J. Inher. Metab. Dis. 15 (1992) 933-934 © SSIEM and KluwerAcademicPublishers. Printed in the Netherlands
CASE REPORT Aspartyiglycosaminuria presenting with hepatosplenomegaly in early infancy J. C. Haworth, L. E. Seargeant and L. A. Dilling Aspartylglycosaminuria (AGU) (McKusick 208400) is a rare recessively inherited inborn error of glycoprotein degradation caused by deficiency of the lysosomal enzyme aspartylglucosaminidase (L-aspartamido-fi-N-acetylglucosamineamidohydrolase, EC 3.5.1.26) which cleaves the linkages between N-acetylglucosamine and asparagine found in glycopeptides. Accumulation of aspartytglucosamine in body fluids and tissues results in psychomotor retardation, short stature, coarsening of the facies, connective-tissue lesions and skeletal abnormalities beginning between 2 and 6 years of age. Over 100 cases have been reported among the Finnish population but very few from other countries (Beaudet and Thomas 1989). We report a patient who presented in early infancy with enlargement of the liver and spleen as the sole clinical manifestation of AGU. The patient, a girl, is the second child of non-consanguineous parents who are of mixed Danish, French, German, Russian and native Canadian Indian descent. The patient was found to have enlargement of the liver and spleen at 3 weeks of age. At 6 months she seemed to be growing and developing normally (weight, length and head circumference at 75th centile for age). She was normal in appearance. Her abdomen was prominent and the liver edge was palpable 4 cm below the right costal margin; the spleen was greatly enlarged to 6-8 cm below the left costal margin. An eye examination was normal. Serum levels of glucose, sodium, potassium, urea, creatinine, calcium, phosphorus, transaminases and amino acids were normal. She had a mild hypochromic microcytic anaemia (haemoglobin 95 g/L) and mild neutropenia and thrombocytopenia, presumably due to hypersplenism. The urine contained no excess of ketones, reducing substances, mucopolysaccharides or amino acids, but a pronounced peak of 2-hydroxyglutaric acid was found by gas chromatography-mass spectrometry on two occasions. On a third occasion, at 10 months of age, this metabolite was not found. Abdominal ultrasound showed multiple areas of increased echoic density in both kidneys. Although no vacuole-containing cells were found in the bone marrow, a few vacuoles were reported in peripheral lymphocytes at 14 months of age. Radiographs of the skeleton were normal, apart from some apparent widening of the cranial sutures. Activities of hexosaminidase in serum and of fl-galactosidase and fl-glucosidase in leukocytes were normal. Analysis of urine showed increased oligosaccharides. Aspartylglucosamine, measured on a
Department of Pediatrics and Child Health, Children's Hospital, 840 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1S1; Department of Biochemistryand Molecular Biology, University of Manitoba 933
934
Case Reports
Beckman amino acid analyser, was 700 #mol/mmoi creatinine. Aspartylglucosaminidase activity measured in white blood cells (Aula et al t984) was undetectable (controls: n = 6, range 135-173 nmol/min per g protein). The majority of reported cases of AGU have been physically and developmentally normal for the first few years of life, although recurrent infections and diarrhoea during the first year or so were reported in some. Hepatomegaly has been described infrequently and in a few cases it has been transient (Beaudet and Thomas 1989). Splenomegaly has, to our knowledge, been described in only one patient (Isenberg and Sharp 1975). It was the hepatosplenomegaly that brought the patient to our attention and led to the diagnosis of AGU at an early age. At present she shows none of the features of the typical phenotype, but presumably will begin to show developmental regression and coarsening of the facial features in the years ahead. The frequency of AGU in eastern and northern Finland has been estimated as 1 : 4000 to 1 : 7000. In other countries only isolated cases have been reported. We know of only three other patients in Canada. AGU should be considered in infants with unexplained hepatosplenomegaly. Analysis of the urine for oligosaccharides can be done in most laboratories where inherited metabolic diseases are investigated. REFERENCES
Aula P, Rapola J, yon Koskult H, Ammala P (1984) Prenatal diagnosis and tbtal pathology of aspartylglucosaminuria. Am d Med Genet 19: 359-361. Beaudet AL, Thomas GH (t989) Disorders of glycoprotein degradation: mannosidosis, fucosidosis, sialidosis, and aspartylglucosaminuria. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease, 6th edn. New York: McGraw-Hill, 1603-1621. Isenberg JN, Sharp HL (1975) Aspartylglucosaminuria: psychomotor retardation masquerading as a mucopolysaccharidosis, d Pediatr 86: 713-717.
