A critical evaluation of copper metabolism in indian wilson’s disease children with special reference to their phenotypes and relatives

Prasad, Rajendra; Kaur, Gurjit; Walia, B. N. S.

doi:10.1007/bf02784267

Cited by 18 publications

(9 citation statements)

References 15 publications

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“…In a study of copper metabolism in WD in north India, ceruloplasmin levels were significantly lower in patient population when compared to controls and there was a good co-relation between non-ceruloplasmin bound copper and 24-h urinary copper excretion. [46] Analysis of biochemical data in our patients in whom all the three parameters of copper metabolism (serum copper, ceruloplasmin and 24-h urinary copper) were available, revealed low serum ceruloplasmin in 88%, and increased 24-h urinary copper in 96% patients. When a combination either low ceruloplasmin or increased 24-h urinary copper was used, all but one of the 221 patients had abnormality (unpublished data).…”

Section: Biochemicalmentioning

confidence: 98%

Wilson′s disease: An Indian perspective

2009

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Wilson's disease (WD) is an autosomal recessive disease involving a defect of copper transport by the hepatic lysosomes. It leads to excess copper deposition in the liver, the brain, the kidneys and the skeletal system, affecting most commonly children or young adults and running an invariably fatal course if not adequately treated by de-coppering therapy. The last century has witnessed several changes, notable among these are: Increased awareness, improved diagnostic facilities leading to earlier recognition even in the pre-symptomatic phase, clear distinction from its mimics, aggressive therapeutic approaches owing to availability of effective treatment and an overall reduction in the morbidity and mortality. It is widely acknowledged that the disease is not as rare as once believed. Sir SAK Wilson published his landmark article in 1912, but it was only in 1968 that the first patient of WD was reported from our country. Publications from India on WD have focused on phenotypic characterization, documentations of lesser recognized aspects of the disease e.g. seizures, behavior abnormality, speech and cognitive impairment, sub-clinical affection of visual pathway, heart and autonomic function and pre-symptomatic detection. Attempts have been made to understand the clinical heterogeneity of the disease through identification of biochemical and immunological markers, magnetic resonance imaging, neuropathological study and genetic analysis for novel and/or known mutations. Assessment of impairment and severity and effect of various therapeutic interventions namely zinc sulphate on the long-term outcome and quality of life have also been studied. Nevertheless, clinicians often face difficulties in long-term care of these patients. Diagnostic errors leading to delay in diagnosis and initiation of treatment are common, even in patients with positive family history. There is no consensus regarding therapeutic protocols since the use of penicillamine, once a 'gold standard' for treatment, has been debated by experts. Mortality and morbidity of this potentially treatable disease and nonavailability of medications to the poor patients remain a major area of concern.

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Section: Biochemicalmentioning

confidence: 98%

Wilson′s disease: An Indian perspective

2009

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“…Serum ceruloplasmin activity was measured as copper oxidase using p-phenylenediamine dihydrochloride as substrate. Serum copper and 24-hour urine copper were estimated using atomic absorption spectrophotometer as described previously (Kumar et al, 2005;Prasad, Kaur, & Walia, 1998). Presence of KF rings was evaluated by ophthalmologists.…”

Section: Subjects and Sample Collectionmentioning

confidence: 99%

Characterization of mutation spectrum and identification of novel mutations in ATP7B gene from a cohort of Wilson disease patients: Functional and therapeutic implications

Kumari

Kumar

Thapa³

et al. 2018

Human Mutation

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Wilson disease (WD), a copper metabolism disorder, occurs due to the presence of mutations in the gene encoding ATP7B, a protein that primarily facilitates hepatic copper excretion. A better understanding of spectrum and functional significance of ATP7B variants is critical to formulating targeted and personalized therapies. Henceforth, we screened and sequenced 21 exons of ATP7B gene from 50 WD patients and 60 healthy subjects. We identified 28 variants comprising, seven novels in 20% alleles, while eight variations affecting 23% alleles were first time reported in Indian cohort. The c.813C>A, p.(Cys271*) (10%) was the most frequent mutation. Bioinformatics analysis revealed five of seven novel variants viz. c.1600C>A, p.(Pro534Thr); c.1616C>A, p.(Pro539His); c.1924G>T, p.(Asp642Tyr); c.2168G>C, p.(Arg723Thr); c.2174G>C, p.(Arg725Thr) resulted in protein misfolding. Sequence conservation analysis of ATP7B regions containing novel variants documented an evolutionarily conserved nature. Functional analysis of these novel variants in five different cell lines lacking inherent ATP7B expression demonstrated sensitivity to CuCl -treatment, experiencing augmented cellular copper retention and decreased copper excretion as well as ceruloplasmin secretion to that of wildtype-ATP7B expressing cells. Interestingly, pharmacological chaperone 4-phenylbutyrate, a clinically approved compound, partially restored protein function of ATP7B mutants. These findings might enable novel treatment strategies in WD by clinically enhancing the protein expression of mutant ATP7B with residual copper export activity.

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“…Forty‐three patients residing in the states (Punjab, Haryana, Jammu and Kashmir, Western UP, and Chandigarh) of North‐West India were included for mutation analysis. The diagnosis of WD was made on the basis of clinical symptomatology and various biochemical tests as described previously (4). Mutation analysis of ATP7B was performed as described by Thomas et al (3) and Gabor et al (5) with minor modifications.…”

Section: Mutations In Wilson Disease (Wd) Genementioning

confidence: 99%