A novel neuromuscular form of glycogen storage disease type IV with arthrogryposis, spinal stiffness and rare polyglucosan bodies in muscle.

Glycogen storage disease type IV (GSD IV) is an autosomal recessive disorder causing polyglucosan storage in various tissues. Neuromuscular forms present with fetal akinesia deformation sequence, lethal myopathy, or mild hypotonia and weakness. A 3-year-old boy presented with arthrogryposis, motor developmental delay, weakness, and rigid spine. Whole body MRI revealed fibroadipose muscle replacement but sparing of the sartorius, gracilis, adductor longus and vastus intermedialis muscles. Polyglucosan bodies were identified in muscle, and GBE1 gene analysis revealed two pathogenic variants. We describe a novel neuromuscular GSD IV phenotype and confirm the importance of muscle morphological studies in early onset neuromuscular disorders.

Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies.

OBJECTIVE: Exome sequencing is a successful option for diagnosing individuals with previously uncharacterized genetic conditions, however little has been reported regarding its utility in a prenatal setting. The goal of this study is to describe the results from a cohort of fetuses for which exome sequencing was performed. METHODS: We performed a retrospective analysis of the first seven cases referred to our laboratory for exome sequencing following fetal demise or termination of pregnancy. All seven pregnancies had multiple congenital anomalies identified by level II ultrasound. Exome sequencing was performed on trios using cultured amniocytes or products of conception from the affected fetuses. RESULTS: Relevant alterations were identified in more than half of the cases (4/7). Three of the four were categorized as 'positive' results, and one of the four was categorized as a 'likely positive' result. The provided diagnoses included osteogenesis imperfecta II (COL1A2), glycogen storage disease IV (GBE1), oral-facial-digital syndrome 1 (OFD1), and RAPSN-associated fetal akinesia deformation sequence. CONCLUSION: This data suggests that exome sequencing is likely to be a valuable diagnostic testing option for pregnancies with multiple congenital anomalies detected by prenatal ultrasound; however, additional studies with larger cohorts of affected pregnancies are necessary to confirm these findings.

Liver-spleen scintigraphy in glycogen storage disease (glycogenoses).

Some forms of glycogen storage disease (GSD) primarily affect the liver, including types I, III, IV, VI, IX and 0. Scanning with Tc-99m sulfur colloid, while not being specific, does reveal some characteristic features. Most experience is with scanning in type I disease, though there are few reports in the literature. Six patients with type I, type III, type IV, and probably type VI disease are presented in this report. GSD should be considered in infants and young children presenting with hepatomegaly and abnormal liver-spleen scans. Sequential imaging is useful in following these patients. When focal defects are present, long term follow-up is indicated to detect hepatocellular adenocarcinoma.

Radiography of glycogen storage diseases.

Sixty-three patients with glycogen storage disease were evaluated. Findings on plain film examinations, excretory urography, barium gastrointestinal studies, ultrasonography, and angiography were categorized by type of glycogen storage disease. In type I findings include hepatomegaly with hepatic dysfunction, renomegaly with an increased incidence of renal calculi, and osteopenia with various associated osseous abnormalities. These changes were less pronounced in types III, IV, and VI. Type II displayed either cardiac or skeletal muscle glycogen deposition. Correlation with postmortem examination in 14 individuals is given.

[Mucoviscidosis: dysporia entero-broncho-pancreatica congenita familiaris (Glanzmann): Anderson syndrome (author's transl)]. / Mucoviscidose, sive: Dysporia entero-broncho-pancreatica congenita familiaris (Glanzmann), sive Andersen-Syndrom. (Verlaufsbeobachtung über 10 Jahre).

The features of dysporia entero-broncho-pancreatica familiaris (mucoviscidosis) are described and the course of the disease over ten years is recounted. The cases are probably patients with true mucoviscidosis but in whom not all the symptoms develop in early childhood (Doerr). In the present case the symptoms only developed at the age of five years. From this time on there was increasing pancreatic insufficiency, chronic recurring bronchitis, with increasing destructive bronchitis and resulting respiratory insufficiency, dyspnoea and orthopnoea, right heart strain, sodium and chloride loss in the sweat, changes in the duodenum and the development of aganglionic megacolon.