Infantile Glycogen Storage Disease Type Research Articles

Clinical features analysis of non-classic infantile glycogen storage disease type II

Objective To summarize the clinical features of non-classic infantile glycogen storage disease type Ⅱ for early diagnosis. Methods The clinical data including the clinical manifestations and investigation of the 3 non-classic infantile glycogen storage disease type Ⅱ were retrospectively reviewed from Jun. to Jul. 2011. All the 3 cases were diagnosed by measuring acid α-glucosidase(GAA) activity in blood sample. Results All the 3 patients presented development delay, limb muscle weakness without hepatomegaly. Two cases of them presented weakness of respiratory muscle. The serum creatine kinase, aspartate aminotransferase and alanine aminotransferase were high in all the 3 patients. Electromyography studies indicated that one of the patients with susceptible myopathy, one patient with neurogenic damage and one patient with mixed damage of the neuromascular. Echographic evidence of hypertrophic cardiomyopathy was detected in 2 patients. GAA activity of the 3 patients in blood sample had diagnostic value. Conclusions Non-classic infantile glycogen storage disease type Ⅱis easy to be missed due to its non-significant clinical manifestations. The results suggested that GAA activity in blood sample should be screened for the patients with motor development delay, decreased muscle weakness/exercise tolerance and increased of serum creatine kinase. Key words: Infantile glycogen storage disease type Ⅱ; Acid alpha-glucosidase; Creatine kinase

Inconsistent reporting about dosing, dosing regimen, and immunomodulation therapy in Pompe disease

To the Editor: In 2001, Genetics in Medicine published an article titled “Recombinant Human Acid α-Glucosidase Enzyme Therapy for Infantile Glycogen Storage Disease Type II: Results of a Phase I/II Clinical Trial.”1 One of the three patients in that publication (“patient 1”) was recently presented anew in a case report by Banugaria et al.2

Response to Reuser

To the Editor: We read with interest the letter by Dr Reuser titled “Inconsistent Reporting About Dosing, Dosing Regimen, and Immunomodulation Therapy in Pompe Disease.”1 In our 2001 article, “Recombinant Human Acid α-Glucosidase Enzyme Therapy for Infantile Glycogen Storage Disease Type II: Results of a Phase I/II Clinical Trial,”2 we had reported the initial use of recombinant human acid α-glucosidase (rhGAA) in three infantile patients with Pompe disease.

Intraventricular Enzyme Replacement Improves Disease Phenotypes in a Mouse Model of Late Infantile Neuronal Ceroid Lipofuscinosis

Late infantile neuronal ceroid lipofuscinosis (LINCL) is an autosomal recessive neurodegenerative disease caused by mutations in CLN2, which encodes the lysosomal protease tripeptidyl peptidase 1 (TPP1). LINCL is characterized clinically by progressive motor and cognitive decline, and premature death. Enzyme-replacement therapy (ERT) is currently available for lysosomal storage diseases affecting peripheral tissues, but has not been used in patients with central nervous system (CNS) involvement. Enzyme delivery through the cerebrospinal fluid is a potential alternative route to the CNS, but has not been studied for LINCL. In this study, we identified relevant neuropathological and behavioral hallmarks of disease in a mouse model of LINCL and correlated those findings with tissues from LINCL patients. Subsequently, we tested if intraventricular delivery of TPP1 to the LINCL mouse was efficacious. We found that infusion of recombinant human TPP1 through an intraventricular cannula led to enzyme distribution in several regions of the brain of treated mice. In vitro activity assays confirm increased TPP1 activity throughout the rostral-caudal extent of the brain. Importantly, treated mice showed attenuated neuropathology, and decreased resting tremor relative to vehicle-treated mice. This data demonstrates that intraventricular enzyme delivery to the CNS is feasible and may be of therapeutic value.

L-alanine supplementation in late infantile glycogen storage disease type II

We report a male with late infantile glycogen storage disease type II (Pompe’s disease) who presented at 12 months of age with muscular hypotonia and developmental delay. Oral supplementation with l-alanine has been administered for 5 years. Progression of skeletal myopathy was slow, and cardiomyopathy resolved almost completely. l-alanine may be a valuable supplement for infants with glycogen storage disease type II.

Recombinant human acid α-glucosidase enzyme therapy for infantile glycogen storage disease type II: Results of a phase I/II clinical trial

Purpose: Infantile glycogen storage disease type II (GSD-II) is a fatal genetic muscle disorder caused by deficiency of acid α-glucosidase (GAA). The purpose of this study was to investigate the safety and efficacy of recombinant human GAA (rhGAA) enzyme therapy for this fatal disorder.Methods: The study was designed as a phase I/II, open-label, single-dose study of rhGAA infused intravenously twice weekly in three infants with infantile GSD-II. rhGAA used in this study was purified from genetically engineered Chinese hamster ovary (CHO) cells overproducing GAA. Adverse effects and efficacy of rhGAA upon cardiac, pulmonary, neurologic, and motor functions were evaluated during 1 year of the trial period. The primary end point assessed was heart failure–free survival at 1 year of age. This was based on historical control data that virtually all patients died of cardiac failure by 1 year of age.Results: The results of more than 250 infusions showed that rhGAA was generally well tolerated. Steady decreases in heart size and maintenance of normal cardiac function for more than 1 year were observed in all three infants. These infants have well passed the critical age of 1 year (currently 16, 18, and 22 months old) and continue to have normal cardiac function. Improvements of skeletal muscle functions were also noted; one patient showed marked improvement and currently has normal muscle tone and strength as well as normal neurologic and Denver developmental evaluations. Muscle biopsies confirmed that dramatic reductions in glycogen accumulation had occurred after rhGAA treatment in this patient.Conclusions: This phase I/II first study of recombinant human GAA derived from CHO cells showed that rhGAA is capable of improving cardiac and skeletal muscle functions in infantile GSD-II patients. Further study will be needed to assess the overall potential of this therapy.

Recombinant human acid ??-glucosidase enzyme therapy for infantile glycogen storage disease type II: Results of a phase I/II clinical trial

Recombinant human acid ??-glucosidase enzyme therapy for infantile glycogen storage disease type II: Results of a phase I/II clinical trial

Identification of a de Novo Point Mutation Resulting in Infantile Form of Pompe′s Disease

One patient in a nonconsanguineous Taiwanese family with infantile glycogen storage disease type II (Pompe′s) disease was found to have a de novo mutation of C1933 to G transition in exon 14 of the human lysosomal α -D-glucosidase gene. Patient was homozygous and both parents were heterozygous for the mutant allele. The mutation caused an Asp to His substitution at amino acid position 645. The mutation was introduced in wild type lysosomal α -D-glucosidase cDNA and the mutant construct was expressed in vivo. The Glu to His substitution was proven to cause significant loss of enzyme activity. In homozygous form it leads to the severe infantile phenotype of Pompe′s disease.