Genetic analysis of ATP7B in 102 south Indian families with Wilson disease.

Wilson disease (WD) is an autosomal recessive disorder, characterized by excessive deposition of copper in various parts of the body, mainly in the liver and brain. It is caused by mutations in ATP7B. We report here the genetic analysis of 102 WD families from a south Indian population. Thirty-six different ATP7B mutations, including 13 novel ones [p.Ala58fs*19, p.Lys74fs*9, p.Gln281*, p.Pro350fs*12, p.Ser481*, p.Leu735Arg, p.Val752Gly, p.Asn812fs*2, p.Val845Ala, p.His889Pro, p.Ile1184fs*1, p.Val1307Glu and p.Ala1339Pro], were identified in 76/102 families. Interestingly, the mutation analysis of affected individuals in two families identified two different homozygous mutations in each family, and thus each affected individual from these families harbored two mutations in each ATP7B allele. Of 36 mutations, 28 were missense, thus making them the most prevalent mutations identified in the present study. Nonsense, insertion and deletion represented 3/36, 2/36 and 3/36 mutations, respectively. The haplotype analysis suggested founder effects for all the 14 recurrent mutations. Our study thus expands the mutational landscape of ATP7B with a total number of 758 mutations. The mutations identified during the present study will facilitate carrier and pre-symptomatic detection, and prenatal genetic diagnosis in affected families.

Symptomatic Narcolepsy as a Presenting Feature of Neuromyelitis Optica.

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness. It can be either primary or symptomatic due to other neurologic disorders. Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder in which symptomatic narcolepsy is being described as one of the core clinical features. Here, we report a patient with NMO who presented with narcolepsy. Signal changes on magnetic resonance imaging in hypothalamus and other periventricular regions of high aquaporin-4 expression should prompt considering NMO as diagnosis. Serum anti-aquaporin-4 IgG antibody testing should be done in such cases, and appropriate treatment should be initiated to prevent further neurological worsening and relapses.

Intractable vomiting and hiccups as the presenting symptom of neuromyelitis optica.

Vomiting and hiccups can be due to peripheral or central causes. Neurological diseases causing vomiting and hiccups are due to lesions of medulla involving area postrema and nucleus tractus solitarius. Neuromyelitis optica (NMO) is one such disease which involves these structures. However refractory vomiting and hiccups as the presenting symptom of NMO is unusual. Here we report a patient with NMO in whom refractory vomiting and hiccups were the sole manifestation of the first attack. Diagnosis can be missed at this stage leading to delay in treatment and further complications. This case demonstrates the importance of considering NMO in any patient presenting with refractory vomiting and hiccups and with local and metabolic causes ruled out and linear medullary lesion on magnetic resonance imaging may indicate the diagnosis even when the classical clinical criteria are not met. Anti NMO antibody testing should be done and if positive appropriate treatment should be initiated to prevent further neurological damage.