Case report: Variability in clinical features as a potential pitfall for the diagnosis of Barth syndrome.

Background: Barth syndrome is a rare genetic disease characterized by cardiomyopathy, skeletal muscle weakness, neutropenia, growth retardation and organic aciduria. This variable phenotype is caused by pathogenic hemizygous variants of the TAFAZZIN gene on the X chromosome, which impair metabolism of the mitochondrial phospholipid cardiolipin. Although most patients are usually diagnosed in the first years of life, the extremely variable clinical picture and the wide range of clinical presentations may both delay diagnosis. This is the case reported here of a man affected with severe neutropenia, who was not diagnosed with Barth syndrome until adulthood. Case presentation: We describe herein a family case, specifically two Caucasian male cousins sharing the same mutation in the TAFAZZIN gene with a wide phenotypic variability: an infant who was early diagnosed with Barth syndrome due to heart failure, and his maternal cousin with milder and extremely different clinical features who has received the same diagnosis only at 33 years of age. Conclusions: Our report supports the underestimation of the prevalence of Barth syndrome, which should be always considered in the differential diagnosis of male patients with recurrent neutropenia with or without signs and symptoms of cardiomyopathy.

GAU-PED study for early diagnosis of Gaucher disease in children with splenomegaly and cytopenia.

BACKGROUND: Gaucher disease (GD) diagnosis can be delayed due to non-specific symptoms and lack of awareness, leading to unnecessary procedures and irreversible complications. GAU-PED study aims to assess GD prevalence in a high-risk pediatric population and the presence, if any, of novel clinical or biochemical markers associated with GD. MATERIALS AND METHODS: DBS samples were collected and tested for ß-glucocerebrosidase enzyme activity for 154 patients selected through the algorithm proposed by Di Rocco et al. Patients showing ß-glucocerebrosidase activity below normal values were recalled to confirm the enzyme deficiency with the gold standard essay on cellular homogenate. Patients tested positive at the gold standard analysis were evaluated through GBA1 gene sequencing. RESULTS: 14 out of 154 patients were diagnosed with GD, with a prevalence of 9.09% (5.06-14.78%, CI 95%). Hepatomegaly, thrombocytopenia, anemia, growth delay/deceleration, elevated serum ferritin, elevated Lyso-Gb1 and chitotriosidase were significantly associated with GD. CONCLUSIONS: GD prevalence in a pediatric population at high-risk appeared to be higher compared to high-risk adults. Lyso-Gb1 was associated with GD diagnosis. The algorithm proposed by Di Rocco et al. can potentially improve the diagnostic accuracy of pediatric GD, allowing the prompt start of therapy, aiming to reduce irreversible complications.

Expanding the clinical and neuroimaging features of post-varicella arteriopathy of childhood.

OBJECTIVE: Post-varicella arterial ischemic stroke (AIS) is considered an uncommon cause of pediatric stroke that is considered a self-limiting, monophasic disease. However, in a subset of patients, disease recurs; the prevalence of vasculopathy or AIS recurrence, severity of clinical outcomes, and standardized therapies have not been well characterized. Herein, we determined the clinical-neuroradiological features, long-term evolution, and relationship between acute phase treatment and vasculopathy recurrence in a pediatric population with post-varicella AIS. METHODS: Clinical, laboratory, and neuroradiological features of 22 children with post-varicella AIS between 2010 and 2019 (16 males, mean age at stroke 4 years, range 1.7-10) were reviewed. Statistical analyses were performed using χ2 and Fisher exact tests. RESULTS: Of the 22 cases, mean time from varicella to stroke was 4.5 months with 3 cases presenting more than 12 months after rash; 21 (95%) were not vaccinated for varicella; 3 (13.6%) had posterior circulation involvement; and 5 (22.7%) had AIS or vasculopathy recurrence, of which 4 recurred 6.1 months to 2.8 years after initial clinical onset. Recurrence was associated with lack of antiviral treatment during the first episode (p = 0.02). CONCLUSIONS: Post-varicella AIS can occur months after rash making diagnosis challenging. Because recurrent vasculopathy was seen predominantly in cases not treated with antiviral therapy during initial presentation, it is important to rapidly diagnose post-varicella AIS through clinical criteria and/or virological testing then treat with antivirals to prevent recurrence.

Intrathecal nusinersen treatment for SMA in a dedicated neuromuscular clinic: an example of multidisciplinary and integrated care.

Nusinsersen is now available in Italy for all SMA types. We describe the experience with intrathecal treatment with nusinersen in 50 patients with SMA at the NEMO Center (NEuroMuscular Omniservice Clinical Center) in Milan, a neuromuscular patient-centered clinic hosted within Niguarda Hospital, a National Public General Hospital. Our results indicate that the pathway of care described outweighs the burden due to the repeated intrathecal injections. Irrespective of age and severity, the treatment is feasible, accessible, and replicable provided that there is a multidisciplinary team having experience and training in SMA.