Reference intervals of spot urine copper excretion in preschool children and potential application in pre-symptomatic screening of Wilson disease

ABSTRACTBackgroundWith spot urine collected from a large control sample of preschool children (aged 3-7 years), reference range of spot urine copper excretion indexes and their biological variation were defined.MethodsIn order to investigate their test performance in screening of Wilson disease in this age group, multiple spot urine samples from 6 WD patients diagnosed at presymptomatic stage were analysed. Cut-off values for spot urine copper concentration, copper to creatinine ratio and copper to osmolality ratio at 0.5 µmol/L, 0.1 µmol/mmol and 0.00085 µmol/mOsmol (32 µg/L, 56 µg/g creatinine and 0.054 µg/mOsmol, respectively, in conventional units) have potential application in differentiation of WD patients.ResultsThe data provides a new insight that the inter-individual variation of spot urine copper indexes (CVg) were moderate with figures around 60% which was similar to other clinically useful urine tests, such as urine albumin excretion ratio. Spot urine copper excretion strongly correlated with both urine creatinine and osmolality. And more than 95% of data points in health preschool children fell within prediction regions by linear regression suggesting a good utility of normalisation by these 2 analytes. Receiver operator curve (ROC) showed that copper to osmolality ratio was the best index with an area under curve (AUC) greater than 0.98.ConclusionsBased on the data, a new WD screening time window targeting preschool children is proposed. Application of a bivariate screening strategy using spot urine copper concentration and urine osmolality may be useful in a population screening program for preschool children.

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PA76 CORRELATION BETWEEN URINARY COPPER EXCRETION AND LIVER COPPER CONTENT WITH AGE IN CHILDREN WITH WILSON DISEASE

Digestive and Liver Disease ◽

10.1016/s1590-8658(10)60670-6 ◽

2010 ◽

Vol 42 ◽

pp. S373

Author(s):

G. Ranucci ◽

E. Nicastro ◽

C. Della Corte ◽

M. Tufano ◽

P. Vajro ◽

...

Keyword(s):

Wilson Disease ◽

Copper Content ◽

Copper Excretion ◽

Liver Copper ◽

Urinary Copper ◽

Urinary Copper Excretion

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Wilson protein expression, copper excretion and sweat production in sweat glands of Wilson disease patients and controls

BMC Gastroenterology ◽

10.1186/1471-230x-8-29 ◽

2008 ◽

Vol 8 (1) ◽

Cited By ~ 8

Author(s):

Mark Schaefer ◽

Mavi Schellenberg ◽

Uta Merle ◽

Karl Heinz Weiss ◽

Wolfgang Stremmel

Keyword(s):

Protein Expression ◽

Wilson Disease ◽

Sweat Glands ◽

Copper Excretion ◽

Sweat Production ◽

Wilson Protein

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PEDIATRIC H1069Q CARRIERS IN WILSON DISEASE PRESENT WITH HIGHER CERULOPLASMIN AND SERUM COPPER CONCENTRATIONS AND LOWER 24H URINARY COPPER EXCRETION

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/00005176-200505000-00208 ◽

2005 ◽

Vol 40 (5) ◽

pp. 683-684

Author(s):

M Dadalski ◽

P Socha ◽

H Schmidt ◽

G Oracz ◽

B Muszynska ◽

...

Keyword(s):

Wilson Disease ◽

Serum Copper ◽

Copper Excretion ◽

Urinary Copper ◽

Urinary Copper Excretion ◽

Disease Present

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PET with 64Cu-Histidine for Noninvasive Diagnosis of Biliary Copper Excretion in Long-Evans Cinnamon Rat Model of Wilson Disease

Journal of Nuclear Medicine ◽

10.2967/jnumed.111.092361 ◽

2012 ◽

Vol 53 (6) ◽

pp. 961-968 ◽

Cited By ~ 10

Author(s):

R. Bahde ◽

S. Kapoor ◽

K. K. Bhargava ◽

M. L. Schilsky ◽

C. J. Palestro ◽

...

Keyword(s):

Rat Model ◽

Wilson Disease ◽

Noninvasive Diagnosis ◽

Copper Excretion ◽

Long Evans

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Long‐term evaluation of urinary copper excretion and non‐caeruloplasmin associated copper in Wilson disease patients under medical treatment

Journal of Inherited Metabolic Disease ◽

10.1002/jimd.12046 ◽

2019 ◽

Vol 42 (2) ◽

pp. 371-380 ◽

Cited By ~ 2

Author(s):

Jan Pfeiffenberger ◽

Christine Marie Lohse ◽

Daniel Gotthardt ◽

Christian Rupp ◽

Markus Weiler ◽

...

