Subtype variability, virological response and drug resistance assessed on dried blood spots collected from HIV patients on antiretroviral therapy in Angola.

BACKGROUND: Subtype variability may influence treatment response and selection of drug resistance mutations in HIV-positive patients on antiretroviral therapy. PATIENTS AND METHODS: A retrospective study was performed on specimens collected on dried blood spots (DBS) from HIV-positive individuals receiving antiretroviral therapy in Luanda, Angola. HIV-RNA, drug resistance mutations and subtypes were examined in 294 HIV-positive patients treated with two nucleoside analogues (NA) plus one non-nucleoside reverse transcriptase inhibitor (NNRTI). RESULTS: Overall, 217 (74%) had <1000 HIV-RNA copies/mL after a median of 12 months (range 7-24) of therapy. CD4 count was significantly higher in subjects with undetectable viraemia compared with viraemic patients (294 versus 220 cells/mm3; P = 0.003). Reverse transcriptase and/or gp41 genes could be genotyped in only 45 (58%) of viraemic patients, probably due to poor storage conditions of DBS. The most frequent resistance mutations were M184V (70%) and K103N (39%); 65% had mutations conferring resistance to both NA and NNRTI. Only five patients did not show resistance mutations. A wide HIV-1 subtype heterogeneity was found: 6 C (18.2%), 2 F (6%), 2 H (6%), 1 D (3%), 1 G (3%), 8 CRF02_AG (24.2%), 2 CRF06 (6%), 1 CRF01_AE (3%), 1 CRF14_BG (3%), 1 CRF25 (3%) and 1 CRF19 (3%). HIV clade could not be assigned in 7 (21%). CONCLUSIONS: Nearly three-quarters of HIV-positive individuals who began an NNRTI-based triple regimen in Angola showed undetectable viraemia after a median of 12 months of therapy, a rate similar to that reported in Western countries. Specimens collected on DBS may allow monitoring of treatment response in resource-limited regions, although adequate temperature and humidity storage conditions are important to ensure RNA stability and further successful testing.

Maturity onset diabetes of young type 2 due to a novel de novo GKC mutation.

Maturity Onset Diabetes of Young (MODY) is a heterogeneous group of monogenic disorders that result in ß-cell dysfunction, with an estimated prevalence of 1%-2% in industrialized countries. MODY generally occurs in non-obese patients with negative autoantibodies presenting with mild to moderate hyperglycemia. The clinical features of the patients are heterogeneous, depending on the different genetic subtypes. We pretend to report a case of MODY type 2 caused by a novel de novo CGK mutation, highlighting the importance of the differential diagnosis in pediatric diabetes. A 13-year-old, healthy and non-obese girl was admitted for investigation of recurrent hyperglycemia episodes. She presented with persistent high levels of fasting blood glycemia (> 11.1 mmol/L) and had no familial history of diabetes. The blood glucose profile revealed an impaired fasting glucose of 124 mg/dL (6,9 mmol/L) with a normal oral glucose tolerance test. Fasting insulinemia was 15 mg/dL (90.1 pmol/L), HOMA-IR was 3.9 and hemoglobin A1c was 7.1%. Pancreatic autoantibodies were negative. Genetic testing identified a novel missense heterozygous mutation in exon 5 of GCK gene c.509G > T (p.Gly170Val), not present on the parents. This result established the diagnosis of MODY type 2. Clinical identification of patients with MODY remains a diagnostic challenge, especially when familial history is absent. Molecular diagnosis is very important for establishing an individualized treatment and providing a long term prognosis for each type of MODY.

Berardinelli-Seip syndrome: highlight of treatment challenge.

Berardinelli-Seip congenital lipodystrophy (BSCL) syndrome is a rare autosomal-recessive disease characterised by lipoatrophy and associated with deregulations of glycidic and lipid metabolism. We report three BSCL cases with its typical clinical picture and complications. Clinically, they all show marked atrophy of adipose tissue, acromegaly, acanthosis nigricans and tall stature. Two cases present attention deficit hyperactivity and developmental learning disorders; another patient has hypertrophic myocardiopathy and polycystic ovary syndrome. In all the cases AGPAT2 was the identified mutation. All the cases present hypertriglyceridemia. One case has developed hyperinsulinism controlled with metformin and another case already has type 2 diabetes with a difficult clinical control. There is no curative treatment and the current treatment options are based only on symptomatic control of the complications. Recently, published studies showed that leptin-replacement therapy appears a promising tool in the metabolic correction of BSCL complications, highlighting the importance of further investigations in BSCL treatment.

Septo-optic dysplasia: fitting the pieces together.