J. Inher. Merab. Dis. 15 (1992)
CASE REPORT Aspartyiglycosaminuria presenting with hepatosplenomegaly in early infancy J. C. Haworth, L. E. Seargeant and L. A. Dilling Aspartylglycosaminuria (AGU) (McKusick 208400) is a rare recessively inherited inborn error of glycoprotein degradation caused by deficiency of the lysosomal enzyme aspartylglucosaminidase (L-aspartamido-fi-N-acetylglucosamineamidohydrolase, EC 3.5.1.26) which cleaves the linkages between N-acetylglucosamine and asparagine found in glycopeptides. Accumulation of aspartytglucosamine in body fluids and tissues results in psychomotor retardation, short stature, coarsening of the facies, connective-tissue lesions and skeletal abnormalities beginning between 2 and 6 years of age. Over 100 cases have been reported among the Finnish population but very few from other countries (Beaudet and Thomas 1989). We report a patient who presented in early infancy with enlargement of the liver and spleen as the sole clinical manifestation of AGU. The patient, a girl, is the second child of non-consanguineous parents who are of mixed Danish, French, German, Russian and native Canadian Indian descent. The patient was found to have enlargement of the liver and spleen at 3 weeks of age. At 6 months she seemed to be growing and developing normally (weight, length and head circumference at 75th centile for age). She was normal in appearance. Her abdomen was prominent and the liver edge was palpable 4 cm below the right costal margin; the spleen was greatly enlarged to 6-8 cm below the left costal margin. An eye examination was normal. Serum levels of glucose, sodium, potassium, urea, creatinine, calcium, phosphorus, transaminases and amino acids were normal. She had a mild hypochromic microcytic anaemia (haemoglobin 95 g/L) and mild neutropenia and thrombocytopenia, presumably due to hypersplenism. The urine contained no excess of ketones, reducing substances, mucopolysaccharides or amino acids, but a pronounced peak of 2-hydroxyglutaric acid was found by gas chromatography-mass spectrometry on two occasions. On a third occasion, at 10 months of age, this metabolite was not found. Abdominal ultrasound showed multiple areas of increased echoic density in both kidneys. Although no vacuole-containing cells were found in the bone marrow, a few vacuoles were reported in peripheral lymphocytes at 14 months of age. Radiographs of the skeleton were normal, apart from some apparent widening of the cranial sutures. Activities of hexosaminidase in serum and of fl-galactosidase and fl-glucosidase in leukocytes were normal. Analysis of urine showed increased oligosaccharides. Aspartylglucosamine, measured on a
Department of Pediatrics and Child Health, Children's Hospital, 840 Sherbrook Street, Winnipeg, Manitoba, Canada R3A 1S1; Department of Biochemistryand Molecular Biology, University of Manitoba 933
934
Case Reports
Beckman amino acid analyser, was 700 #mol/mmoi creatinine. Aspartylglucosaminidase activity measured in white blood cells (Aula et al t984) was undetectable (controls: n = 6, range 135-173 nmol/min per g protein). The majority of reported cases of AGU have been physically and developmentally normal for the first few years of life, although recurrent infections and diarrhoea during the first year or so were reported in some. Hepatomegaly has been described infrequently and in a few cases it has been transient (Beaudet and Thomas 1989). Splenomegaly has, to our knowledge, been described in only one patient (Isenberg and Sharp 1975). It was the hepatosplenomegaly that brought the patient to our attention and led to the diagnosis of AGU at an early age. At present she shows none of the features of the typical phenotype, but presumably will begin to show developmental regression and coarsening of the facial features in the years ahead. The frequency of AGU in eastern and northern Finland has been estimated as 1 : 4000 to 1 : 7000. In other countries only isolated cases have been reported. We know of only three other patients in Canada. AGU should be considered in infants with unexplained hepatosplenomegaly. Analysis of the urine for oligosaccharides can be done in most laboratories where inherited metabolic diseases are investigated. REFERENCES
Aula P, Rapola J, yon Koskult H, Ammala P (1984) Prenatal diagnosis and tbtal pathology of aspartylglucosaminuria. Am d Med Genet 19: 359-361. Beaudet AL, Thomas GH (t989) Disorders of glycoprotein degradation: mannosidosis, fucosidosis, sialidosis, and aspartylglucosaminuria. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease, 6th edn. New York: McGraw-Hill, 1603-1621. Isenberg JN, Sharp HL (1975) Aspartylglucosaminuria: psychomotor retardation masquerading as a mucopolysaccharidosis, d Pediatr 86: 713-717.
J. Inher. Merab. Dis. 15 (1992)
