George Hug

Elevated serum 1,25 dihydroxyvitamin D concentrations in rickets of very low-birth-weight infants.

Elevated 1,25 dihydroxyvitamin D concentrations were found in five VLBW infants who developed rickets at two to three months postnatal age or term postconceptual age; 25 hydroxyvitamin D concentrations were low. Bone mineralization was found to be extremely low as measured by infant-adapted direct photon absorptiometry. After treatment with a formula supplemented with additional Ca and P, there was a rapid improvement in bone mineralization with a concomitant decrease of 1,25(OH)2D to normal adult values, whereas 250HD values increased and parathyroid hormone values decreased. In the VLBW infants studied, we suggest that rickets may be caused by Ca and P deficiency rather than by a deficiency of vitamin D metabolism.

Glucagon tolerance test in glycogen storage disease.

Summary 1. Glucagon injected intravenously in a patient with generalized glycogen storage disease produces a normal rise in blood sugar, even in a starving state. Such a blood sugar response excludes the possibility of von Gierkes disease and of Coris disease. 2. Glucagon injected intravenously in a patient with either von Gierkes disease or with Coris disease does not produce a normal rise in blood sugar provided the patient has been kept starving. 3. Glucagon injected intravenously in a patient with von Gierkes disease does not produce a rise in blood sugar even when done 2 hours after the patient has been given a substantial meal. 4. Glucagon injected intravenously in a patient with Coris disease does produce a normal rise in blood sugar provided the patient has been given a substantial meal two hours prior to testing. 5. It is important to starve the patient long enough (not less than 14 hours) prior to the second glucagon tolerance test. Thus, a sufficient degradation of the outer branches of the glycogen molecule in Coris disease is assured. Normal individuals react with a normal glucagon tolerance curve even after 48 hours of starvation. No other metabolic disorders are presently known which might interfere with this test. Equivocal results can be obtained in cases where the deficiency of glucose-6-phosphatase is only moderate. The more rare forms of glycogen storage disease (other than Types 1 and 3) can only be ruled out with the test.

Chronic lactic acidosis of infancy

A 6-month-old girl was followed until age 14 months because of recurrent acidosis and found to have chronically elevated serum and urinary concentrations of lactate, pyruvate, and alpha ketoglutarate. Abnormalities in the patient not described in previous patients with chronic lactic acidosis were anemia with spiculated erythrocytes, nuclear cataracts, and spongy degeneration of the brain. The biochemical findings suggest a deficiency of a factor necessary for the normal decarboxylation of pyruvate. Because of the biochemical similarities of chronic lactic acidosis to conditions of thiamine deficiency and altered thiamine metabolism, and because thamine concentrations in serum and red blood cells of other patients with chronic lactic acidosis have been normal, a defect in thiamine metabolism is postulated.

Type VI glycogenosis: Biochemical demonstration of liver phosphorylase deficiency

Abstract A boy with hepatomegaly had increased glycogen and low activity of liver phosphorylase. Muscle tissue was normal. Conversion of rabbit muscle phosphorylase b to phosphorylase a by his liver homogenate indicated its normal capacity for phosphorylase activation. The patients hepatic homogenate failed to develop phosphorylase activity under conditions that in control homogenates revealed the presence of endogenous phosphorylase through its activation. The failure was not corrected by the addition of phosphorylase kinase to the patients homogenate. The results indicate liver phosphorylase deficiency or type VI glycogenosis.

Lysosomal Diseases and Fibroblast Cultures: Biochemical and Electron Microscopic Observations

Most lysosomal diseases are fatal, often after a protracted downhill course that is painfully apparent to patient, parents and physician. This interim report relates our attempts to treat such patients; and to find ultrastructural and biochemical markers in fibroblast cultures for the study of pathophysiology and treatment of lysosomal disease.