Late Onset Pompe Disease with Novel Mutations and Atypical Phenotypes

J Neuromuscul Dis. 2021 Nov 30. doi: 10.3233/JND-210728.

PMID: 34864681

Tanushree Chawla, Veeramani Preethish-Kumar, Kiran Polavarapu

Highlights: This study describes the unusual clinical, biochemical, histopathological and genetic characteristics of 5 cases of LOPD.

Abstract

Background: Late-onset Pompe disease (LOPD) is an uncommon condition that causes increasing limb girdle muscular weakening. It's linked to pathogenic mutations in the GAA gene, which cause glycogen to build up in different tissues.

Materials and methods: Five cases with LOPD were studied for their distinctive clinical, biochemical, histopathological, and genetic characteristics.

Results: The first patient had progressive anterior horn cell like disease (AHCD) that progressed to classical limb girdle syndrome and respiratory failure, the second had rigid spine syndrome with gastrointestinal manifestations, the third had limb girdle weakness with episodic prolonged worsening and respiratory failure, the fourth had large fibre sensory neuropathy without primary muscle involvement, and the fifth had classical limb girdle muscle weakness. In cases 1 and 2, homozygous missense mutations c.1461C > A (p.Phe487Leu) and c.1082C > T (p.Pro361Leu) in the GAA gene were found. Case 3 was compound heterozygous for an intronic splice affecting variation c.-32-13T > G and an inframe c.1935_1940del (p.Val646_Cys647del). Case 4 revealed compound heterozygous missense variants c.971C > T (p.Pro324Leu) and c.794G > A (p.Ser265Asn). Case 5 had c.1396dupG (p.Val466GlyfsTer40) frameshift insertion and a synonymous splice affecting variant c.546G > T(p.Thr182=).

Conclusion: For the first time, we describe a LOPD variant from India with unusual phenotypes. To consider early beginning of Enzyme Replacement Therapy, a high level of clinical suspicion and detecting unusual phenotypes of Pompe disease are required (ERT).

Keywords: LOPD, Pompe disease, Rigid spine, anterior horn cell, late-onset Pompe disease, peripheral neuropathy