First two unrelated cases of isolated sedoheptulokinase deficiency: A benign disorder?

We present the first two reported unrelated patients with an isolated sedoheptulokinase (SHPK) deficiency. The first patient presented with neonatal cholestasis, hypoglycemia, and anemia, while the second patient presented with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Both patients had elevated excretion of erythritol and sedoheptulose, and each had a homozygous nonsense mutation in SHPK. SHPK is an enzyme that phosphorylates sedoheptulose to sedoheptulose-7-phosphate, which is an important intermediate of the pentose phosphate pathway. It is questionable whether SHPK deficiency is a causal factor for the clinical phenotypes of our patients. This study illustrates the necessity of extensive functional and clinical workup for interpreting a novel variant, including nonsense variants.

Varicella complicated by cellulitis and deep vein thrombosis.

We report a 16-month-old girl with varicella complicated by cellulitis, invasive Group A Streptococcus (GAS) infection and deep vein thrombosis. She presented with varicella lesions, fever and a painful firm tumefaction on the right lower leg (RLL). Ultrasound showed a local subcutaneous tissue thickening suggestive of cellulitis and antibiotics were initiated. Further swelling of the RLL motivated a second ultrasound that showed an obstructive thrombus for which she was started on enoxaparin. The blood culture confirmed GAS infection leading to directed antibiotherapy. Additional studies showed positive lupus anticoagulant, decreased protein S and antithrombin. She completed a 2-week course of intravenous antibiotics and anticoagulation therapy with clinical and laboratory markers improvement. However, 3 days later, a recrudescence of symptoms occurred and the ultrasound revealed a local abscess. Further amoxicillin treatment resulted on a complete resolution of symptoms. Doppler ultrasound after 1 month showed markedly increased vein patency.

Recurrent elevated liver transaminases and acute liver failure in two siblings with novel bi-allelic mutations of NBAS.

BACKGROUND: Acute liver failure (ALF) in children can be life-threatening. Although many causes are known, ALF remains unexplained in about half of the cases. Recently, bi-allelic mutations in NBAS were reported to underlie recurrent episodes of elevated liver transaminases (ELT) and ALF in the context of diverse extrahepatic phenotypes. METHODS AND RESULTS: We here describe two sisters, born to non-consanguineous Portuguese parents, who had short stature and presented with recurrent episodes of severe ELT triggered by febrile respiratory viral infections since early childhood. Patient 1 had mild facial dysmorphism and died during the second ELT crisis at 3-11/12 years of age. Patient 2, currently 9 years old, had multiple episodes of ELT (>30), twice with ALF, often accompanied by extensive urticaria and facial angioedema. Whole-exome and Sanger sequencing revealed that both patients carried previously undescribed compound heterozygous mutations of NBAS (NM_015909.3): c.680A > C (p.His227Pro), affecting an evolutionarily conserved residue, and c.1749G > A (p.Trp583*), causing a premature stop codon. Both mutations are predicted to be highly damaging. The parents and two younger siblings are healthy and heterozygous for one or another mutant allele. CONCLUSION: The multiplex kindred reported herein expands the genotypic and phenotypic spectrum of this recently described clinical syndrome due to autosomal recessive NBAS deficiency.

Facilitação neuromuscular proprioceptiva (FNP) na miopatia mitocondrial: estudo de caso / Proprioceptive neuromuscular facilitation (PNF) on mitochondrial myopathy: case study

Introdução: As miopatias mitocondriais são consideradas um grupo de desordens que podem comprometer uma variedade de órgãos e apresentar fenótipos variáveis. Frequentemente afetam o sistema nervoso central e a musculatura esquelética e cardíaca. Objetivo: Investigar os efeitos de um programa individualizado, baseado nas técnicas de facilitação neuromuscular proprioceptiva (FNP), no gerenciamento da fraqueza muscular e habilidades funcionais de um paciente com miopatia mitocondrial de início tardio e distribuição atípica. Material e métodos: O paciente foi submetido a uma avaliação da força muscular e da capacidade funcional antes e após 12 semanas de tratamento, composto por exercícios de intensidade leve/moderada, com duração de 60 minutos/sessão e frequência de 2 atendimentos semanais. Resultados e Discussão: Ganhos relacionados à força muscular foram obtidos em determinados grupamentos musculares. O nível de independência funcional não sofreu alterações após a proposta terapêutica, entretanto manteve-se estabilizado. Conclusão: O programa reabilitativo atuou na minimização das complicações geradas pela fraqueza muscular e na otimização das atividades quotidianas. A reabilitação física faz-se necessária para um melhor gerenciamento da fraqueza muscular e da habilidade do paciente na execução de atividades básicas e instrumentais da vida diária.