A 7-year-old boy was admitted for a general tonic-clonic seizure with severe hypoglycaemia (1.39 mmol/l). His medical history was remarkable for a congenital left eye strabismus, unilateral cryptorchidism and three previous episodes of hypoglycaemic seizures with inconclusive metabolical and neurological investigations. Physical examination revealed a hoarse tone voice, dry skin, cold extremities and height in the third percentile (target height between 50th and 85th percentile). Left wrist radiography revealed a bone age of 4.5 years ±6 months Laboratory studies confirmed growth hormone deficiency and central hypothyroidism. The brain MRI showed an ectopic neurohypophysis. Neuroophthalmology investigation revealed left optic nerve hypoplasia and septo-optic dysplasia was then diagnosed. Thyroid and recombinant growth hormone replacement were started showing clinical improvement. A detailed clinical history and a careful physical examination in children presenting with multiple clinical signs of hypopituitarism may lead to a timely diagnosis, avoiding clinical morbidity associated to untreated hormonal abnormalities.

Hypovitaminosis D and severe hypocalcaemia: the rebirth of an old disease.

Vitamin D deficiency, once thought to be eradicated, is becoming a frequent occurence in children, caused mainly by dietary insufficiency. The classical manifestation is rickets, but in infants severe hypocalcaemia may present as stridor, tetany, seizures or, rarely, heart disease. Here, we describe four infants who presented with complications of severe hypocalcaemia secondary to nutritional vitamin D deficiency. (1) Female, 4 months old, several spasms. (2) Male, 8 days old, generalised tonic-clonic seizure. (3) Male, 9 months old, tetany. (4) Male, 4 months old, cardiogenic shock. The cases highlight the importance of child vitamin D supplementation from birth and throughout childhood. We also note that the vitamin D state should be evaluated by the 25(OH)-D value and not the 1,25(OH)2-D.

Juvenile systemic lupus erythematosus with primary neuropsychiatric presentation.

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple manifestations in several organs and systems. Neuropsychiatric manifestations can occur in 22-95% of paediatric cases, being much less frequent as an initial clinical event. We report a case of SLE, presenting primarily with neuropsychiatric symptoms. An African-descendant 7-year-old girl was admitted with a 4-day history of ataxia, diplopia and morning vomiting, as well as severe headache, psychiatric symptoms and cognitive dysfunction beginning 1 year prior to admission. Brain MRI was suggestive of encephalitis. Investigation excluded infectious aetiology. Immunological markers revealed high titre of antinuclear and anti-double-stranded DNA antibodies. Neuropsychiatric lupus (NPL) was considered, and cyclophosphamide and methylprednisolone pulses were started, with good initial response. Clinical deterioration motivated therapy with azathioprine with subsequent clinical stabilisation and a latent cognitive dysfunction. In unusual encephalitis presentation, a wide range of differential diagnosis has to be considered. Primary NPL presents difficult diagnostic and therapeutic challenges.

Maturity onset diabetes of young type 2 due to a novel de novo GKC mutation / Diabetes monogênica tipo MODY com início na juventude causado por uma mutação GKC de novo não descrita anteriormente

Maturity Onset Diabetes of Young (MODY) is a heterogeneous group of monogenic disorders that result in β-cell dysfunction, with an estimated prevalence of 1%-2% in industrialized countries. MODY generally occurs in non-obese patients with negative autoantibodies presenting with mild to moderate hyperglycemia. The clinical features of the patients are heterogeneous, depending on the different genetic subtypes. We pretend to report a case of MODY type 2 caused by a novel de novo CGK mutation, highlighting the importance of the differential diagnosis in pediatric diabetes. A 13-year-old, healthy and non-obese girl was admitted for investigation of recurrent hyperglycemia episodes. She presented with persistent high levels of fasting blood glycemia (> 11.1 mmol/L) and had no familial history of diabetes. The blood glucose profile revealed an impaired fasting glucose of 124 mg/dL (6,9 mmol/L) with a normal oral glucose tolerance test. Fasting insulinemia was 15 mg/dL (90.1 pmol/L), HOMA-IR was 3.9 and hemoglobin A1c was 7.1%. Pancreatic autoantibodies were negative. Genetic testing identified a novel missense heterozygous mutation in exon 5 of GCK gene c.509G > T (p.Gly170Val), not present on the parents. This result established the diagnosis of MODY type 2. Clinical identification of patients with MODY remains a diagnostic challenge, especially when familial history is absent. Molecular diagnosis is very important for establishing an individualized treatment and providing a long term prognosis for each type of MODY.

