Post-mortem diagnosis of Pompe disease by exome sequencing in a Moroccan family: a case report.

BACKGROUND: Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy. Its prevalence ranges between 1/9000 and 1/40,000. It is caused by compound heterozygous or homozygous mutations in the GAA gene, which encodes for the lysosomal enzyme alpha-glucosidase, required for the degrading of lysosomal glycogen. CASE PRESENTATION: In this study, we report the case of a Moroccan consanguineous family with hypertrophic cardiomyopathy and sudden cardiac deaths at an early age; our patient was a 7-month-old Moroccan girl. Whole exome sequencing identified the deleterious homozygous mutation c.236_246delCCACACAGTGC (p.Pro79ArgfsX13) of GAA gene leading to a post-mortem diagnosis of Pompe disease. CONCLUSION: The identification of the genetic substrate in our patient, the daughter, confirmed the clinical diagnosis of Pompe disease and allowed us to provide appropriate genetic counseling to the family for future pregnancies.

Exome sequencing identifies primary carnitine deficiency in a family with cardiomyopathy and sudden death.

Pediatric cardiomyopathy is a rare but severe disease with high morbidity and mortality. The causes are poorly understood and can only be established in one-third of cases. Recent advances in genetic technologies, specifically next-generation sequencing, now allow for the detection of genetic causes of cardiomyopathy in a systematic and unbiased manner. This is particularly important given the large clinical variability among pediatric cardiomyopathy patients and the large number of genes (>100) implicated in the disorder. We report on the performance of whole-exome sequencing in members of a consanguineous family with a history of pediatric hypertrophic cardiomyopathy and sudden cardiac death, which led to the identification of a homozygous stop variant in the SLC22A5 gene, implicated in primary carnitine deficiency, as the likely genetic cause. Targeted carnitine tandem mass spectrometry analysis in the patient revealed complete absence of plasma-free carnitine and only trace levels of total carnitine, further supporting the causality of the SLC22A5 variant. l-carnitine supplementation in the proband led to a rapid and marked clinical improvement. This case illustrates the use of exome sequencing as a systematic and unbiased diagnostic tool in pediatric cardiomyopathy, providing an efficient route to the identification of the underlying cause, which lead to appropriate treatment and prevention of premature death.

The Boy from Fez: A tale of five charities, and the global community, joining hands.

A case study in global cooperation between multiple charities and cardiac centers helped to save a 8-year-old Moroccan boy suffering a case of Laubry-Pezzi syndrome with severe aortic regurgitation and ventricular septal defect. His recuperation was aided by the support of communities in both Morocco and Qatar.

Congenital rubella syndrome burden in Morocco: a rapid retrospective assessment.

BACKGROUND: WHO recommends that countries considering introduction of rubella vaccine into their immunisation programme assess their burden of congenital rubella syndrome, to determine whether vaccination is warranted. However, few guidelines exist for such assessments in developing countries. We retrospectively estimated the burden of congenital rubella syndrome in Morocco, and assessed our methods of rapid case finding. METHODS: We undertook case finding in the two cities with Morocco's main tertiary care referral centres, using medical records from births between Jan 1, 1990, and May 31, 2002, disability records from 1965 to 1997, and retinal examinations from deaf students born between 1985 and 1994, applying the WHO definition for a clinically confirmed case of congenital rubella syndrome. We also reviewed disability data for evidence of epidemic periodicity and estimated yearly incidence of the syndrome from congenital cataract data for births between 1990 and 2001. FINDINGS: We identified 62 clinically confirmed cases of congenital rubella syndrome from medical records, 148 from disability records, and 15 in deaf students. We noted no epidemic periodicity in disability data, and estimated a yearly incidence of the syndrome in Morocco of 8.1-12.7 cases per 100000 livebirths. INTERPRETATION: We show evidence of congenital rubella syndrome in Morocco and support the addition of rubella vaccination to the national programme. Various data sources can be explored to rapidly assess burden of the syndrome; ophthalmology departments and outpatient cardiology clinics could offer the most potential for such case finding, dependent on documentation practices.