GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes.

Adult polyglucosan body disease (APBD) represents a complex autosomal recessive inherited neurometabolic disorder due to homozygous or compound heterozygous pathogenic variants in GBE1 gene, resulting in deficiency of glycogen-branching enzyme and secondary storage of glycogen in the form of polyglucosan bodies, involving the skeletal muscle, diaphragm, peripheral nerve (including autonomic fibers), brain white matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser extent heart, lung, kidney, and liver cells. The diversity of new clinical presentations regarding neuromuscular involvement is astonishing and transformed APBD in a key differential diagnosis of completely different clinical conditions, including axonal and demyelinating sensorimotor polyneuropathy, progressive spastic paraparesis, motor neuronopathy presentations, autonomic disturbances, leukodystrophies or even pure myopathic involvement with limb-girdle pattern of weakness. This review article aims to summarize the main clinical, biochemical, genetic, and diagnostic aspects regarding APBD with special focus on neuromuscular presentations.

[Hepatic glycogenosis: a case report]. / Glucogenosis hepá tica: a propósito de un caso.

The glycogen storage diseases contain a range of diseases that are characterized by the abnormal storage or utilization of glycogen, the organs most affected being muscle and / or liver. Hepatomegaly may be a clinical sign that could guide to the diagnosis. We describe a 15-year-old patient with hepatomegaly, hypertransaminasemia and growth retardation. He was diagnosed with a glycogen storage disease by liver biopsy.

Glucogenosis hepática: a propósito de un caso / Hepatic glycogenosis: a case report

RESUMEN Las glucogenosis abarcan un rango de enfermedades que se caracterizan por el almacenamiento o utilización anormal del glucógeno, siendo los órganos más afectados el músculo y/o el hígado. La hepatomegalia puede ser un signo clínico que guie al diagnóstico. Describimos a un paciente de 15 años de edad con hepatomegalia, hipertransaminasemia y retraso del crecimiento, a quien se le diagnosticó glucogenosis por biopsia hepática.

ABSTRACT The glycogen storage diseases contain a range of diseases that are characterized by the abnormal storage or utilization of glycogen, the organs most affected being muscle and / or liver. Hepatomegaly may be a clinical sign that could guide to the diagnosis. We describe a 15-year-old patient with hepatomegaly, hypertransaminasemia and growth retardation. He was diagnosed with a glycogen storage disease by liver biopsy.

Hepatic glycogen storage diseases are associated to microbial dysbiosis.

INTRODUCTION: The gut microbiome has been related to several features present in Glycogen Storage Diseases (GSD) patients including obesity, inflammatory bowel disease (IBD) and liver disease. OBJECTIVES: The primary objective of this study was to investigate associations between GSD and the gut microbiota. METHODS: Twenty-four GSD patients on treatment with uncooked cornstarch (UCCS), and 16 healthy controls had their faecal microbiota evaluated through 16S rRNA gene sequencing. Patients and controls were ≥3 years of age and not on antibiotics. Faecal pH, calprotectin, mean daily nutrient intake and current medications were recorded and correlated with gut microbiome. RESULTS: Patients' group presented higher intake of UCCS, higher prevalence of IBD (n = 04/24) and obesity/overweight (n = 18/24) compared to controls (n = 0 and 06/16, respectively). Both groups differed regarding diet (in patients, the calories' source was mainly the UCSS, and the intake of fat, calcium, sodium, and vitamins was lower than in controls), use of angiotensin-converting enzyme inhibitors (patients = 11, controls = 0; p-value = 0.001) multivitamins (patients = 22, controls = 01; p-value = 0.001), and mean faecal pH (patients = 6.23; controls = 7.41; p = 0.001). The GSD microbiome was characterized by low diversity and distinct microbial structure. The operational taxonomic unit (OTU) abundance was significantly influenced by faecal pH (r = 0.77; p = 6.8e-09), total carbohydrate (r = -0.6; p = 4.8e-05) and sugar (r = 0.057; p = 0.00013) intakes. CONCLUSIONS: GSD patients presented intestinal dysbiosis, showing low faecal microbial diversity in comparison with healthy controls. Those findings might be due to the disease per se, and/or to the different diets, use of UCSS and of medicines, and obesity rate found in patients. Although the main driver of these differences is unknown, this study might help to understand how the nutritional management affects GSD patients.

Teste de esforço cardiopulmonar na avaliaçäo de doenças musculares / Cardiopulmonary exercise testing for evaluation of muscle diseases

Objetivo: Analisar o teste de esforço cardiopulmonar (TECP) no diagnóstico de miopatias. Métodos: 27 pacientes com miopatia realizaram TECP (protocolo de bicicleta em rampa, máximo, interrompido por sintoma). Resultados: Pacientes distróficos e pacientes com mitocondriopatias mostraram diferenças significativas em relaçao aos controles para as variáveis potência do trabalho desenvolvido (watt) e pico do consumo de oxigênio (VO2máx). Pacientes com mitocondriopatias mostraram diminuiçao significativa do limiar anaeróbio em relaçao aos controles, além de elevaçao dos valores do quociente respiratório (QR) do pico do exercício em relaçao aos demais grupos. Conclusoes: TECP pode ser útil na avaliaçao evolutiva do grau de limitaçao física dos pacientes com miopatia. As variáveis potência do trabalho desenvolvido, VO2 máx, limiar anaeróbio e QR do pico do exercício podem sugerir o diagnóstico de miopatia e seus subtipos, excluindo quadros psicológicos.

