Brazilian registry of patients with porphyria: REBRAPPO study.

BACKGROUND: Porphyrias are a rare group of disease due to inherited defects of heme synthesis with important systemic manifestations and great burden of disease for patients and families due to the exceptional course of disease with disabling chronic symptoms interposed by life-threatening acute attacks. Unfortunately, the porphyrias are usually underrecognized reflecting a lack of medical and disease awareness as well as few studies about natural history in large cohorts of patients. The main aim of this article is present consistent data about natural history and burden of disease in a large Brazilian cohort. METHODS: We conducted a national cross-sectional registry with retrospective clinical data of Brazilian patients with porphyria collected with Brazilian patients Association with Porphyria in collaboration with a tertiary care center for rare diseases. RESULTS: A cohort of 172 patients was analyzed in which 148 (86%) patients had the diagnosis of acute hepatic porphyria [AHP] that needed a mean of 62.04 medical visits and 9.6 years to achieve a definitive diagnosis. About AHP cohort, the most common first clinical manifestation were abdominal pain in 77 (52%) patients and acute muscle weakness in 23 (15.5%) with 73 (49.3%) patients presenting only one attack during disease course and 37 (25%) exhibiting 4 or more attacks in the last year. Of note, 105 patients with AHP reported chronic manifestations and the scores for quality of life are lower when compared with general healthy population. CONCLUSIONS: Brazilian patients with AHP had a higher prevalence of chronic disabling manifestations and a poor quality of life like other cohorts and a higher proportion of patients with recurrent attacks than previously reported.

Progressive spastic tetraplegia and axial hypotonia (STAHP) due to SOD1 deficiency: is it really a new entity?

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rare, progressive, and fatal neurodegenerative disease due to upper and lower motor neuron involvement with symptoms classically occurring in adulthood with an increasing recognition of juvenile presentations and childhood neurodegenerative disorders caused by genetic variants in genes related to Amyotrophic Lateral Sclerosis. The main objective of this study is detail clinical, radiological, neurophysiological, and genetic findings of a Brazilian cohort of patients with a recent described condition known as Spastic Tetraplegia and Axial Hypotonia (STAHP) due to SOD1 deficiency and compare with other cases described in the literature and discuss whether the clinical picture related to SOD1 protein deficiency is a new entity or may be represent a very early-onset form of Amyotrophic Lateral Sclerosis. METHODS: We conducted a case series report which included retrospective data from five Brazilian patients with SOD1 protein deficiency of a Brazilian reference center for Neuromuscular Disorders. Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population. RESULTS: All 5 patients presented with a childhood-onset neurodegenerative disorders characterized by spastic tetraplegia with axial hypotonia in all cases, with gestational history showing polyhydramnios in 4/5 and intrauterine growth restriction in 3/5 patients, with most patients initially presenting a normal motor development until the six month of life or during the first year followed by a rapidly progressive motor decline with severe dysphagia and respiratory insufficiency in all patients accompanied by cognitive impairment in 3/5 patients. All patients were homozygous for the c.335dupG (p.Cys112Trpfs*11) mutation in the SOD1 gene with completely decreased enzyme activity. CONCLUSIONS: This case series is the biggest data collection of the new recent clinical entity described as Spastic Tetraplegia and Axial Hypotonia (STAHP) due to SOD1 deficiency.