Late Onset Pompe Disease with Novel Mutations and Atypical Phenotypes.

BACKGROUND: Late onset Pompe disease (LOPD) is rare and generally manifests predominantly as progressive limb girdle muscle weakness. It is linked to the pathogenic mutations in GAA gene, which leads to glycogen accumulation in various tissues. MATERIALS AND METHODS: We describe the unusual clinical, biochemical, histopathological and genetic characteristics of 5 cases of LOPD. RESULTS: The first case had progressive anterior horn cell like disease (AHCD) that evolved later to classical limb girdle syndrome and respiratory failure, the second patient had rigid spine syndrome with gastrointestinal manifestations, the third had limb girdle weakness superimposed with episodic prolonged worsening and respiratory failure, the fourth had large fibre sensory neuropathy without primary muscle involvement and the fifth presented with classical limb girdle muscle weakness. Two homozygous missense mutations c.1461C > A (p.Phe487Leu) and c.1082C > T (p.Pro361Leu) in the GAA gene were identified in case 1 and 2 respectively. Case 3 was compound heterozygous with inframe c.1935_1940del (p.Val646_Cys647del) and an intronic splice effecting variant c.-32-13T > G. Compound heterozygous missense variants c.971C > T (p.Pro324Leu) and c.794G > A (p.Ser265Asn) were identified in case 4. Case 5 had a frameshift insertion c.1396dupG (p.Val466GlyfsTer40) and a synonymous splice affecting variant c.546G > T(p.Thr182=). CONCLUSION: We are describing for the first time from India on LOPD with unusual phenotypes identified. A high degree of clinical suspicion and diagnosing rare phenotypes of Pompe disease is imperative to consider early initiation of Enzyme Replacement Therapy (ERT).

Nonneoplastic Cystic Lesions of the Central Nervous System-Histomorphological Spectrum: A Study of 538 Cases.

Background A wide spectrum of non-neoplastic cystic lesions can occur in the central nervous system (CNS). These are uncommon, benign and of diverse aetiology, pathogenesis and clinical presentation.The spectrum of these lesion varies based on the location and in turn histogenesis. Objectives To evaluate the pathologic spectrum of non-neoplastic cystic lesions in the CNS (both developmental and acquired) and highlight the role of histopathology in the diagnosis of these cystic lesions. Settings and Design This was a retrospective study done at Department of Neuropathology,NIMHANS. Materials and Methods All the histologically diagnosed non-neoplastic cystic lesions of CNS submitted to the Department of Neuropathology between 2014 and 2017 were reviewed in this study. The data was analysed in relation to the type of cysts, location(intracranial and spinal), and clinical profile using SPSS software version 17.0. Results The study included 538 cases with patient age ranging from 5 months to 90 years [M:F:1:1.05]. Non-infective cysts (489/538, 90.8%) predominated over the infective cysts (49/539, 9.2%) with epidermoid cysts (132/538, 24.5%) being the most frequent one followed by colloid cysts (126/538, 23.4%) and arachnoid cysts (111/538,20.6%). The most common infective cyst was neurocysticercosis (42/538, 7.8%) followed by hydatid cyst (7/538, 1.3%). Intracranial cysts (415/538, 77.1%) were more common than spinal ones (123/538, 22.9%). Conclusions: A variety of cystic lesions occur in the CNS with overlapping clinical features, image findings and lining. Hence, histological analysis plays a crucial role in the evaluation of these lesions.