Abstract
Summary: Glycogenosis type IV is an autosomal recessive disease, exceptionally diagnosed at birth: only very few reports of the fatal perinatal neuromuscular form have been described. We report on two sibling male newborns who died at 10 and 4 weeks of age with clinical signs of a systemic storage disease. Prenatal history included polyhydramnios, reduced fetal movements and fetal hydrops, Caesarean section was performed at 36 weeks of gestational age because of fetal distress. At birth, both babies showed severe hypotonia, hyporeflexia and no spontaneous breathing activity. They never showed active movements, sucking and swallowing and were respirator-dependent until death. A muscle biopsy revealed, in both patients, the presence of PAS-positive and partially diastase-resistant cytoplasmic inclusions containing granular and filamentous amylopectin-like material. This suggested that the stored material consisted of abnormal glycogen. At autopsy, ultrastructural examination of cardiac and skeletal muscle, liver,kidney and brain showed PAS-positive diastase-resistant eosinophilic cytoplasmic inclusions. Determination of branching enzyme activity, in cultured fibroblasts from the second patient, showed markedly reduced enzyme activity, confirming diagnosis of glycogenosis type IV. Our patients showed the full spectrum of both prenatal signs (hydrops, polyhydramnios) and postnatal signs (hypotonia, hyporeflexia, absence of active movements, cardiomegaly), which have been reported previously. They suffered from a very severe form of glycogenosis type IV with clinical and histological involvement of many tissues and organs. Diagnosis was accomplished on the second baby and required several biochemical and histological studies, in order to rule out both neuromuscular disorders and the most common storage diseases with neonatal onset. In our experience, the correct interpretation of the histological findings was essential in the search for the diagnosis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Alegria A, Martins E, Dias M, Cunha A, Cardoso ML, Maire I (1999) Glycogen storage disease type IV presenting as hydrops fetalis. J Inherit Metab Dis 22: 330–332.
Andersen DH (1952) Studies ofglycogen disease with report ofa case in which the glycogen was abnormal. In: Najjar VA, ed. Carbohydrate Metabolism. Baltimore: Johns Hopkins Press, 28–42.
Bao Y, Kishnani P, Wu J-Y, Chen Y-T (1996) Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene. J Clin Invest 97: 941–948.
Barns RJ, Clague AE (1982) An improved procedure for diagnosis of Gaucher disease using cultured skin ?broblasts and the chromogenic substrate 2-hexadecanoylamino-4-nitrophenyl-b-D-glucopyranoside. Clin Chim Acta 120: 57–63.
Beutler E, Kuhl W, Trinidad F, Teplitz R, Nadler H (1971) Beta-glucosidase activity in ?broblasts from homozygotes and heterozygotes for Gaucher's disease. Am J Hum Genet 23: 62–66.
Brown BI (1985) Diagnosis ofglycogen storage disease. In Wapnir PA, ed. Congenital Metabolic Diseases: Diagnosis and Treatment. New York: Dekker, 227–250.
Brown BI, Brown DH (1966) Lack ofan a-1,4-glucan:a-1,4-glucan 6-glycosyl transferase in a case oftype IV glycogenosis. Proc Natl Acad Sci USA 56: 725–729.
Bruno C, Servidei S, Shanske S, et al (1993) Glycogen branching enzyme de?ciency in adult polyglucosan body disease. Ann Neurol 33: 88–93.
Bruno C, Di Rocco M, Doria-Lambda L, et al (1999) A novel missense mutation in the glycogen branching enzyme gene in a child with myopathy and hepatopathy. Neuromuscul Disord 9: 403–407.
Choy FY, Davidson RG (1980) Gaucher's disease. II. Studies on the kinetics of beta-glucosidase and the effects ofsodium taurocholate in normal and Gaucher tissues. Pediatr Res 14: 54–59.
Cox PM, Brueton LA, Murpy KW, et al (1999) Early-onset fetal hydrops and muscle degeneration in siblings due to a novel variant oftype IV glycogenosis. Am J Med Genet 86: 187–193.
Danon MJ, Oh SJ, DiMauro S, et al (1981) Lysosomal glycogen storage disease with normal acid maltase. Neurology 31: 51–57.
