Clinical and laboratory findings in four patients with the non-progressive hepatic form of type IV glycogen storage disease.

The classic clinical presentation for type IV glycogen storage disease (branching enzyme deficiency, GSD IV) is hepatosplenomegaly with failure to thrive occurring in the first 18 months of life, followed by progressive liver failure and death by age 5 years. Although there have been two patients without apparent liver progression previously reported, no long-term follow-up clinical data have been available. We present here the clinical spectrum of the non-progressive liver form of GSD IV in four patients, and long-term follow-up of the oldest identified patients (ages 13 and 20 years). None has developed progressive liver cirrhosis, skeletal muscle, cardiac or neurological involvement, and none has been transplanted. Branching enzyme activity was also measured in cultured skin fibroblasts from patients with the classic liver progressive, the early neonatal fatal, and the non-progressive hepatic presentations of GSD IV. The residual branching enzyme activity in the patients without progression was not distinguishable from the other forms and could not be used to predict the clinical course. Our data indicate that GSD IV does not always necessitate hepatic transplantation and that caution should be used when counselling patients regarding the prognosis of GSD IV. Patients should be carefully monitored for evidence of progression before recommending liver transplantation.

Spontaneous pneumomediastinum in a patient with diabetic ketoacidosis: a potentially hidden complication.

A pediatric patient with diabetic ketoacidosis (DKA) was found to have a pneumomediastinum and a small pneumothorax. Because some of the signs and symptoms of pneumomediastinum may be confused with those of the patient's primary disease process, this complication may be present more frequently than has been previously described.

Diabetic nephropathy in a prepubertal diabetic female.

Diabetic nephropathy is an uncommon finding in the pediatric age group. Previous reports have demonstrated that persistent proteinuria does not occur during the first five years following the diagnosis of insulin dependent diabetes mellitus. We report a prepubertal female child with less than five years duration of diabetes who developed persistent proteinuria and histologic changes diagnostic of diabetic nephropathy. The earlier than expected diabetic nephropathy noted in our patient raises the question regarding the need for earlier surveillance for diabetic nephropathy in children with a family history of chronic diabetic complications.

Serum lipid concentrations in subjects with phenylketonuria and their families.

To determine if subjects with phenylketonuria receiving diets significantly lower in cholesterol and saturated fat had serum lipid concentrations different from those of their family members, we measured serum concentrations of total cholesterol, high-density lipoprotein cholesterol, and total triglycerides in the probands with phenylketonuria, their parents, and their siblings. Eleven adults (seven women and four men) and 16 children (eight girls and eight boys) were studied. Ten subjects (four girls and six boys) had phenylketonuria. Subjects with phenylketonuria consumed less cholesterol (0.02 vs 0.41 mmol/d) and fat (median, 21% vs 39.5% of total calories), and their diets had a higher ratio of polyunsaturated to saturated fatty acids (median, 2.0 vs 0.2) than did their siblings without phenylketonuria. The diet of the parents was similar to that of their offspring without phenylketonuria. No differences were noted between the subjects with phenylketonuria (consuming a diet lower in saturated fat and cholesterol) and their siblings without phenylketonuria in serum concentrations of total cholesterol (median, 3.34 vs 3.07 mmol/L); high-density lipoprotein cholesterol (median, 1.44 vs 1.37 mmol/L); low-density lipoprotein cholesterol (median, 1.44 vs 1.09 mmol/L); or triglycerides (median, 0.89 vs 0.54 mmol/L). We conclude that previously reported lipoprotein abnormalities noted between unrelated subjects with and without phenylketonuria may not be due to differences in dietary intake, but rather due to a (genetic) predisposition of the population with phenylketonuria toward lower serum lipid concentrations.

Insulin resistance and hyperinsulinemia induce hyperandrogenism in a young type B insulin-resistant female.

An adolescent female with type B insulin resistance and hyperandrogenemia is described. Evidence presented suggests that hyperinsulinemia leads to an increase in serum total and free testosterone. Support for this hypothesis is noted during an in vivo experiment in which large doses of regular insulin (305 U/kg-day) were infused iv, and multiple serum total testosterone measurements obtained. After 35 days of iv insulin therapy, the serum total testosterone values rose from 4.9 nmol/L (142 ng/dL) to 22.8 nmol/L (660 ng/dL), and the ovarian volume increased 2-fold. Basal (9.8 nmol/L; 282 ng/dL) and stimulated (16.8 nmol/L; 481 ng/dL) androstenedione measurements were elevated, and the dehydroepiandrosterone/androstenedione ratio was low, suggesting increased 3 beta-hydroxysteroid dehydrogenase activity. After resolution of the insulin-resistant state and the concomitant hyperinsulinemia, the serum total testosterone values returned to normal. This case illustrates that long term hyperinsulinemia leads to elevation of serum total testosterone.

Cholesterol screening management of Florida's pediatric population.

The current cholesterol screening and management of Florida's pediatric population is evaluated utilizing a questionnaire mailed to 1,534 pediatric health care providers. Twenty percent of the physicians responded. Of the respondents, 65% do not routinely screen for the presence of hypercholesterolemia. Only 28% of the respondents obtain serum total cholesterol measurements in accordance with the American Academy of Pediatrics Committee on Nutrition recommendations. The serum total cholesterol concentration prompting treatment was 240 mg/dL (6.2 mM). Dietary counseling alone, or in combination with exercise, was the initial treatment approach recommended by 98% of the responding physicians. Dietary education for the hypercholesterolemic patient was provided by both dieticians (46%) and physicians (42%). If the initial dietary intervention was unsuccessful, 48% of the physicians would begin medical therapy. The most commonly prescribed medication was a bile acid sequestrant (70%), with the majority (52%) referring their patient to a subspecialist for evaluation and care.

Florida newborn screening for galactosemia.

Galactosemia, an inborn error of metabolism characterized by the inability to transform galactose-1-phosphate into glucose-1-phosphate, occurs in 1:50,000 live births. If not diagnosed and treated within the newborn period, it can lead to severe morbidity and mortality within a few weeks of life. All children in Florida are screened for this disorder by a fluorescence assay system to measure galactose-1-phosphate uridyltransferase (GALT) activity in a dried blood spot. Genetic factors and external forces can affect the activity of the GALT enzyme and lead to confusing results. Parents of infants heterozygous for galactosemia should be offered the opportunity for carrier detection. If both are carriers, genetic counseling should be provided.