Clinical practice guidelines for glycogen storage disease V & VII (McArdle disease and Tarui disease) from an international study group

Supplementary material is available online at https://www.sciencedirect.com/science/article/pii/S0960896621006878#sec0054 .Highlights: • Management of physical activity intolerance in GSD V and GSD VII is nuanced and impacts activities of daily living (ADL). • Guidelines support clinicians in multiple disciplines across the continuum of care and lifespan of patients. • Overview of management, including guidance on physical activity, nutrition, pain, medical emergencies, and rehabilitation. • Considerations for general medical care, including established and emerging concomitant conditions, potential drug-disease interactions, surgery, and obstetrics. • Emerging issues and knowledge gaps are highlighted.Reneo Pharmaceuticals Inc.; International Association for Muscle Glycogen Storage Disease

Normoglycemic ketonemia as biochemical presentation in ketotic glycogen storage disease

Background: According to the textbooks, the ketotic glycogen storage disease (GSD) types 0, III, VI, IX, and XI are associated with fasting ketotic hypoglycemia and considered milder as gluconeogenesis is intact. Methods: A retrospective cohort study of biochemical profiles from supervised clinical fasting studies is performed in ketotic GSD patients in our metabolic center. For data analysis, hypoglycemia was defined as plasma glucose concentration <2.6 mmol/L. Total KB was defined as the sum of blood acetoacetate and β-hydroxybutyrate concentrations. If the product of glucose and KB concentrations was greater than 10, a ketolysis defect was suspected. Results: Data could be collected from 13 fasting studies in 12 patients with GSD III (n = 4), GSD VI (n = 3), and GSD IX (n = 5). Six patients remained normoglycemic with median glucose concentration of 3.9 mmol/L (range, 2.8–4.6 mmol/L) and median total KB concentration of 1.9 mmol/L (range, 0.6–5.1 mmol/L). The normoglycemic patients included type VI (3 out of 3) and type IX (3 out of 5) patients. All type III patients developed ketotic hypoglycemia. Interestingly, in five patients (one GSD III, one GSD VI, and three GSD IX), the biochemical profile suggested a ketolysis defect. Conclusion: Normoglycemic ketonemia is a common biochemical presentation in patients with GSD types VI and IX, and ketonemia can precede hypoglycemia in all studied GSD types. Therefore, GSD VI and GSD IX should be added to the differential diagnosis of ketotic normoglycemia, and KB concentrations should be routinely measured in ketotic GSD patients

Hearing in adults with Pompe disease

Hearing loss has been recognized as an important cause of morbidity in infants with Pompe disease, a metabolic disorder caused by deficiency of acid α-glucosidase. It is unknown whether hearing is also affected in adult Pompe patients. We have studied the prevalence, severity, and type of hearing loss in 58 adult patients using tympanometry and pure-tone audiometry. Compared to normative data (International Organisation for Standardisation standard 7029), 72% of patients had impaired hearing thresholds at one or more frequencies in at least one ear. All measured frequencies were equally affected. All patients had a sensorineural type of hearing loss, pointing to cochlear or retrocochlear pathology. Categorised according to the standards of the World Health Organisation 21% of patients had a clinically relevant hearing loss (16% slight, 3% moderate, 2% profound). Though this suggests that hearing loss occurs in a considerable number of patients with Pompe disease, this prevalence is similar to that in the general population. Therefore, we conclude that hearing loss is not a specific feature of Pompe disease in adults

High cardiovascular morbidity and mortality in myofibrillar myopathies due to DES gene mutations: a 10-year longitudinal study.

To determine incidence and type of major cardiac adverse events in patients with mutated desmin (DES) gene, we retrospectively reviewed baseline medical information, and examined the long-term outcomes of 28 DES patients (17 men, baseline mean age=37.7±14.4 years [min=9, max=71]) from 19 families. Baseline studies revealed skeletal muscle involvement in 21 patients and cardiac abnormalities in all but one patient. Over a mean follow-up of 10.4±9.4 years [min=1, max=35], cardiac death occurred in three patients, death due to cardiac comorbidities in two, one or more major cardiac adverse events in 13 patients. Among the 19 patients with mild conduction defects at baseline, eight developed high-degree conduction blocks requiring permanent pacing. Cardiac involvement was neither correlated with the type of DES mutation nor with the severity of skeletal muscle involvement. Our study underscores that in DES patients in-depth cardiac investigations are needed to prevent cardiac conduction system disease

Un diabète particulièrement compliqué

International audienc

Un diabète particulièrement compliqué

International audienceIntroductionLaminopathies (diseases related to A/C mutations of lamines) are rare genetic diseases with an extensive phenotypic spectrum, including lipodystrophic syndromes—characterized by a selective loss of adipose tissue—of which the partial Dunnigan family type is the most frequent.Case reportWe report on a 55-year-old woman with diabetes and long-term disabling myalgia. Her cushingoid morphotype, associated with cutaneous lipo-atrophy and muscle hypertrophy in addition to a genetic heritage, led us to the diagnosis of complex partial familial lipodystrophy heterozygous LMNA_c.82C>T, p.Arg28Trp mutation.ConclusionFamilial partial lipodystrophic syndromes may have varied phenotypes, mainly cardio-metabolic, which could mimic a particularly severe type 2 diabetes. The diagnostic work-up of this disease has to include a careful investigation of gait troubles and paroxysmal conduction that could lead to sudden death, as well as a genetic examination. In some cases, recombinant leptin can be proposed.IntroductionLes laminopathies (maladies liées aux mutations des lamines A/C) sont des maladies génétiques rares, au spectre phénotypique étendu, incluant les syndromes lipodystrophiques (se caractérisant par une perte sélective de tissu adipeux), dont la forme familiale partielle de type Dunnigan est la plus fréquente.ObservationIl s’agit d’une patiente âgée de 55 ans, atteinte d’un diabète, rapportant de longue date des myalgies invalidantes. Son morphotype cushingoïde associé à une lipo-atrophie cutanée et à une hypertrophie musculaire, avec notion d’atteinte familiale, nous a conduit au diagnostic de lipodystrophie familiale partielle complexe avec mutation hétérozygote c.82C>T, p.Arg28Trp dans le gène LMNA.ConclusionLes syndromes lipodystrophiques partiels d’origine familiale peuvent revêtir des phénotypes variés, à dominance cardio-métabolique, pouvant mimer un diabète de type 2 particulièrement sévère. La prise en charge doit comporter la recherche attentive de troubles du rythme et/ou de la conduction paroxystique pourvoyeur de mort subite, ainsi qu’un conseil génétique. La leptine recombinante peut parfois être proposée