successful hemodialysis and renal transplantation programs. The frequency and severity of renal osteodystrophy appears greatest in younger children with congenital diseases of the kidney and urinary tract, who experience long intervals of chronic renal failure prior to reaching end-stage. Twenty-nine children with varying degrees of chronic renal failure were studied to learn: (1) how early renal osteodystrophy can be diagnosed; and (2) how the various clinical, biochemical, and hormonal abnormalities correlate with abnormal bone histomorphometry as determined from percutaneous transilial bone biopsies. Results showed: (1) marked-to-moderate reductions in GFR (mean = 35 ml/minute/1.73 m2; range 11 to 65 ml/minute/1.73 m2); (2) elevations of serum PTH concentrations in all patients with a GFR < 45 ml/minute/1.73 m2; (3) abnormal bone histomorphometry in all patients with elevated PTH concentrations; (4) "early" renal osteodystrophy (elevated PTH concentrations and abnormal bone histomorphometry but normal serum chemistry values and radiographs) in one quarter of the patients; (5) poor correlations of serum chemistry values and radiographs with bone histomorphometry; and (6) a wide range of histologic abnormalities including predominant osteomalacia (n = 7), predominant hyperparathyroidism (n = 6), or a mixed picture (n = 11).