Glycogen storage disease type II differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Overview

Infantile onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, myopathy, dyspnea, feeding diffculties, absent reflex, macroglossia, hepatomegaly, heart failure, elevated CK, and cardiomegaly. Infantile onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, acute Werdnig-Hoffman disease (spinal muscular atrophy), hypothyroidism, endocardial fibroelastosis, myocarditis, congenital muscular dystrophy, mitochondrial/respiratory chain disorder, peroxisomal disorders. Late onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, muscle weakness, respiratory imapirement, difficulty in walking, hepatomegaly, elevated CK, and cardiomyopathy. Late onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, limb girdle muscle atrophy (LGMD), Becker muscular dystrophy (BMD), scapuloperonral syndromes, mitochondrial myopathies, myasthenia gravis, spinal muscular atrophy, polymyositis.

Differentiating Infantile Onset Glycogen Storage Disease Type II from other Diseases

• Infantile onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, myopathy, dyspnea, feeding diffculties, absent reflex, macroglossia, hepatomegaly, heart failure, elevated CK, and cardiomegaly. Infantile onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, acute Werdnig-Hoffman disease (spinal muscular atrophy), hypothyroidism, endocardial fibroelastosis, myocarditis, congenital muscular dystrophy, mitochondrial/respiratory chain disorder, peroxisomal disorders.
• Late onset glycogen storage disease type 2 (GSD type 2) must be differentiated from other diseases on the basis of characteristics including hypotonia, muscle weakness, respiratory imapirement, difficulty in walking, hepatomegaly, elevated CK, and cardiomyopathy. Late onset glycogen storage disease should be differentiated from glycogen storage disease type 3, glycogen storage disease type 4, limb girdle muscle atrophy (LGMD), Becker muscular dystrophy (BMD), scapuloperonral syndromes, mitochondrial myopathies, myasthenia gravis, spinal muscular atrophy, polymyositis.

Table Differentiating Infantile Onset Glycogen Storage Disease Type II from other Diseases

Diseases	History and Symptoms				Physical Examination				Laboratory Findings	Imaging findings
	Hypotonia	Myopathy	Dyspnea	Feeding difficulties	Absent reflex	Macroglossia	Hepatomegaly	Heart failure	Elevated CK	Cardiomegaly
Glycogen storage disease type II	+	+	+	+	+	+	+	+	+	+
Glycogen storage disease type III	-	+	-	-	-	-	+	-	+	+
Glycogen storage disease type IV	-	+	-	-	-	-	+	-	+	+
Acute Werdnig-Hoffmann disease (spinal muscular atrophy)	+	+	-	-	+	-	-	-	-	-
Hypothyroidism	+	-	-	-	-	+	-	-	-	-
Endocardial fibroelastosis	-	-	+	+	-	-	-	+	-	+
Myocarditis	-	-	-	-	-	-	-	-	-	+
Congenital muscular dystrophy	++	+	-	-	-	-	-	-	-	-
Mitochondrial/respiratory chain disorder	-	+	-	-	-	-	+	-	+	+
Peroxisomal disorders	+	-	-	-	-	-	+	-	-	-

Table Differentiating Late Onset Glycogen Storage Disease Type II from other Diseases

Diseases	History and Symptoms				Physical Examination	Laboratory Findings	Imaging findings
	Hypotonia	Muscle weakness	Respiratory impairement	Difficulty in walking	Hepatomegaly	Elevated CK	Cardiomyopathy
Glycogen storage disease type II	+	Progressive muscle weakness	+	+	+	+	+
Glycogen storage disease type III	+	Progressive muscle weakness	-	-	+	+	+/-
Glycogen storage disease type IV	+	Progressive muscle weakness	-	-	+	+	+/-
Limb girdle muscular atrophy (LMGD)	-	Progressive muscle weakness in pelvis, legs, and shoulders	-	-	-	-	-
Becker muscular dystrophy (BMD)	-	Progressive proximal muscle weakness	+	+	-	+	-
Scapuloperoneal syndromes	-	Progressive muscle weakness behind the knee and around the shoulder blades	-	-	+	+	+
Mitochondrial myopathies	+	Muscle weakness	-	-	+	+	+
Myasthenia gravis	-	Generalized muscle weakness	-	-	-	-	-
Spinal muscular atrophy	-	Asymmetrical muscle weakness, atrophy of voluntary muscles	-	-	-	-	-
Polymyositis	-	Unexplained muscle weakness	-	-	-	-	-