Mild Phenotype of Arthrogryposis, Renal Dysfunction, and Cholestasis Syndrome 1 Caused by a Novel VPS33B Variant.

The arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is an autosomal recessive multisystem disease caused by variants in VPS33B or VIPAS39. The classical presentation includes congenital joint contractures, renal tubular dysfunction, cholestasis, and early death. Additional features include ichthyosis, central nervous system malformations, platelet dysfunction, and severe failure to thrive. We studied three patients with cholestasis, increased aminotransferases, normal gamma-glutamyl transferase, and developmental and language delay. Whole exome sequencing analysis identified VPS33B variants in all patients: patients 1 and 2 presented a novel homozygous variant at position c.1148T>A. p.(Ile383Asn), and patient 3 was compound heterozygous for the same c.1148T>A. variant, in addition to the c.940-2A>G. variant. ARCS is compatible with the symptomatology presented by the studied patients. However, most patients that have been described in the literature with ARCS had severe failure to thrive and died in the first 6 months of life. The three patients studied here have a mild ARCS phenotype with prolonged survival. Consequently, we believe that the molecular analysis of the VPS33B and VIPAS39 should be considered in patients with normal gamma-glutamyl transferase cholestasis.

Mucopolysaccharidosis VII in Brazil: natural history and clinical findings.

BACKGROUND: Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme ß-glucuronidase, is an ultra-rare disorder with scarce epidemiological data and few publications about natural history and clinical spectrum. METHODS: We conducted a case series report which included retrospective data from all MPS VII patients diagnosed through the "MPS Brazil Network" who were known to be alive in 2020 in Brazil (N = 13). 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: The majority of the patients were from the Northeast region of Brazil. Among the signs and symptoms that raised the clinical suspicion of MPS, coarse face was the most frequent; 58% of the patients had a history of non-immune hydrops fetalis. All the subjects presented short neck and trunk. The majority presented typical phenotypical signs of MPS disorders. They all presented neurodevelopmental delay and cognitive impairment. About half of this cohort had knees deformities. Dysostosis multiplex was identified in almost all patients and cardiomyopathy was less frequent than observed in other types of MPSs. The mean age at diagnosis was 5 years, ranging from 1 to 14 years. Almost all patients (12/13) were homozygous for the c.526C>T (p.Leu176Phe) mutation. A novel variant of the GUSB gene was found, the c.875T>C (p.Leu292Pro), in a compound heterozygous with the c.526C>T (p.Leu176Phe) variant. CONCLUSIONS: This case series is the biggest data collection of MPS VII patients alive in Latin America. The overall clinical picture of the MPS VII patients is very similar to other MPS disorders, including a spectrum of severity and delayed diagnosis.

Multiple sulfatase deficiency: clinical report and description of two novel mutations in a Brazilian patient.

Multiple Sulfatase Deficiency (MSD) is a rare autosomal recessive disease in which the activities of all sulfatases are reduced; its estimated prevalence is 1:1.4 million births. The disease is caused by mutations in SUMF1, which encodes an enzyme involved in the post-translational modification of sulfatases. The MSD phenotype is a combination of the clinical features found in diseases resulting from a deficiency of the individual sulfatases; i.e., mucopolysaccharidosis II, IIIA, IIID, IVA and VI, metachromatic leukodystrophy, X-linked ichthyosis, and the X-linked recessive form of chondrodysplasia punctata. We describe herein the first case of a Brazilian patient with MSD. The case was initially diagnosed as having mucopolysaccharidosis (MPS), due to skeletal alterations, coarse facial features, and urinary excretion of dermatan sulfate and heparan sulfate. Later, after a detailed biochemical investigation, the diagnosis of MSD was established. The analysis of the SUMF1 showed the patient was a compound heterozygote for two novel mutations (p.R349G and p.F244S). This case illustrates the challenges in the diagnosis of a disease considered rare, such as MSD. We point out that the availability of therapy for certain MPS disorders necessitates correct disease assignment, and the need to exclude the likelihood of MSD.

Estimulaçäo ventricular programada em pacientes com cardiopatia chagásica crônica e taquicardia ventricular tratados com amiodaroma ou sotalol / Programmed ventricular stimulation in patients with chronic chagasic cardiomyopathy and ventricular tachycardia treated with amioddarone or sotalol

O objetivo deste estudo foi avaliar o papel da estimulaçao ventricular programada em predizer a eficácia a longo prazo no tratamento de pacientes com cardiopatia chagásica crônica e taquicardia ventricular sustentada (TVS) tratados com amiodarona ou sotalol. Foram estudados 115 pacientes com cardiopatia chagásica crônica e taquicardia ventricular sintomática diagnosticada pelo eletrocardiograma ou Holter, nos quais o estudo eletrofisiológico foi realizado após a impregnaçao com drogas antiarrítmicas da classe III (amiodarona ou sotalol). Foram incluídos pacientes com TVS espontânea, nos quais a estimulaçao ventricular programada foi realizada após o uso das drogas antiarrítmicas da classe III, independentemente da mesma ter sido realizada previamente sem drogas antiarrítmicas. Também foram incluídos os pacientes que apresentaram taquicardia ventricular nao sustentada (TVNS) espontaneamente, nos quais a TVS monomórfica foi induzida sem drogas antiarrítmicas e que, subseqüentemente, foram submetidos a um novo procedimento após o uso das drogas antiarrítmicas da classe III. A estimulaçao ventricular programada, utilizando até 3 extra-estímulos, foi realizada após a impregnaçao com amiodarona (600-1000 mg/dia/7 a 10 dias) ou sotalol (320 mg/dia). De acordo com a resposta à estimulaçao ventricular programada os pacientes foram divididos em 3 grupos: Grupo I - pacientes em que nenhuma TVS foi induzida após a impregnaçao das drogas antiarrítmicas; Grupo II - pacientes com TVS indutível sem colapso hemodinâmico; Grupo III - pacientes com TVS indutível com colapso hemodinâmico. Setenta e oito pacientes apresentaram TVS espontânea (67,8 por cento) e 37 TVNS (32,2 por cento). A média de idade dos pacientes foi de 52ñ10 anos, 69 eram do sexo masculino (60 por cento). Dezenove pacientes (16,5 por cento) apresentavam insuficiência cardíaca avançada (classe funcional 111/IV). A média da fraçao da ejeçao do ventrículo esquerdo foi de 48,6 por cento ñ14 por cento (20 por cento a 80 por cento, mediana de 48 por cento). Trinta e nove pacientes (33,9 por cento) apresentavam fraçao de ejeçao menor que 40 por cento. Vinte e três pacientes (20 por cento) foram incluídos no grupo I, 45 (39 por cento) no grupo II e 47 (41 por cento) no grupo III. As características clínicas basais foram semelhantes nos três grupos, exceto pelo menor número de pacientes do masculino no grupo I...