[Hepatic glycogen storage diseases: Symptoms, management and associated mutations]. / Enfermedades por depósito de glucógeno hepático: Clínica, manejo y mutaciones asociadas.

Glycogen storage diseases (GSD) are rare diseases derived from altered glycogen metabolism. This leads to glycogen storage in different organs such as muscle, kidney, and liver, resulting in a variety of clinical manifestations. GSD with liver involvement are classified into types I, III, IV, VI, and IX, depending on the enzymes affected. They are clinically characterized by hypoglycemia and hepato megaly as cardinal signs. Their diagnosis is initially based on clinical manifestations and laboratory test results. Nevertheless, diagnostic certainty requires a genetic study that identifies the specific mutation. Multiple mutations have been associated with each GSD. In Chile, since patients often lack the genetic study, the GSD genetic local characteristics are unknown. The treatment is based on dietary restrictions modulated according to the identified mutation. Today, the international consen sus indicates that early diagnosis allows better metabolic control and improves the patient's quality of life and prognosis. In this review, the information on GSD with liver involvement is updated to optimize the diagnosis, treatment, and follow-up of these patients, emphasizing specific nutritional and gastroenterological management.

Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy.

tRNA synthetase deficiencies are a growing group of genetic diseases associated with tissue-specific, mostly neurological, phenotypes. In cattle, cytosolic isoleucyl-tRNA synthetase (IARS) missense mutations cause hereditary weak calf syndrome. Exome sequencing in three unrelated individuals with severe prenatal-onset growth retardation, intellectual disability, and muscular hypotonia revealed biallelic mutations in IARS. Studies in yeast confirmed the pathogenicity of identified mutations. Two of the individuals had infantile hepatopathy with fibrosis and steatosis, leading in one to liver failure in the course of infections. Zinc deficiency was present in all affected individuals and supplementation with zinc showed a beneficial effect on growth in one.

Progressive neuromuscular disease in children with chronic cholestasis and vitamin E deficiency: clinical and muscle biopsy findings and treatment with alpha-tocopherol.

We have studied four children (ages 6 to 17 years) with chronic cholestasis who developed a slowly progressive neuromuscular disease characterized by ataxia, dysmetria, areflexia, loss of vibratory sensation, and a variable ophthalmoplegia. Serum vitamin E concentrations were low in all patients prior to treatment (0.17-2.0 mg/g cholesterol, normal greater than 3 mg/g). Muscle histochemical studies showed prominent yellow autofluorescence, basophilic cytoplasmic inclusions which stain with esterase and acid phosphatase, and occasional necrotic fibers. Ultrastructural findings consisted of increased number and size of membrane-bound dense bodies (lysosomes), membranous whorls, and autophagic vacuoles. Intramuscular injections of all-rac-alpha-tocopherol (0.55-1.42 mg/kg per 24 hours based on individualized pharmacokinetic data) were required in three patients to achieve normal serum vitamin E values. High-dose (32 mg/kg per 24 hours) oral supplementation was effective in one patient. After normalization of serum vitamin E concentrations for 12 to 20 months, the neurologic disease has improved in all four patients.