Gal AE, Brady RO, Barranger JA, Pentkey PG (1980) The diagnosis oftype A and type B Niemann-Pick disease and detection ofcarriers using leukocytes and a chromogenic analogue ofsphingomyelin. Clin Chim Acta 104: 129–132.
Greene HL, Brown BI, McClenathan DT, Agostini RM Jr, Taylor SR (1988) A new variant of type IV glycogenosis: de?ciency ofbranching enzyme activity without apparent progressive liver disease. Hepatology 8: 302–306.
Guerra AS, van Diggelen OP, Carneiro F, Tsou RM, Simoes S, Santos NT (1986) A juvenile variant ofglycogenosis IV (Andersen disease). Eur J Pediatr 145: 179–181.
Herrick MK, Twiss JL, Vladutiu GD, Glasscock GF, Horoupian DS (1994) Concomitant branching enzyme and phosphorylase de?ciencies. An unusual glycogenosis with extensive neuronal polyglucosan storage. J Neuropathol Exp Neurol 53: 239–246.
Hollak CE, van Weely S, van Oers MH, Aerts JM (1994) Marked elevation ofplasma chitrotriosidase activity. A novel hallmark ofGaucher disease. J Clin Invest 93: 1288–1292.
Illingworth B, Cori GT (1952) Structure ofglycogens and amylopectins. III. Normal and abnormal human glycogen. J Biol Chem 199: 653–660.
McConkie-Rossel A, Wilson C, Piccoli DA, et al (1996) Clinical and laboratory ?ndings in four patients with the non-progressive hepatic form of type IV glycogen storage disease. J Inherit Metab Dis 19: 51–58.
Moses SW, Parvari R (2002) The variable presentations ofglycogen storage disease type IV: a review ofclinical, enzymatic and molecular studies. Curr Mol Med 2: 177–188.
Nambu M, Kawabe K, Fukuda T, et al (2003). A neonatal form of glycogen storage disease type IV. Neurology 61: 392–394.
Ninomiya N, Matsuda I, Matsuoka T, Iwamasa T, Nonaka I (1984) Demonstration ofacid alpha-glucosidase in different types ofPompe disease by use ofan immunochemical method. J Neurol Sci 66: 129–139.
Nishino I, Fu J, Tanjl K, et al (2000) Primary LAMP-2 de?ciency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature 406: 906–910.
Schroder JM, May R, Shin YS, Sigmund M, Nase-Hüppmeier S (1993) Juvenile hereditary polyglucosan body disease with complete branching enzyme de?ciency (type IV glycogenosis). Acta Neuropathol 85: 419–430.
Stone DL, Sidransky E (1999) Hydrops fetalis: lysosomal storage disorders in extremis. Adv Pediatr 46: 409–440.
Tang TT, Segura AD, Chen YT, et al (1994) Neonatal hypotonia and cardiomyopathy secondary to type IV glycogenosis. Acta Neuropathol 87: 531–536.
Thon VJ, Khalil M, Cannon JF (1993) Isolation ofhuman glycogen branching enzyme cDNAs by screening complementation in yeast. J Biol Chem 268: 7509–7513.
Uro-Coste E, Lelong-Tissier M-C, Maire I, Ceuterick C, Chausseray F, Delisle M-B (1996) Glycog é nose type IV variante cong é nitale. Ann Pathol 16: 449–452.
van Noort G, Straks W, Van Diggelen OP, Hennekam RC (1993) A congenital variant of glycogenosis type IV. Pediatr Pathol 13: 685–698.
Zellweger H, Mueller S, Ionasescu V, Schochet SS, McCormick WF (1972) Glycogenosis IV: a new cause ofinf antile hypotonia. J Pediatr 80: 842–844.
Ziemssen F, Sindern E, Schroder JM, et al (2000) Novel missense mutations in the glycogen-branching enzyme gene in adult polyglucosan body disease. Ann Neurol 47: 536–540.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Giuffrè, B., Parini, R., Rizzuti, T. et al. Severe neonatal onset of glycogenosis type IV: Clinical and laboratory findings leading to diagnosis in two siblings. J Inherit Metab Dis 27, 609–620 (2004). https://doi.org/10.1023/B:BOLI.0000042980.45692.bb
Issue Date:
DOI: https://doi.org/10.1023/B:BOLI.0000042980.45692.bb