RESUMO
Distal 15q25.2 microdeletions have recently been reported as a copy number variation (CNV) locus for neurodevelopmental and neuropsychiatric disorders with variable outcome. In addition, more proximal microdeletions of 15q25.2 have been described as a susceptibility locus for cognitive deficits, congenital diaphragmatic hernia (CDH), and Diamond-Blackfan anaemia (DBA). We describe two patients with 15q25.2 deletion, one with the more distal deletion and the other with a deletion overlapping both the distal and proximal 15q25.2 deletions and compare them to the 18 so far reported patients with 15q25.2 deletions. We provide a characterization of the 15q25.2 microdeletions and contribute to the genotype-phenotype delineation for these two novel microdeletion syndromes.
Assuntos
Loci Gênicos , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/fisiopatologia , Anemia de Diamond-Blackfan/genética , Anemia de Diamond-Blackfan/fisiopatologia , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 15/genética , Deleção de Genes , Estudos de Associação Genética , Genótipo , Alemanha , Hérnia Diafragmática/genética , Hérnia Diafragmática/fisiopatologia , Hérnias Diafragmáticas Congênitas , Humanos , Hibridização in Situ Fluorescente , Masculino , Análise em Microsséries , FenótipoRESUMO
AIM: A 6-month-old infant with severe hyporegenerative anaemia, muscular hypotonia and developmental delay is reported, and the metabolic, diagnostic and therapeutic implications of this case are discussed. RESULTS: Diagnostic work-up disclosed vitamin B12 depletion with an elevated excretion of methylmalonic acid (MMA), but a normal plasma total homocysteine. MRI showed fronto-temporal atrophy and a delay in myelinization. The boy's disease was attributable to a maternal atrophic gastritis. After initiation of vitamin B12 supplementation, he quickly recovered regarding haematopoiesis and MMA excretion. His neurological development completely normalized during 18 months of follow-up including assessment by Bayley scores. CONCLUSION: As the majority of reported patients with this acquired form of methylmalonic aciduria show a persistent neurological deficit, early diagnosis of this condition is mandatory and should include sensitive markers of vitamin B12 depletion, namely MMA formation and plasma homocysteine.