Unusual combination of Shwachman-Diamond syndrome and porphyria.

The syndrome shows a wide range of abnormalities and symptoms. The main characteristics of the syndrome are exocrine pancreatic dysfunction, hematologic abnormalities and growth retardation. Only the first two of these are included in the clinical diagnostic criteria.[1] Hematologic abnormalities: neutropenia may be intermittent or persistent and is the most common hematological finding. Low neutrophil counts leave patients at risk of developing severe recurrent infections that may be life-threatening. Anemia (low red blood cell counts) and thrombocytopenia (low platelet counts) may also occur. Bone marrow is typically hypocellular, with maturation arrest in the myeloid lineages that give rise to neutrophils, macrophages, platelets and red blood cells. Patients may also develop progressive marrow failure or transform to acute myelogenous leukemia. Exocrine pancreatic dysfunction: Pancreatic exocrine insufficiency arises due to a lack of acinar cells that produce digestive enzymes. These are extensively depleted and replaced by fat. A lack of pancreatic digestive enzymes leaves patients unable to digest and absorb fat. However, pancreatic status may improve with age in some patients. Growth retardation: More than 50% of patients are below the third percentile for height, and short stature appears to be unrelated to nutritional status. Other skeletal abnormalities include metaphyseal dysostosis (45% of patients), thoracic dystrophy (rib cage abnormalities in 46% of patients) and costochondral thickening (shortened ribs with flared ends in 32% of patients). Skeletal problems are one of the most variable components of SDS, with 50% affected siblings from the same family discordant for clinical presentation or type of abnormality. Despite this, a careful review of radiographs from 15 patients indicated that all of them had at least one skeletal anomaly, though many were subclinical. Other features include metaphysial dysostosis, mild hepatic dysfunction, increased frequency of infections. The article describes an unusual combination of Shwachman-Diamond syndrome and porphyria

INSIDIOUS RECURRENT ABDOMINAL PAIN

Porphyrias are a group of inherited metabolic disorders of heme biosynthesis leading to excessive accumulation and excretion of porphyrins.The variable clinical manifestations may determine a delay in the diagnosis, followed by a possible negative clinical outcome. We describe a case of a 14-year-old girl with ShwachmanDiamond syndrome (SDS) and epilepsy admitted with severe cyclic abdominal pain not responsive to antalgic therapy, localized in the epigastric area, irradiating to the whole abdomen and the back, associated to aspecific symptoms (diarrhea, fever,vomiting). During hospitalization, the girl was asymptomatic. We excluded infectious, autoimmune, endocrinological causes, a relapse of SDS and performed a screening for porphyria that resulted negative. After each attack, she referred presenting urinary retention followed by hyperchromic urines, anxiety and paresthesias. Past clinical data showed hyponatremia, tachycardia and hypertension. Eventually, increased values of ALA (8.21 mg/l) and PBG (3.96 mg/l) were found; exposure of fresh urines to sunlight caused a change of their color. Finally, genetic analysis was negative. These findings allowed the diagnosis of porphyria, therefore we prescribed a normocalorichyperglucidic diet andpreventive glucose solutions in stressing situations, with regression of symptoms. Acute porphyrias present with life-threatening crisis secondary to the injury of central, peripheral and autonomic nervous system. They can be triggered by drugs, alcohol, infections, reduced caloric intake, endogenous hormone cycles and stressing situations. The characteristic manifestations are severe cyclic abdominal pain, neurological or psychiatric symptoms and/or hyponatremia. Diagnostic is the assessment of plasmatic PBG/ALA, always increased during an attack, normal during remission. Treatment is human haemin although, in mild attacks, a diet with high carbohydrates and/or preventive glucose infusions is effective; a negative genetic evaluation should never exclude the diagnosis. It is important considering acute porphyria in the differential diagnosis of severe cyclic abdominal pain, particularly in subjects affected by different and/or rare clinical disorders

A RARE ASSOCIATION: ACUTE DISSEMINATED ENCEPHALOMYELITIS IN CHILD AFFECT BY AUTOIMMUNE HAEMOLYTIC ANAEMIA AND AUTOIMMUNE THROMBOCYTOPENIA