O diabetes da maturidade com início na juventude (MODY) é um grupo heterogêneo de doenças monogênicas que resultam em disfunção das células β, com uma prevalência estimada de 1-2% nos países industrializados. O MODY geralmente ocorre em pacientes não obesos, negativos para autoanticorpos e que apresentam hiperglicemia de leve a moderada. As características clínicas dos pacientes são heterogêneas e dependem do subtipo genético. Pretende-se relatar um caso de MODY tipo 2 causado por uma mutação GKC de novo não descrita anteriormente, demonstrando a importância do diagnóstico diferencial no diabetes pediátrico. Uma menina de 13 anos de idade, saudável e não obesa, foi admitida em um hospital para investigação de episódios recorrentes de hiperglicemia. Ela apresentava níveis altos e persistentes de glicemia de jejum (> 11,1 mmol/L) e não havia histórico familiar de diabetes. O perfil glicêmico sanguíneo revelou glicose de jejum de 124 mg/dL (6,9 mmol/L), com resultados normais no teste oral de tolerância à glicose. O resultado da insulinemia de jejum foi 15 mg/dL (90,1 pmol/L), do HOMA-IR foi 3,9 e da hemoglobina A1c foi de 7,1%. Os autoanticorpos pancreáticos foram negativos. A análise genética identificou uma nova mutação heterozigota missense no éxon 5 do gene GCK c.509G > T (p.Gly170Val), não encontrada nos país. Esse resultado estabeleceu o diagnóstico de MODY tipo 2. A identificação clínica dos pacientes com MODY permanece um desafio diagnóstico, especialmente quando não existe um histórico familiar. O diagnóstico molecular é muito importante para se estabelecer um tratamento individualizado e oferecer um prognóstico de longo prazo para cada tipo de MODY.

Aleitamento materno e excesso de peso em crianças na idade escolar / Breastfeeding and overweight in school-aged children

Objetivos: Avaliar a associação entre a duração do aleitamento materno e o risco de sobrepeso e obesidade em crianças de idade escolar.Métodos: Estudo transversal com 125 crianças entre 5 e 10 anos de idade, atendidas em um centro de saúde de Lisboa, Portugal. Foram aferidos altura e peso em consulta de rotina. As variáveis peso ao nascer, duração do aleitamento materno, estilo de vida da criança, hábitos tabágicos na gravidez, estado nutricional e escolaridade da mãe foram obtidas em questionários preenchidos pelos pais. Definiu-se sobrepeso e obesidade como índice de massa corporal igual ou superior ao percentil 85 nas tabelas do ano 2000 do Center for Disease Control and Prevention. Utilizaram-se modelos de regressão logística para avaliar a associação entre duração do aleitamento materno e risco de sobrepeso e obesidade.Resultados: A prevalência de sobrepeso e obesidade foi 23,2%. Entre as 125 crianças, 28,8% foram amamentadas durante pelo menos seis meses e 25,6% nunca foram amamentadas. Identificaram-se como fatores de risco para sobrepeso e obesidade: hábitos alimentares inadequados, exercício físico insuficiente e sobrepeso materno. Verificou-se um claro efeito dose-resposta entre a duração do aleitamento materno e o risco de sobrepeso e obesidade. Após controle das variáveis de confundimento, o aleitamento materno, durante pelo menos seis meses, apresentou um efeito protetor contra o sobrepeso e obesidade (odds ratio: 0,016; intervalo de confiança 95%: 0,001-0,67).Conclusões: Neste estudo, maior duração do aleitamento materno associou-se à diminuição do risco de sobrepeso e obesidade em idade escolar. Estes resultados realçam a importância do aleitamento materno no risco de obesidade infantil.

Aims: To analyze the association of breastfeeding and the risk of overweight and obesity in school-aged children.Methods: Cross-sectional study with 125 children, aged 5 to 10 years old, enrolled in a primary health care center in Lisbon. Height and weight were measured during routine consultation. Other variables? breastfeeding duration, birth weight, lifestyle factors, smoking habits during pregnancy, mother nutritional state and education ? were collected based on questionnaires completed by parents. Overweight and obesity were defined as body mass index equal or above the 85th percentile based on the 2000 Center for Disease Control and Prevention growth charts. Association between breastfeeding and overweight and obesity was performed using logistic regression models.Results: Prevalence of overweight and obesity was 23.2%. Among the 125 children, 28.8% were breastfed for six or more months and 25.6% were never breastfed. Inadequate diet, insufficient physical activity and mother´s overweight were identified as risk factors for children´s overweight and obesity. A doseresponse effect was identified between the duration of breastfeeding and the risk of overweight and obesity. After adjusting for confounding variables, breastfeeding for at least six months remained a significant protective factor against the development of overweight (odds ratio: 0.016; 95% confidence interval: 0.001-0.67).Conclusions: In this study, prolonged breastfeeding was associated with a reduced risk of overweight and obesity in school-aged children. These results emphasize the importance of breastfeeding on the risk of childhood obesity.