Browsing by Author "Antunes, D."
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- Hyperprolinemia as a clue in the diagnosis of a patient with a psychiatric disorderPublication . Duarte, M.; Moreira, A.; Antunes, D.; Ferreira, Cristina; Correia, Hildeberto; Sequeira, S.; Marques, M.Background: Over the last few years, microdeletions of the 22q11.2 region responsible for DiGeorge syndrome, or velocardiofacial syndrome, have been increasingly related to neuropsychiatric disorders including schizophrenia and bipolar disorders. These signs seem to be related to certain genes located in the hemideleted region as the proline dehydrogenase (PRODH) and the catecholo-methyltransferase (COMT) genes. The PRODH or proline oxidase deficiency is responsible for hyperprolinemia type 1 (HPI) also causing psychiatric manifestations. Case Report: We describe a 17 year old boy with previous mild psychomotor and speech delay, mild cognitive impairment, and obsessive behaviours who started his adolescent psychiatric care presenting irritablemood and aggressive behaviour with schizophrenia symptoms that scored a “severely ill” level PANSS assessment. Symptoms got worse when he was treated with valproic acid and plasma aminoacids showing increase in alanine and proline, suggested a mitochondrial involvement of the proline metabolic pathway. Results: Mild dysmorphia suggested a possible 22q11.2 deletion genetically confirmed involving both the PRODH and COMT regions. HPI that can present with psychiatric features is however a recessive disorder and therefore the symptoms could not be solely explained by this genetic deletion. Additional investigations also showed disclosed a p.L289m (c.1865 T > A) mutation in the PRODH gene. Discussion: We believe that the association of this mutation together with the 22q11.2 deletion would lead to a decrease of functional protein. Although it may be difficult to diagnosis chromosomal abnormalities in patients with no clear malformations and mild dysmorphic features as in this patient we emphasize need to investigate the aetiology in patients with psychiatric symptoms, especially if they have other systemic manifestations such as developmental delay or psychotic symptoms, as it may be important in the management of the patients.
- Hypomelanosis of Ito vs Pigmentary Mosaicism: a challenging diagnosisPublication . Antunes, D.; Kay, T.; Cabete, J.; Marques, B.; Brito, F.; Correia, H.; Nunes, L.Introdution: Since 1952 several case reports and case series of Hypomelanosis of Ito (HI) has described different associations with multiple extra cutaneous manifestations, being the neurological anomalies the most frequent and important ones. Methods: We report a 5-years-old girl, refered by dyschromia , minor dysmorphic features, strabism, ventricular septal heart defect and slight learning difficulties. The peripheral blood karyotype that was normal. Hypopigmented patches along Blaschko’s lines were observed. Other anomalies included a simian palm crease on right hand, persistency of fetal pads, and mild genu valgum/recurvatum. A skin biopsy for histopathological and cytogenetic studies was performed on a hypopigmented patch and a magnetic resonance imaging (MRI) of central nervous system (CNS) was requested. Results: Histopathological study of the skin was inconclusive. However, the cytogenetic study revealed the presence of mosaicism: one normal cell line and one abnormal cell line with monosomy of chromosome 18 and presence of a marker chromosome (46,XX,-18,+mar[22]/46,XX[28]) . Fluorescence in situ hybridization (FISH) technique identified the marker as a derivative of chromosome 18, comprising the centromeric region and a small portion of euchromatic material. CNS MRI was normal. Discussion: Some authors suggest that HI would be better designated as “pigmentary mosaicism”, following the hypothesis that the chromosomal abnormalities reported specifically disrupt pigmentary genes. Although numerous cases of mosaicism concerning chromosome 18 were previously described, this specific cytogenetic anomaly was not yet reported. The mild phenotype presented in this case suggests that mosaicism may have a low expression. Nevertheless, the loss genetic material in the abnormal cell line raises several questions about future outcomes, especially regarding the theoretical concern of a predisposition to certain malignancies and the difficulty of genetic counseling. This case illustrates the challenge of a diagnosis when facing a variety of phenotypes and reinforces the importance of karyotyping other tissues besides peripheral blood.