Síndrome H: primer caso pediátrico reportado en América Latina

Barriga, Hugo Hernán Abarca; Trubnykova, Milana; Córdoba, Victoria Polar; Diaz, Katherine Joyce Ramos; Alfaro, Nélida Aviles

doi:10.1016/j.rchipe.2016.03.006

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…The c.1087 > T (p.R363W) mutation in patient 1 has been described twice before in patients of Hispanic background, both with H syndrome. Similar to patient 1, both of these patients are homozygous for this mutation [ 23 , 24 ]. The c.347 T > G (p.M116R) mutation in patients 1 and 2 was reported once before in a Caucasian American patient with Pigmented Hypertrophic Dermatosis with IDDM [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

H syndrome: 5 new cases from the United States with novel features and responses to therapy

et al. 2017

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BackgroundH Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). Less than 100 patients with H syndrome have been described in the literature, with the majority being of Arab descent, and only a few from North America.Case presentationHere we report five pediatric patients from three medical centers in the United States who were identified to have H syndrome by whole exome sequencing. These five patients, all of whom presented to pediatric rheumatologists prior to diagnosis, include two of Northern European descent, bringing the total number of Caucasian patients described to three. The patients share many of the characteristics previously reported with H syndrome, including hyperpigmentation, hypertrichosis, short stature, insulin-dependent diabetes, arthritis and systemic inflammation, as well as some novel features, including selective IgG subclass deficiency and autoimmune hepatitis. They share genetic mutations previously described in patients of the same ethnic background, as well as a novel mutation. In two patients, treatment with prednisone improved inflammation, however both patients flared once prednisone was tapered. In one of these patients, treatment with tocilizumab alone resulted in marked improvement in systemic inflammation and growth. The other had partial response to prednisone, azathioprine, and TNF inhibition; thus, his anti-TNF biologic was recently switched to tocilizumab due to persistent polyarthritis. Another patient improved on Methotrexate, with further improvement after the addition of tocilizumab.ConclusionH syndrome is a rare autoinflammatory syndrome with pleiotropic manifestations that affect multiple organ systems and is often mistaken for other conditions. Rheumatologists should be aware of this syndrome and its association with arthritis. It should be considered in patients with short stature and systemic inflammation, particularly with cutaneous findings. Some patients respond to treatment with biologics alone or in combination with other immune suppressants; in particular, treatment of systemic inflammation with IL-6 blockade appears to be promising. Overall, better identification and understanding of the pathophysiology may help devise earlier diagnosis and better treatment strategies.

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Section: Discussionmentioning

confidence: 99%

H syndrome: 5 new cases from the United States with novel features and responses to therapy

et al. 2017

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“…After detecting a mutation in the SCL29A3 gene (NM_018344.6:c.971C > T; (p.Pro324Leu)), described as pathological [ 4 , 13 ] in the gene panel ordered for SNHL, the patient was diagnosed with HS, which was compatible with his phenotype. Later on, because early-onset IDDM is a typical feature of HS [ 3 , 6 , 12 ], a genetic panel was done to his sister and the same mutation was found.…”

Section: Case Presentationmentioning

confidence: 99%

“…Since then, around 100 cases have been reported [ 3 – 5 ]. The average age at onset is 9.7 years [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia

et al. 2021

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Background H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. Case presentation 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. Conclusions We report the most severe disease course produced by HS described so far in the literature. Our patient’s manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.

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“…These microduplications correlated to Laurin–Sandrow syndrome and Haas‐type polysyndactyly, according to the ZRS region length (Lohan et al, ). Moreover, Peruvian geneticists of INSN described unique cases of pterygium‐digital keloid dysplasia (Abarca et al, ), H syndrome (Abarca Barriga, Trubnykova, Polar Córdoba, Ramos Diaz, & Aviles, ), van der Knaap syndrome (Hamilton et al, ), and Shawaf‐Traboulsi syndrome (Abarca Barriga et al, ). Last, international collaboration permitted reports of two common genetic syndromes—that is, Noonan (Kruszka et al, ) and Williams‐Beuren (Kruszka et al, )—with clinical geneticists of the National Human Genome Research Institute of The National Institutes of Health; and with other geneticists of different sites in the globe, contributing to the worldwide clinical genetics area.…”

Section: Healthcare Services Of Genetics and Genomicsmentioning

confidence: 99%

Genetics and genomics in Peru: Clinical and research perspective

Guio

Poterico

Levano³

et al. 2018

Molec Gen & Gen Med

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Síndrome H: primer caso pediátrico reportado en América Latina

Abstract: These findings are consistent with H syndrome, and this is the first reported case in Latin America. The key to the diagnosis is the finding of hyperpigmentation with hypertrichosis.

Cited by 7 publications

References 18 publications

H syndrome: 5 new cases from the United States with novel features and responses to therapy

H syndrome: 5 new cases from the United States with novel features and responses to therapy

Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia

Genetics and genomics in Peru: Clinical and research perspective

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