METHODS: Eighty consecutive muscle biopsies in the Department of Pathology, National University of Singapore, in the period 1978-2000, in which a clinical diagnosis of floppy or hypotonic infant was made, were reviewed.
RESULTS: The commonest cause of severe hypotonia in infancy was spinal muscular atrophy, which accounted for 33% of cases followed by congenital muscular dystrophy (13%). Eight cases (10%) of infantile type II glycogenosis (Pompe's disease) were encountered. There were seven cases of congenital myopathy, of which four were centronuclear myopathy, and one each of central core myopathy, nemaline myopathy and congenital fibre type disproportion. One case of centronuclear myopathy was associated with type I fibre smallness. Type II atrophy, which is generally considered a non-specific change, was encountered in five cases. Of interest is the relatively large number of muscle biopsies (29%) in which no significant pathological features were encountered at the light microscopic, histochemical as well as ultra-structural level.
CONCLUSIONS: The study has revealed a great variety of pathology affecting the muscle of children presenting as floppy infants or with hypotonia. The muscle diseases included spinal muscular atrophy, congenital muscular dystrophies, congenital myopathies and metabolic myopathies. However, 23 (29%) cases showed no significant pathology. For this group of floppy and hypotonic infants further studies are needed.
METHODS: Seventeen patients diagnosed with IOPD between 2000 and 2020 were included in this retrospective cohort study. Clinical and biochemical data were collated and analyzed using descriptive statistics. GAA enzyme levels were performed on dried blood spots. Molecular analysis of the GAA gene was performed by polymerase chain reaction and Sanger sequencing. Structural modelling was used to predict the effect of the novel mutations on enzyme structure.
RESULTS: Our cohort had a median age of presentation of 3 months and median age of diagnosis of 6 months. Presenting features were hypertrophic cardiomyopathy (100%), respiratory insufficiency (94%), hypotonia (88%), failure to thrive (82%), feeding difficulties (76%), and hepatomegaly (76%). Fourteen different mutations in the GAA gene were identified, with three novel mutations, c.1552-14_1552-1del, exons 2-3 deletion and exons 6-10 deletion. The most common mutation identified was c.1935C > A p.(D645E), with an allele frequency of 33%. Sixteen patients received ERT at the median age of 7 months. Overall survival was 29%. Mean age of death was 17.5 months. Our longest surviving patient has atypical IOPD and is currently 20 years old.
CONCLUSIONS: This is the first study to analyze the genotype and phenotype of Malaysian IOPD patients, and has identified the c.1935C > A p.(D645E) as the most common mutation. The three novel mutations reported in this study expands the mutation spectrum for IOPD. Our low survival rate underscores the importance of early diagnosis and treatment in achieving better treatment outcomes.
CASE: Here we describe three infants with TNMG. Two of them developed symptoms of TNMG within 24 hours of life, but one developed symptoms at 43 hours of life. One of the patients had an atypical form of TNMG with contracture and hypotonia. The other two infants survived a typical form of TNMG with hypotonia and poor sucking. All cases resolved spontaneously by one to two weeks of life with conservative management.
CONCLUSIONS: Infants born to mothers with myasthenia gravis need to be monitored closely for symptoms of TNMG for the first 48 to 72 hours of life. However, the majority of infants with TNMG traverse a benign course and resolve spontaneously with expectant care.