A novel presentation of an ATP1A3 gene mutation - case report and literature review.

OBJECTIVE: Mutations in the ATP1A3 gene cause the classical disorders of rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC) and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). However, intermediate phenotypes have also been described, making the range of clinical manifestations associated with mutations in the ATP1A3 gene wider. A rare case of an ATP1A3 gene mutation is presented. CASE REPORT: Genetic testing was performed in a neonate who presented with neurological abnormalities on day 2 of life, severe electrolytic disturbances a few days later and developmental delay and epilepsy a few months later. A pathogenic heterozygous missense mutation in the ATP1A3 gene (c.2482G>A, E828K(p.Glu828Lys) was detected on clinical exome sequencing. CONCLUSIONS: The present case report extends the already described phenotypic variation observed in individuals with ATP1A3 gene mutations. It also illustrates the importance of genetic testing in the case of complex and not straightforward clinical scenarios, particularly when present from a very young age, before clinical criteria for known diagnoses are met.

Delayed presentation of seropositivity in pre-existent coeliac disease in patients with Type 1 diabetes mellitus: a possible co-occurrence?

OBJECTIVE: The co-occurrence of coeliac disease (CD) and type 1 diabetes mellitus (T1DM) is well described and is mainly explained by sharing of common pathogenic mechanisms, such as common high-risk human lymphocyte antigen (HLA) genotypes (DR-DQ). PATIENTS AND METHODS: We describe a 12-year-old female patient with T1DM who presented with prolonged and severe glucose dysregulation. Extensive investigations, including coeliac screen, were negative. RESULTS: 3 years after glucose dysregulation manifested, coeliac screen testing was positive and coeliac disease was confirmed with bowel biopsy. Compliance to a gluten-free diet resulted in improvement of glucose control and seronegativity 9 months post-diagnosis. CONCLUSIONS: This is the first case report describing delayed seropositivity of CD and suggests that CD enteropathy may precede positive serology and could cause severe glucose dysregulation in patients with T1DM.