Glicogenose hepática na infância: achados clínicos e laboratoriais em 20 pacientes / Hepatic glycogenosis in childhood: clinical and laboratory findings in 20 patients

Foram estudadas 20 crianças com quadro clínico e exames laboratoriais de glicogenose hepática. Catorze eram do sexo masculino e seis do feminino. Em relaçao à idade de início dos sintomas, notou-se variaçao desde o nascimento até 24 meses e em relaçao à idade do diganóstico, a variaçao foi de dois a 81 meses. A hepatomegalia foi encontrada em todos os pacientes, a diarréia em 65 por cento deles (13/20) e crises convulsivas em 50 por cento (10/20). A avaliaçao nutricional mostrou maior comprometimento da estatura que do peso. Nos achados laboratoriais destacaram-se a elevaçao das transaminases hepáticas (12/19), a hipercolesterolemia (8/14), a hiperuricemia (6/17) e a hipoglicemia (6/20). A funçao hepática nao estava comprometida na maioria dos casos. No teste do glucagon a resposta foi variável. O estudo histoenzimológico, realizado em 15 pacientes, mostrou os seguintes achados: Tipo VI (déficit de fosforilase) em sete pacientes, Tipo I (déficit de glicose-6-fosfatase) em dois pacientes, Tipo IV (déficit da enzima ramificadora) em um paciente e em cinco pacientes o estudo nao permitiu a classificaçao. O achado de hipoglicemia em poucos pacientes pode ser explicado pelo pequeno número de glicogenose Tipo I neste estudo, provavelmente devido ao fato de que este tipo é o de diagnóstico mais fácil, com menor necessidade de encaminhamento a serviços especializados.

[Hepatic glycogenosis in childhood: clinical and laboratory findings in 20 patients]. / Glicogenose hepática na infância: achados clínicos e laboratoriais em 20 pacientes.

We studied 20 children with a clinical picture and laboratory study suggestive of hepatic glycogenosis. The age of the beginning of symptoms varied from birth to 24 months and the age at the diagnosis varied from 2 to 81 months. Hepatomegaly was found in all patients, diarrhea in 65% (13/26), "doll-face" in 55% (11/20) and convulsions in 50% (10/20). Nutritional evaluation showed more height deficiency than weight deficiency. Laboratory tests showed elevation of hepatic transaminases (12/19), hypercolesterolemia (8/14), hyperuricemia (6/17) and hypoglycemia (6/20). Liver function was not compromised in most of the cases. The results of glucagon tolerance test were variable. The histoenzymology study performed in 15 patients revealed the following results: Type VI (liver phosphorylase deficiency) in seven, Type I (glucose-6-phosphatase deficiency) in two, Type IV (brancher enzyme) in one and no conclusion could be drawn in five patients. The finding of hypoglycemia in few cases of this study can be justified by the few number of glycogenosis Type I, probably due to the fact that this type is the most easily diagnosed, with less necessity of referring them to specialized centers.

Síndrome de Fanconi-Bickel / Fanconi-Bickel syndrome

Se presenta el caso de un niño de un año tres meses de edad con síndrome de Fanconi-Bickel, caracterizado por las manifestaciones del síndrome de Fanconi (glucosuria, aminoaciduria y fosfaturia) y acúmulo de glucógeno en el hígado semejante a lo que se observa en la glucogenosis tipo Ia. Debido a la presencia de glucogenosis hepática el paciente también presentó hipoglucemia, cetonuria, hipercolesterolemia e hipertrigliceridemia. La glucogenosis observada en los pacientes con síndrome de Fanconi-Bickel, no depende de defecto de la actividad de la glucosa-6-fosfatasa, sino al parecer, de un defecto del transportador que moviliza la glucosa y la galactosa en el hígado y en la membrana basolateral del túbulo proximal del nefrón

[Glycogenosis type II, infantile variant. Report of a case and review of the literature]. / Glucogenosis tipo II variedad infantil. Informe de un caso y revisión de la literatura.

A case of glycogenosis type II infantile onset (Pompe's disease) is presented, and the literature is reviewed in order to establish the basis of the diagnostic suspect. We studied an 8-month old female with muscular weakness--and cardiac failure. The chest X-ray: cardiomegaly; electrocardiogram: PR interval of 0.06 seconds, gigant QRS complexes, biventricular hypertrophy, and the echocardiogram and cineangiography: left ventricle hypertrophy and hypokinesia. The patient died because of refractory heart failure. Histochemical examination demonstrated excessive intracellular accumulation of glycogen. Also, in the muscle, the kidneys and the liver we did not find any alpha 1,4 glucosidase. Then, the diagnosis of glycogenosis type II infantile onset was established. Finally, we conclude that this disease should be suspected in every infant with muscular weakness, cardiac failure, cardiomegaly, electrocardiogram with shortness of PR interval, gigant QRS complexes and biventricular hypertrophy, and that needs to be confirmed by muscle biopsy. At the moment, there has not been reported any case of Pompe's disease in the Mexican literature.

Myopathy and growth failure in debrancher enzyme deficiency: improvement with high-protein nocturnal enteral therapy.

Seven patients with debrancher enzyme deficiency and childhood or adolescent onset myopathy, four of whom also had growth failure, received long-term treatment consisting of high-protein enteral infusion overnight and high-protein feeds during the day for periods varying from 8 to 42 months. All patients demonstrated improvement in physical activity and endurance. Improvement in muscle strength was documented in five patients, with reversal of myopathic EMG patterns to normal in two patients and reversal of abnormal ECG findings to normal in one patient. All four patients with growth failure showed dramatic improvement in growth rates. This positive response to high-protein enteral therapy supports the concept that myopathy in debrancher enzyme deficiency is at least partly the result of reversible muscle amino acid depletion.