The long-term treatment of a patient with type 1 diabetes mellitus and glutaric aciduria type 1: the effect of insulin.

UNLABELLED: The coexistence of two diseases associated with different metabolic disorders is a very rare event. Some associations, although sporadic, can be particularly challenging both in terms of diagnostic and therapeutic management and in terms of theoretical perspective. Here, we report a child affected by type 1 diabetes mellitus (T1DM) and glutaric aciduria type 1 (GA1). The child was diagnosed with classical T1DM at 15 months of age, with a tendency toward hypoglycemia. A few months later, during an acute intercurrent infective episode, the child displayed acute hypotonia of the lower limbs and limbs dystonia. A brain MRI showed bilateral striatal necrosis, suggesting GA1 diagnosis. Treatment with a low-lysine dietary regimen and carnitine supplementation was started and resulted in an improvement in metabolic control and a reduction of hypoglycemic episodes along with an increasing in insulin daily dose. After 2 years, the neurological outcome consisted of a reduction in dystonic movements and a metabolic stability of both diseases. CONCLUSION: This case provides some insight into the reciprocal interconnections between the two metabolic disorders. Similar pathogenic mechanisms responsible for the neuronal injury might have impacted each other, and a strict relationship between a specific aspect of GA1-impaired metabolism and glucose homeostasis might explain how the tailored management of GA1 was not only effective in controlling the disease, but it also resulted in an improvement in the control of the glycemic profile. What in known: • Glutaric aciduria type 1 (GA1) usually presents in childhood with severe and possibly irreversible neuronal damage, triggered by a catabolic stress • The association of GA1 with other diseases, including type 1 diabetes mellitus (T1DM), is a rare event, complicating the treatment management What is new: • Insulin treatment has a role in preventing GA1 metabolic decompensation, even in the catabolic condition of hypoglycemia • Promoting GA1 metabolic equilibrium by tailoring drug and dietary treatment in our patient affect by T1DM has a positive impact also in improving glycemic balance.

Metabolic stroke in a late-onset form of isolated sulfite oxidase deficiency.

We report the first case of late-onset isolated sulfite oxidase deficiency (ISOD) presenting with a stroke-like episode. Clinical, biochemical and neuroradiological features at diagnosis and during follow-up after dietary treatment intervention are described. Furthermore, pathogenic mechanisms possibly leading to stroke in ISOD are discussed.

Application of the WHOQOL-100 for the assessment of quality of life of adult patients with inherited metabolic diseases.

BACKGROUND: As advances in neonatal and pediatric care for patients affected by inherited metabolic diseases (IMD) improve their outcome and allow for better survival rates, there is a growing interest in the quality of life (QoL) of patients reaching adulthood. In order to address this subject we designed a study to evaluate the QoL of a group of adult IMD patients who are receiving various treatments, in a comprehensive manner. METHODS: A mixed-method study was conducted to assess the QoL in adult IMD patients. The multidimensional World Health Organization Quality of Life questionnaire (WHOQOL-100) was applied for quantitative evaluations, and an additional semi-standardized interview, was conducted for qualitative measurement of patients' perceptions of the impact of illness on their daily life, and the perceived adherence to their treatment recommendations. A total of 82 patients affected by IMD were enrolled. The inherited metabolic disorders included principally amino acids disorders, urea cycle defects, organic acidurias, carbohydrates disorders, and lysosomal disorders. The WHOQOL-100 and the semi-standardized interview were administered in a clinical setting to adult patients with IMD. RESULTS: The mean for the whole group indicates that adult patients with IMD can have a normal value of General QoL. Despite this value, the results of each domain show lower scores in the domains of perception of independence and quality of social relationships. We made a further analysis to compare the patients with dietary treatment with the patients with pharmacological treatment, and we observed a statistically significant difference in General QoL, in the Physical, Independence, Spiritual domains and in the facet of Medication. These results suggest that Global QoL measures might not be sufficient to assess the QoL for adult patients with IMD. Furthermore, the implementation of a qualitative semi-standardized interview, especially suitable for adult patients, added important features on illness perception and on perceived adherence to the treatment by adult IMD patients. CONCLUSION: In this study we underlined the importance of applying multidimensional instruments, like WHOQOL-100, to evaluate the quality of life of adult patients with IMD. The WHOQOL-100 has been demonstrated to be a valid instrument to measure the QoL of IMD patients. Moreover, the administration of a tailored psychometric instrument in combination with a qualitative interview may help us to better characterize special issues related to IMD. Indeed, other factors beyond the physical manifestations of the disease, such as psychological wellbeing, social behavior, illness perception and adherence to the treatment, strongly influence QoL and may serve as valid targets for intervention to improve patients' care. We believe this kind of approach is especially useful for adult patients with inherited metabolic diseases.

