Scipedia: Collection of Molecular Genetics and Metabolism Reports

Atypical presentation of mucopolysaccharidosis type IVA

Scipedia content — Thu, 20 Oct 2016 16:44:41 +0200

A 14 year old patient with short stature, type I diabetes, and cataracts was referred for evaluation of avascular necrosis of the femoral head. Radiography was suggestive of spondyloepiphyseal dysplasia with decreased bone mineral density for age. Targeted molecular and biochemical testing were normal in this patient. Whole exome sequencing was performed and showed compound heterozygosity for previously reported pathogenic GALNS variants which were diagnostic of mucopolysaccharidosis, type IVA (Morquio A). While this case describes neither a novel condition nor a new mutation, it does illustrate three important points in the diagnosis of patients with atypical forms of MPS IVA. First, that in many instances urine glycosaminoglycan analysis is not sufficient to rule out MPS IVA as a potential diagnosis. Patients in whom biochemical screening is advised should have measurement of leukocyte enzymatic activity. Second, that in patients with radiographic evidence of spondyloepiphyseal dysplasia with additional features or with normal targeted testing, MPS IVA should remain in the differential diagnosis. Third, that whole exome sequencing represents a viable diagnostic platform for evaluation of patients with unknown skeletal or metabolic disease.

Successful pregnancy and delivery in a woman with propionic acidemia from the Amish community

Scipedia content — Thu, 20 Oct 2016 16:44:38 +0200

Propionic acidemia (PA) is an inborn error of protein metabolism with a variable clinical presentation ranging from neonatal encephalopathy to seemingly asymptomatic individuals who present with cardiomyopathy or sudden death. PA is recognized in the Amish population, often with an early asymptomatic course and eventual cardiac complications. Thus, Amish women with PA may reach reproductive age without clinical sequelae, but are at increased risk for metabolic decompensation during pregnancy, delivery and postpartum period. We describe the care of an Amish woman with PA during her first pregnancy and delivery.

Autosomal dominant Carvajal plus syndrome due to the novel desmoplakin mutation c.1678A > T (p.Ile560Phe)

Scipedia content — Thu, 20 Oct 2016 16:44:35 +0200

Carvajal syndrome is an autosomal dominant or autosomal recessive disorder, manifesting with dilated cardiomyopathy, woolly hair, and palmoplantar keratoma. Additional manifestations can be occasionally found. Carvajal syndrome may be due to mutations in the desmocollin-2, desmoplakin, or plakophilin-2 gene. We report a family with Carvajal syndrome which additionally presented with hypoacusis, noncompaction, recurrent pharyngeal infections, oligodontia, and recurrent diarrhoea. Father and brother were also affected and had died suddenly, the father despite implantation of a cardioverter defibrillator (ICD). Genetic studies revealed the novel pathogenic mutation c.1678A > T in the desmoplakin gene resulting in the amino acid change Ile to Phe at position 560 in the index case and her brother. The index case underwent ICD implantation recently. Phenotypic manifestations of Carvajal syndrome are even broader than so far anticipated, the number of mutations in the desmoplakin gene responsible for Carvajal syndrome is still increasing, and these patients require implantation of an ICD as soon as their diagnosis is established.

Assessment of the phenotype genotype variability and correlation in m.3243A > G mutation carriers requires prospective studies

Scipedia content — Thu, 20 Oct 2016 16:44:32 +0200

Response to: Letter to the Editor Regarding: The Expanding Phenotype of MELAS Caused by the m.3291 T > C tRNA Mutation E Kelland, C. A. Rupar, Asuri N. Prasad, K. Y. Tay, A. Downie and C. Prasad (1) by Josef Finsterer, MD, PhD [1], Sinda Zarrouk-Mahjoub, PhD [2] [1] Krankenanstalt Rudolfstiftung, Vienna [2] Genomics Platform, Pasteur Institute of Tunis, Tunisia

Scipedia content — Thu, 20 Oct 2016 16:44:29 +0200

Hypothyroidism in late-onset Pompe disease

Scipedia content — Thu, 20 Oct 2016 16:44:25 +0200

In Pompe disease, a deficiency of acid α-glucosidase enzyme activity leads to pathologic accumulation of glycogen in tissues. Phenotype heterogeneity in Pompe includes an infantile form and late-onset forms (juvenile- and adult-onset forms). Symptoms common to all phenotypes include progressive muscle weakness and worsening respiratory function. Patients with late-onset forms of Pompe disease commonly complain of chronic fatigue and generalized muscle weakness prior to being diagnosed with Pompe disease, and this may lead to consideration of hypothyroidism in the differential diagnosis. This study aimed to evaluate the prevalence of hypothyroidism in the adult-onset form of Pompe disease. Electronic chart review was performed at the Advanced Therapies Clinic at the University of Minnesota Medical Center (UMMC) to identify patients with late-onset Pompe disease. The identified charts were reviewed for a co-diagnosis of hypothyroidism. A query was made to the clinical data repository at UMMC searching diagnosis ICD9 code 244.9 (hypothyroidism not otherwise specified) and/or presence of levothyroxine from 2011 to 2014 in patients 18 years of age and older. The clinical data repository found a prevalence of hypothyroidism of 3.15% (56,072 of 1,782,720 patients) in the adult patient population at UMMC. Ten adult patients with Pompe disease were identified, five with the diagnosis of hypothyroidism (50%, 95% CI: 23.7, 76.3, p