Keyword(s):

Medical Treatment ◽

Wilson Disease ◽

Copper Excretion ◽

Urinary Copper ◽

Term Evaluation ◽

Urinary Copper Excretion

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Biochemical markers for the diagnosis and monitoring of Wilson Disease

10.33176/aacb-18-00014 ◽

2019 ◽

Vol 40 (2) ◽

pp. 59-77 ◽

Cited By ~ 12

Keyword(s):

Wilson Disease ◽

Biochemical Markers ◽

Dna Analysis ◽

Clinical Symptoms ◽

Psychiatric Symptoms ◽

Copper Metabolism ◽

Copper Transporter ◽

Copper Excretion ◽

Progressive Liver Disease ◽

Almost All

Wilson disease (WD) is an autosomal recessively-inherited disorder of copper metabolism and characterised by a pathological accumulation of copper. The ATP7B gene encodes for a transmembrane copper transporter essential for biliary copper excretion. Depending on time of diagnosis, severity of disease can vary widely. Almost all patients show evidence of progressive liver disease. Neurological impairments or psychiatric symptoms are common in WD patients not diagnosed during adolescence. WD is a treatable disorder, and early treatment can prevent the development of symptoms in patients diagnosed while still asymptomatic. This is why the early diagnosis of WD is crucial. The diagnosis is based on clinical symptoms, abnormal measures of copper metabolism and DNA analysis. Available treatment includes chelators and zinc salts which increase copper excretion and reduce copper uptake. In severe cases, liver transplantation is indicated and accomplishes a phenotypic correction of the hepatic gene defect. Recently, clinical development of the new copper modulating agent tetrathiomolybdate has started and direct genetic therapies are being tested in animal models. The following review focuses especially on biochemical markers and how they can be utilised in diagnosis and drug monitoring.

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Random ‘spot’ urinary metanephrines compared with 24-h-urinary and plasma results in phaeochromocytomas and paragangliomas

Acta Endocrinologica ◽

10.1530/eje-19-0809 ◽

2020 ◽

Vol 183 (2) ◽

pp. 129-139 ◽

Cited By ~ 1

Author(s):

Emilia Sbardella ◽

Zoe Maunsell ◽

Christine J H May ◽

Michael Tadman ◽

Tim James ◽

...

Keyword(s):

Urine Output ◽

Plasma Concentrations ◽

Correlation Coefficients ◽

Reference Intervals ◽

Spot Urine ◽

Upper Limit ◽

Plasma Metanephrines ◽

Urinary Metanephrines ◽

Urine Specimens

Background In patients with phaeochromocytomas or paragangliomas (PPGLs), 24-h urine collections for metanephrines (uMNs) are cumbersome. Objective To evaluate the diagnostic utility of ratios to creatinine of ‘spot’ uMNs. Methods Concentrations of uMNs and plasma metanephrines (pMNs) were measured by HPLC-mass-spectrometry. We retrospectively compared correlations of 24-h-urine output and ratio to creatinine in historical specimens and prospectively assessed 24-h and contemporaneous spot urines and, where possible, pMNs. Using trimmed log-transformed values, we derived reference intervals based on age and sex for spot urines. We used multiples of upper limit of normal (ULNs) to compare areas under curves (AUCs) for receiver-operator characteristic curves of individual, and sum and product of, components. Results In 3143 24-h-urine specimens on 2416 patients, the correlation coefficients between the ratios and outputs of metanephrine, normetanephrine and 3-methoxytyramine in 24-h urines were 0.983, 0.905 and 0.875, respectively. In 96 patients, the correlations between plasma concentrations, urine output and ratios in spot specimens were similar to those for raw output or ratios in 24-h specimens. Of the 160 patients with PPGLs, the CIs for AUCs for individual metabolites overlapped for all four types of measurement, as did those for the sum of the multiple ULNs although these were slightly higher (AUC for spot urine: 0.838 (0.529–1), plasma: 0.929 (0.874–0.984) and output: 0.858 (0.764–0.952)). Conclusions Ratios of fractionated metanephrines to creatinine in spot urine samples appear to have a similar diagnostic power to other measurements. The ease of spot urine collection may facilitate diagnosis and follow-up of PPGLs through improved patient compliance.

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