ABSTRACT
Objective: To study the etiology of neuroregression in children having deficiency of the lysosomal enzymes. Design: Review of medical records. Setting: Specialized Genetic Center. Participants: 432 children aged 3 mo-18 y having regression in a learned skill, selected from 1453 patients referred for diagnostic workup of various Lysosomal storage disorders (LSDs). Methods: Plasma chitotriosidase, quantitative and qualitative glycosaminoglycans, and mucolipidosis-II/II screening followed by confirmatory enzyme study using specific substrate was carried out; Niemann-Pick disease Type-C was studied by fillipin stain method on skin fibroblasts. Results: Total 309 children (71.5%) were diagnosed with different lysosomal storage disorders as the underlying cause of neuroregression. Plasma chitotriosidase was raised in 82 of 135; 64 (78%) of these had various LSDs. 69 out of 90 cases showed high excretion of glycoaminoglycans, and 67 (97.1%) of these were confirmed to have enzyme deficiency for various mucoplysaccharide disorders. While 3/90 children with positive I-cell screening had confirmed mucolipidosis-II/III disease. Among all, glycolipid storage disorders were the most common (50.2%) followed by mucopolysaccharidosis (MPS) (21.7%) and sulphatide degradation defect (17.5%). Neuronal ceroid lipofucinosis-1 & 2 (7.4%), mucolipidosis-II/III (1%), Sialic acid storage disorder (1%), Niemann-Pick disease type-C (1%) and Fucosidosis (0.3%) were observed with less frequency. Most common phenotypes in all subjects were cherry red spot (18.5%), hepatosplenomegaly (17.9%), coarse facies (15%), seizures (13.1%) and skeletal abnormalities (12.14%). Conclusions: Lysosomal storage disorders are considered to be one of the common causes in children with regression in learned skill, dysmorphic features and cherry red spot. Among these, glycolipid storage disorders are the most common, followed by mucopolysaccharidosis.
ABSTRACT
Objective: Clinicians are less familiar with clinical presentation of rare disorder like mucopolysaccharidosis (MPS), especially as presentation is complex and varied with different subtypes of this disorder. This case report highlights severe behavioural problems and non-recognition of MPS by clinicians. Though behavioural problems, hyperactivity and aggression are common in children suffering from mental disability, they are also seen in rare metabolic disorders like MPS. Methods: We have reported a seven year old girl who presented with severe episodes of hyperactivity, poor social interaction, impaired understanding of speech and delay as well as regression in developmental milestones is presented along with the investigations and treatment given. Results: Initially, the child was thought to be suffering from intellectual subnormality and/or pervasive developmental disorder. However, radiological studies showed x-ray findings suggestive of MPS. Her developmental history, physical findings, hearing loss as noted on BERA further supported this diagnosis. Due to financial constraints of the family detailed investigations (enzyme assays) to know the exact type of MPS could not be done. Behavioural problems had to be managed with low dose clonazepam and carbamazepine. Conclusion: It is worth considering metabolic disorders as one of the important differential diagnosis in any child presenting with developmental problems, dysmorphic facies along with behavioural problems.