Diagnostic accuracy and the first genotype-phenotype correlation in glycogen storage disease type V.

BACKGROUND: Glycogen storage disease type V (GSDV) is an autosomal recessive metabolic condition caused by pathogenic PYGM variants. This is an underdiagnosed condition as it presents with exercise intolerance in children. We reviewed the GSDV cases of a tertiary hospital center to assess diagnostic timing/accuracy, as well as potential clinical/analytical predictors of such factors. METHODS: We retrospectively reviewed all GSDV cases with follow-up in both Pediatric and Adult Metabolic Diseases consultations. We included 28 cases and assessed their hospital record for clinical information. RESULTS: Over 90% of our cases had late diagnoses, with more than 50% being diagnosed in adulthood despite symptom onset in preschool (very late diagnosis). Diagnostic age was lower in patients exhibiting myoglobinuria. Interestingly, patients with a positive family history of GSDV had similar rates of very late diagnoses, likely since the index case was already detected very late in life. Finally, we observe that the R50* variant is associated with increased myoglobinuria and CK elevation, in a dosage-dependent manner. CONCLUSION: We concluded that GSDV is severely underdiagnosed, and that some clinical and analytical aspects of the condition can be more indicative of this diagnosis. Furthermore, we propose for the first time a genotype-phenotype correlation in GSDV. IMPACT: GSDV is a pediatric-onset metabolic disorder that is mostly diagnosed late in the adult age and commonly misdiagnosed. We observed the first genotype-phenotype correlation in GSDV, regarding the common R50* variant. Awareness of GSDV for pediatricians and the overall medical community is vital.

Tracheitis - A Rare Extra-Intestinal Manifestation of Ulcerative Colitis in Children.

INTRODUCTION: Inflammatory bowel disease may cause both intestinal and extraintestinal manifestations. Respiratory symptoms in ulcerative colitis are rare and tracheal involvement is exceedingly rare in children. CASE 1: Sixteen year-old female with a 4-week-complaint of abdominal pain, bloody diarrhea, fever and cough. The investigation was consistent with the diagnosis of concomitant ulcerative colitis/coinfection to Escherichia coli. On day 4 respiratory signs persisted so azithromycin and inhaled corticosteroids were added. By day 6 she progressed to respiratory failure and was diagnosed with necrotic tracheitis so started on intravenous steroids with fast clinical improvement. CASE 2: Twelve-year-old male adolescent with ulcerative colitis and sclerosing cholangitis started dry cough and throat pain 10 days after diagnosis. Laboratory investigations showed increased inflammatory signs and normal chest X-ray. He started treatment with azithromycin without clinical improvement and on day five he presented dyspnea and fever. Laryngeal fibroscopy suggested tracheitis and so systemic steroids where added with fast clinical and analytic improvement. DISCUSSION: Tracheitis should be suspected if there are persistent respiratory symptoms even when exams are normal. Early recognition and early treatment are essential for a good prognosis preventing progression to respiratory failure.

INTRODUÇÃO: A doença inflamatória intestinal pode ser causa de complicações intestinais e extraintestinais. As manifestações respiratórias de colite ulcerosa são raras e o envolvimento traqueal é extremamente raro em crianças. CASO 1: Adolescente do sexo feminino, de dezasseis anos de idade, com queixas de dor abdominal, diarreia sanguinolenta, febre e tosse seca com 4 semanas de evolução. A investigação realizada foi compatível com o diagnóstico de colite ulcerosa/co-infecção a Escherichia coli. No 4ª dia de internamento, por persistência das queixas respiratórias, iniciou azitromicina e corticoterapia inalada. Dois dias mais tarde evoluiu para insuficiência respiratória; foi-lhe diagnosticada traqueíte necrotizante pelo que iniciou corticóides endovenosos com rápida melhora clínica. CASO 2: Adolescente do sexo masculino de 12 anos de idade com colite ulcerosa e colangite esclerosante que inicia queixas de odinofagia e tosse seca 10 dias após o diagnóstico. O estudo analítico revelou aumento dos parâmetros inflamatórios e radiografia de tórax normal. Nesta altura inicia azitromicina, sem melhora clínica, iniciando, no quinto dia de doença, dispnéia e febre. A fibroscopia laríngea foi sugestiva de traqueíte pelo que iniciou corticoterapia sistémica com rápida melhoria clínica e analítica. DISCUSSÃO: A traqueíte é uma entidade que deve ser equacionada em doentes com doença inflamatória intestinal na presença de sintomas respiratórios persistentes, mesmo com estudo complementar normal. O seu reconhecimento e tratamento precoces são essenciais para um prognóstico favorável e prevenção da progressão para insuficiência respiratória.