Macroglossia: A potentially severe complication of late‐onset Pompe disease

Abstract

Background Pompe disease is a rare neuromuscular disorder caused by a deficiency of a lysosomal enzyme, acid α‐glucosidase. Macroglossia is a classic clinical sign of several inherited myopathies and has also been reported to occur progressively in late‐onset Pompe disease (LOPD). Methods We describe patients with LOPD and macroglossia included in the French national Pompe disease registry. Clinical, functional, and radiological data were collected during periodic follow‐up and analyzed retrospectively. These cases were compared with 15 previously reported cases. Results Five patients, three females and two males, aged 71–88 years, were included in this study. All but one of the patients suffered from symptoms related to macroglossia before the diagnosis of Pompe disease. Three had localized tongue atrophy and one had significant localized tongue hypertrophy which led to glossectomy 10 years before diagnosis. Two patients had severe dysphagia, one of whom underwent gastrostomy for enteral nutritional support. One patient experienced the persistence of numerous sleep apneas despite nocturnal bilevel positive airway pressure (BiPAP) ventilation. All our patients had dysarthria, and two required speech therapy. Four patients had a tongue hypersignal on magnetic resonance imaging (MRI) T1 sequences. Conclusions Detection of macroglossia should be part of the clinical diagnosis and follow‐up of patients with LOPD, with a careful evaluation of its main consequences. Macroglossia can have severe functional impacts on speech, swallowing, and sleep. Whole‐body MRI with facial sections may facilitate the early diagnosis of Pompe disease with the “bright tongue sign”.

Characteristics of Patients With Late-Onset Pompe Disease in France

“…The clinical manifestations and severity of the disease do not seem to be different in this subgroup of patients, despite only half of these patients being heterozygous for the commonest mutation, vs approximately 90% of the total population studied. Dysphagia and speech impairment due to macroglossia are probably more frequent in this age range, as reported in a recent study, 20 and it will be important to increase the awareness of this among physicians.…”

“…We recently performed thorough investigations in patients complaining of dysphagia, which was found to be mostly related to macroglossia. 20 Most patients (67%) present a moderate increase in the CK level to levels that remain below 1,000 IU/L, with only 14% of patients having higher CK values of up to 2,723 IU/L. It is of interest that normal CK values have also been reported in 19% of patients, regardless of disease severity.…”

“…We recently performed thorough investigations in patients complaining of dysphagia, which was found to be mostly related to macroglossia. 20…”

Infant with macroglossia

“…The clinical photograph is not typical of the facies seen in Down syndrome. Macroglossia is typically seen as a late presentation of Pompe’s disease 3. Macroglossia in hypothyroidism is due to increased accumulation of subcutaneous glycosaminoglycans due to decreased degradation.…”

Clinical Neurology in Practice

“…5 Despite the fact that ALS usually leads to tongue atrophy, macroglossia may be observed in one-third of advanced forms of the disease (with long-term tracheostomy invasive ventilation, TIV), probably resulting in energy imbalance and abnormal fat accumulation due to both disease progression and excessive energy intake (using gastrostomy) in such patients; 6,7 macroglossia was also observed in 1 case of what was suspected to be primary lateral sclerosis. 8 Rarely, macroglossia has been described to occur in some inherited progressive muscular dystrophies, 9 such as Duchenne muscular dystrophy, 10 limb-girdle muscular dystrophy due to mutations of the FKRP gene, 11 Pompe's disease, 12,13 and in the Gipsy limb-girdle muscular dystrophies type 2C (C283Y homozygous mutation). 14 Finally, with 4 cases published in the medical literature, focal myositis of the tongue is also a very rare cause of macroglossia.…”