Pulmonary Hypertension Associated With Scurvy and Vitamin Deficiencies in an Autistic Child

Duvall, Melody G.; Pikman, Yana; Kantor, David; Ariagno, Katelyn; Summers, Lisa; Sectish, Theodore C.; Mullen, Mary P.

doi:10.1542/peds.2012-3054

Cited by 53 publications

(65 citation statements)

References 11 publications

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“…Furthermore, thiamine deficiency resulting in cardiovascular beriberi has also been reported as a rare reversible cause of PH [48]. PH associated with vitamin C deficiency in the setting of pulmonary complications has been documented in several patients [49–50]. PH in these patients may be a result of reduced synthesis of nitric oxide, a potent mediator of vascular muscle relaxation.…”

Section: Resultsmentioning

confidence: 99%

Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension

Ong

Mullen

Austin

et al. 2017

Circulation Research

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Rationale Pediatric pulmonary hypertension (PH) is a heterogeneous condition with varying natural history and therapeutic response. Precise classification of PH subtypes is therefore crucial for individualizing care. However, gaps remain in our understanding of the spectrum of PH in children. Objective We seek to study the manifestations of PH in children, and to assess the feasibility of applying a network-based approach to discern disease subtypes from comorbidity data recorded in longitudinal datasets. Methods and Results A retrospective cohort study comprising 6,943,263 children (<18 years of age) enrolled in a commercial health insurance plan in the US, between January 2010 and May 2013. A total of 1,583 (0.02%) children met the criteria for PH. We identified comorbidities significantly associated with PH compared with the general population of children without PH. A Bayesian comorbidity network was constructed to model the interdependencies of these comorbidities, and network clustering analysis was applied to derive disease subtypes comprising subgraphs of highly connected comorbid conditions. A total of 186 comorbidities were found to be significantly associated with PH. Network analysis of comorbidity patterns captured most of the major PH subtypes with known etiological basis defined by the World Health Organization and Panama classifications. The analysis further identified a number of subtypes documented in only a few case studies, including rare subtypes associated with several well-described genetic syndromes. Conclusions Application of network science to model comorbidity patterns recorded in longitudinal datasets can facilitate the discovery of disease subtypes. Our analysis relearned established subtypes, thus validating the approach, and identified rare subtypes that are difficult to discern through clinical observations, providing impetus for deeper investigation of the disease subtypes that will enrich current disease classifications.

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Section: Resultsmentioning

confidence: 99%

Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension

Ong

Mullen

Austin

et al. 2017

Circulation Research

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“…In humans this is exemplified by scurvy, in which ascorbate deficiency causes defective collagen formation by inhibiting one such enzyme, the collagen prolyl hydroxylase, leading to the characteristic signs of poor wound healing, bleeding gums, and widespread hemorrhages (Smith and Talbot 2010). According to multiple case reports, some patients with scurvy also develop severe pulmonary hypertension that rapidly resolves upon treatment with ascorbate, and that could in theory derive from inhibition of HIF hydroxylase enzymes (Mehta et al 1996;Nagamatsu et al 2009;Mertens and Gertner 2011;Kupari and Rapola 2012;Duvall et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Contrasting effects of ascorbate and iron on the pulmonary vascular response to hypoxia in humans

et al. 2014

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Hypoxia causes an increase in pulmonary artery pressure. Gene expression controlled by the hypoxia‐inducible factor (HIF) family of transcription factors plays an important role in the underlying pulmonary vascular responses. The hydroxylase enzymes that regulate HIF are highly sensitive to varying iron availability, and iron status modifies the pulmonary vascular response to hypoxia, possibly through its effects on HIF. Ascorbate (vitamin C) affects HIF hydroxylation in a similar manner to iron and may therefore have similar pulmonary effects. This study investigated the possible contribution of ascorbate availability to hypoxic pulmonary vasoconstriction in humans. Seven healthy volunteers undertook a randomized, controlled, double‐blind, crossover protocol which studied the effects of high‐dose intravenous ascorbic acid (total 6 g) on the pulmonary vascular response to 5 h of sustained hypoxia. Systolic pulmonary artery pressure (SPAP) was assessed during hypoxia by Doppler echocardiography. Results were compared with corresponding data from a similar study investigating the effect of intravenous iron, in which SPAP was measured in seven healthy volunteers during 8 h of sustained hypoxia. Consistent with other studies, iron supplementation profoundly inhibited hypoxic pulmonary vasoconstriction (P < 0.001). In contrast, supraphysiological supplementation of ascorbate did not affect the increase in pulmonary artery pressure induced by several hours of hypoxia (P = 0.61). We conclude that ascorbate does not interact with hypoxia and the pulmonary circulation in the same manner as iron. Whether the effects of iron are HIF‐mediated remains unknown, and the extent to which ascorbate contributes to HIF hydroxylation in vivo is also unclear.

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“…17 Vitamin C deficiency may occur concurrently with other nutritional deficiencies such as thiamine (vitamin B1), pyridoxine (vitamin B6), cobalamin (vitamin B12), and vitamin D and this should be kept in mind while investigating scurvy. 30 A nanoprobe for detection and imaging of ascorbic acid in living cells and in vivo based on the specific reaction of cobalt oxyhydroxide and ascorbic acid has been proposed and currently experimentally investigated. 41 The plain radiological findings in scurvy are already been described above.…”

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confidence: 99%

Scurvy in pediatric age group – A disease often forgotten?

Agarwal

Shaharyar

Kumar

et al. 2015

Journal of Clinical Orthopaedics and Trauma

131

163

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Vitamin C Scurvy ChildrenPediatric age group a b s t r a c t Scurvy is caused by prolonged severe dietary deficiency of vitamin C. Being rare as compared to other nutritional deficiencies, it is seldom suspected and this frequently leads to delayed recognition of this disorder. Children with abnormal dietary habits, mental illness or physical disabilities are prone to develop this disease. The disease spectrum of scurvy is quite varied and includes dermatological, dental, bone and systemic manifestations. Subperiosteal hematoma, ring epiphysis, metaphyseal white line and rarefaction zone along with epiphyseal slips are common radiological findings. High index of suspicion, detailed history and bilateral limb radiographs aids physician in diagnosing this eternal masquerader. We searched Pubmed for recent literature (2009e2014) with search terms "scurvy" "vitamin C deficiency" "ascorbic acid deficiency" "scurvy and children" "scurvy and pediatric age group". There were a total of 36 articles relevant to pediatric scurvy in children (7 reviews and 29 case reports) which were retrieved. The review briefly recapitulates the role of vitamin C, the various disease manifestations and the treatment of scurvy to create awareness of the disease which still is reported from our country, although sporadically. The recent advances related to scurvy and its management in pediatric age group are also incorporated.

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Pulmonary Hypertension Associated With Scurvy and Vitamin Deficiencies in an Autistic Child

Cited by 53 publications

References 11 publications

Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension

Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension

Contrasting effects of ascorbate and iron on the pulmonary vascular response to hypoxia in humans

Scurvy in pediatric age group – A disease often forgotten?

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