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating illness, characterize-ed by a monophasic course frequently associated with infections or previous immunization. Regarding pathogenesis, encephalomyelitis is associated with some immunological mechanisms. Post-infection or post-vaccination inflammatory reactions in the perivenular region in the central nervous system (CNS) may be explained by a molecular mimicry mechanism. An antecedent infection was identified in 72–77% of paediatric patients. We present a case of a 5 year-old girl in follow up for autoimmune thrombocytopenia (AT) and autoimmune haemolytic anaemia (AHA) in steroid treatment, with history of left hemiparesis, language delay, from as a consequence of perinatal suffering, who has developed ADEM. This patient presented with progressive weakness of limbs, neck pain associated with fever from one day. It was acute in onset and gradually progressive. She became quickly hypotonic and hyporesponsive and had reduced level of consciousness. Within 12 hours of admission, the patient developed sphincter incontinence and dysphagia. After exclusion of papilloedema, lumbar puncture has been performed. An urgent MRI was performed, which showed multiple subcortical lesions of varying size showing hyperintensities in TR at the bridge and in T2 at the medulla . Cerebrospinal fluid (CSF) study showed cell count of 40 cells/mm3 , protein 58 mg/dL, glucose 54 mg/dL. No oligoclonal bands were present in CSF. Blood and CSF cultures were negative like other infectiological analyzes. Also CSFPCR for the presence of bacteria and virus was negative. Her autoimmune profile with antinuclear antibody was also negative. The clinical features and the MRI findings were suggestive of ADEM. Partial quadriplegia, and reduction of reflexes, as seen in the myelitic form of ADEM, were present. She had developed ADEM while on the maintenance dose of prednisolone. After diagnosis, intravenous methylprednisolone was given at 30 mg/kg daily for 5 days. After 48 hours there was a significant improvement in the patient‘s clinical condition. A regimen of oral steroid was advised after intravenous therapy . The patient responded well to steroid therapy. No residual lesion was found on follow-up. AT and AHA are relatively uncommone. There are studies postulating the possibility of a combination of several autoimmune diseases. Very few cases have been found with this rare association in the literature. Follow-up of these patients is essential for detecting the development of other autoimmune disease in such case

Pharmacogenomics of Pediatric Cardiac Arrest: Cisplatin Treatment Worsened by a Ryanodine Receptor 2 Gene Mutation

In thelast few decades, the roles of cardio-oncology and cardiovascular geneticsgained more and more attention in research and daily clinical practice, shaping a new clinical approach and management of patients affected by cancer and cardiovascular disease. Genetic characterization of patients undergoing cancer treatment can support a better cardiovascular risk stratification beyond the typical risk factors, suchas contractile function and QT interval duration, uncovering a possible patient’s concealed predisposition to heart failure, life threatening arrhythmias and sudden death. Specifically, an integrated cardiogenetic approach in daily oncological clinical practice can ensure the best patient-centered healthcare model, suggesting, also the adequate cardiac monitoring timing and alternative cancer treatments, reducing drug-related complications. We report the case of a 14-month-old girl affected by neuroblastoma, treated by cisplatin, complicated by cardiac arrest. We described the genetic characterization of a Ryanodine receptor 2 (RYR2) gene mutation and subsequent pharmacogenomic approach to better shape the cancer treatment

Pharmacogenomics of Pediatric Cardiac Arrest: Cisplatin Treatment Worsened by a Ryanodine Receptor 2 Gene Mutation

In thelast few decades, the roles of cardio-oncology and cardiovascular geneticsgained more and more attention in research and daily clinical practice, shaping a new clinical approach and management of patients affected by cancer and cardiovascular disease. Genetic characterization of patients undergoing cancer treatment can support a better cardiovascular risk stratification beyond the typical risk factors, suchas contractile function and QT interval duration, uncovering a possible patient’s concealed predisposition to heart failure, life threatening arrhythmias and sudden death. Specifically, an integrated cardiogenetic approach in daily oncological clinical practice can ensure the best patient-centered healthcare model, suggesting, also the adequate cardiac monitoring timing and alternative cancer treatments, reducing drug-related complications. We report the case of a 14-month-old girl affected by neuroblastoma, treated by cisplatin, complicated by cardiac arrest. We described the genetic characterization of a Ryanodine receptor 2 (RYR2) gene mutation and subsequent pharmacogenomic approach to better shape the cancer treatment