Acta Padiatr Scand 67: 201-207, 1978
STUDIES ON A PATIENT WITH IN VIVOEVIDENCE OF TYPE I GLYCOGENOSIS AND NORMAL ENZYME ACTIVITIES IN VITRO R. A. CHALMERS,' BRENDA E. RYMAN2 and R. W. E. W A T T S From the 'Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Warford Road, Harrow, and 'Department of Biochemistry, Charing Cross Hospital Medical School, Hammersmith, London, U . K .
ABSTRACT. Chalmers, R. A., Ryman, B. E., and Watts, R. W. E. (Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Watford Road, Harrow, HA1 3UJ, and Department of Biochemistry, Charing Cross Hospital Medical School, Hammersmith, London, U.K.). Studies on a patient with in vivo evidence of type I glycogenosis and normal enzyme activities in vitro. Acta Paediatr Scand, 67: 201, 1978.-Biochemical and clinical studies on a patient with hepatic glycogen storage disease are reported. The patient showed many of the clinical and biochemical features of type I glycogenosis (glucose-6-phosphatase deficiency), but had normal activities of the following enzymes in liver tissue: glucose-6-phosphatase (EC3.1.3.9); amylo-l,6-glucosidase (EC3.2.1.33); glycogen phosphorylase (EC2.4.1.1); fructose-1,ddiphosphatase (EC3.1.3.11). The urinary excretion of 2-oxoglutaric acid was greatly increased in this patient and in a case of enzymologically proven type I glycogenosis. Abnormal 2-oxoglutaric aciduria has not been previously reported in the glycogen storage diseases. The results are discussed in relation to the possible nature of the underlying biochemical defect in patients of this type. KEY WORDS: Glycogen storage diseases; glycogenosistype I variant; enzymes; 2-oxoglutaric aciduria
The known pathways of glycogen synthesis and degradation, and the position of the enzyme deficiencies which are associated with the different types of glycogenosis (glycogen storage diseases) are shown in Fig. 1. These diseases are rare and have a combined incidence of between about 1 in 40000 and 1 in 70000 (13, 17). Type I glycogenosis [congenital deficiency of glucose-6-phosphatase (EC3.1.3.9)] is one of the more common types, but there are occasional cases of excessive glycogen storage associated with the clinical and other features of type I glycogenosis in whom the enzyme defect is not demonstrable in vitro (4, 25). This paper reports the results of detailed studies in such a case.
THE PATIENT The patient was the first child of healthy unrelated parents, and had a healthy younger sister. Gestation and delivery were normal (birth weight 2.2 kg), and he had presented at 11 weeks with an irreducible right inguinal hernia and an enlarged liver (lower edge palpable 8 cm below the right costal margin; blood urea 9.3 mmol/l, plasma bicarbonate 2.5 mmol/l, blood glucose 2.8 mmol/l). He had been seen again at 5 months because of an attack of diarrhoea which lasted 5 weeks. Growth retardation, liver enlargement into the right iliac fossa and a poor response to oral glucose with a flat glucose tolerance curve were recorded at one year. The enlarged liver accumulated radioactive colloid (metastable technetium) poorly and this was associated with increased uptake by the normal size spleen. Intravenous urography showed normal size kidneys. A liver biopsy at 14 months showed abnormal storage of glycogen but no enzymological evidence to support a diagnosis of either Types I, I1 or 111 glycogenosis (see Results). Random specimens of urine consistently conActa Prediatr Srand 67
202
R . A . Chalmers et al. ~~-
r .I--, Glucose
I
ilysoS3d;nalr
Glucose d -hosp(ate
4 ’
-
6-
1
GLYCOGEN
*
+Glucose 1phosphate
~, 2*
STUDIES ON A PATIENT WITH IN VIVOEVIDENCE OF TYPE I GLYCOGENOSIS AND NORMAL ENZYME ACTIVITIES IN VITRO R. A. CHALMERS,' BRENDA E. RYMAN2 and R. W. E. W A T T S From the 'Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Warford Road, Harrow, and 'Department of Biochemistry, Charing Cross Hospital Medical School, Hammersmith, London, U . K .
ABSTRACT. Chalmers, R. A., Ryman, B. E., and Watts, R. W. E. (Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Watford Road, Harrow, HA1 3UJ, and Department of Biochemistry, Charing Cross Hospital Medical School, Hammersmith, London, U.K.). Studies on a patient with in vivo evidence of type I glycogenosis and normal enzyme activities in vitro. Acta Paediatr Scand, 67: 201, 1978.-Biochemical and clinical studies on a patient with hepatic glycogen storage disease are reported. The patient showed many of the clinical and biochemical features of type I glycogenosis (glucose-6-phosphatase deficiency), but had normal activities of the following enzymes in liver tissue: glucose-6-phosphatase (EC3.1.3.9); amylo-l,6-glucosidase (EC3.2.1.33); glycogen phosphorylase (EC2.4.1.1); fructose-1,ddiphosphatase (EC3.1.3.11). The urinary excretion of 2-oxoglutaric acid was greatly increased in this patient and in a case of enzymologically proven type I glycogenosis. Abnormal 2-oxoglutaric aciduria has not been previously reported in the glycogen storage diseases. The results are discussed in relation to the possible nature of the underlying biochemical defect in patients of this type. KEY WORDS: Glycogen storage diseases; glycogenosistype I variant; enzymes; 2-oxoglutaric aciduria
The known pathways of glycogen synthesis and degradation, and the position of the enzyme deficiencies which are associated with the different types of glycogenosis (glycogen storage diseases) are shown in Fig. 1. These diseases are rare and have a combined incidence of between about 1 in 40000 and 1 in 70000 (13, 17). Type I glycogenosis [congenital deficiency of glucose-6-phosphatase (EC3.1.3.9)] is one of the more common types, but there are occasional cases of excessive glycogen storage associated with the clinical and other features of type I glycogenosis in whom the enzyme defect is not demonstrable in vitro (4, 25). This paper reports the results of detailed studies in such a case.
THE PATIENT The patient was the first child of healthy unrelated parents, and had a healthy younger sister. Gestation and delivery were normal (birth weight 2.2 kg), and he had presented at 11 weeks with an irreducible right inguinal hernia and an enlarged liver (lower edge palpable 8 cm below the right costal margin; blood urea 9.3 mmol/l, plasma bicarbonate 2.5 mmol/l, blood glucose 2.8 mmol/l). He had been seen again at 5 months because of an attack of diarrhoea which lasted 5 weeks. Growth retardation, liver enlargement into the right iliac fossa and a poor response to oral glucose with a flat glucose tolerance curve were recorded at one year. The enlarged liver accumulated radioactive colloid (metastable technetium) poorly and this was associated with increased uptake by the normal size spleen. Intravenous urography showed normal size kidneys. A liver biopsy at 14 months showed abnormal storage of glycogen but no enzymological evidence to support a diagnosis of either Types I, I1 or 111 glycogenosis (see Results). Random specimens of urine consistently conActa Prediatr Srand 67
202
R . A . Chalmers et al. ~~-
r .I--, Glucose
I
ilysoS3d;nalr
Glucose d -hosp(ate
4 ’
-
6-
1
GLYCOGEN
*
+Glucose 1phosphate
~, 2*