Long-term follow-up results in enzyme replacement therapy for Pompe disease: a case report.

Pompe disease (PD) is a metabolic myopathy caused by a deficiency of acid-alpha glucosidase (GAA), a lysosomal enzyme that cleaves glycogen. The classic infantile-onset form is characterised by severe hypotonia and cardiomyopathy. Untreated patients usually die within the first year of life due to cardiorespiratory failure. Several studies involving patients with infantile-onset PD have shown that enzyme replacement therapy (ERT) with alglucosidase alfa, recombinant human GAA (rhGAA), significantly prolongs survival, decreases cardiomegaly, and improves cardiac function and conduction abnormalities. However, the efficacy on motor, cognitive and social milestones appears to be more related to the condition of the patient before the start of treatment. To date, the sample of early diagnosed and treated patients is small and the length of follow-up is still limited. We report the results of a long-term follow-up of one patient presenting severe bradycardia and cardiomyopathy at birth, diagnosed in the third day of life and successfully treated by ERT. Serum muscle enzymes at diagnosis were AST 200 U/L, ALT 99 U/L and CPK 731 U/L (n.v. 0-295); the molecular study identified the homozygous missense mutation c.1933 G> A p.Asp645Asn (GAA exon 14). Left Ventricular Mass Index (LVMI) at baseline was 171 g/m(2) (Z-score = 4.3) and decreased to normal values since the 3-month follow-up. A muscle biopsy performed at 18 months after the start of therapy, showed only a low degree of muscle involvement. To our knowledge, this is the longest ERT treatment follow-up in a symptomatic neonatal patient with Pompe disease.

Sustained Epstein-Barr virus detection in paediatric liver transplantation. Insights into the occurrence of late PTLD.

Epstein-Barr virus (EBV) infection is the main cause of post-transplant lymphoproliferative disease (PTLD). Little is known on chronic carrier state and its relation with late PTLD. We aimed to study EBV infection in the long-term after paediatric liver transplantation (OLT). We conducted a retrospective review of 34 children monitored for a median of 5.8 years (range 1.5-17.7). 21 were IgG seronegative (group A) and 13 seropositive (group B) before OLT. Primary infection was the appearance of VCA-IgM or VCA-IgG or Real-Time Polymerase Chain Reaction (RT-PCR) in patients previously IgG seronegative; positive VCA-IgM or EA-IgG or RT-PCR lasting longer than 6 months was defined sustained viral detection (SVD). 18/21 patients of group A had a primary infection at a median time of 3 months after transplant (0.5-60). 14/18 of group A and 0/13 of group B had a SVD (P < 0.0001). Viral loads greater than 500 copies/10(5) mononuclear cells occurred in 12/18 patients in group A and 0/13 patients in group B (P < 0.0001). The 3 patients who developed late PTLD (median time after OLT 47 months, range 15-121) were from group A, and presented with SVD before developing PTLD. In conclusion, EBV infection in seronegative patients at OLT is associated with greater viral loads and sustained viral detection. Late PTLD occurred only in naïve patients with markers of SVD. Three to 4 monthly long-term monitoring of EBV in pre-OLT naïve patients might help preventing the occurrence of late PTLD.