Objectives Our aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme. Methods This cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records. Results We collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous β-thalassemia, 360 patients (20.3%) had hemoglobin E β-thalassemia, and 50 patients (2%) had sickle β-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with β-thalassaemia varied between 45–55, with little evidence of reduction over 19 years. Conclusions Central coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.
Background Tetrahydrobiopterin (BH 4 ) deficiencies are disorders affecting phenylalanine homeostasis, and catecholamine and serotonin biosynthesis. GTP-Cyclohydrolase I deficiency (OMIM 600225) is an extremely rare variant of inborn error of BH 4 synthesis which exists in recessive and dominant forms. The recessive form presents with complex neurological and autonomic dysfunction whilst the dominant form presents as Dopa-responsive dystonia. Case presentation We describe a South Asian child who initially presented with neurological dysfunction and recurrent vomiting and later developed recurrent hyperthermia for several months. The child did not have screening for hyperphenylalaninemia at birth and was found to have marked hyperphenylalaninemia after clinical presentation at 5 months. Further evaluation revealed BH 4 deficiency. GTP-Cyclohydrolase I deficiency (GTPCH) was identified based on normal dihydro pteridine reductase activity and markedly reduced neopterin in dried blood spot test. After institution of treatment and control of high phenylalanine levels, clinical deterioration decelerated yet with noticeable residual neurological dysfunction. Conclusion To authors’ knowledge, this is first report of GTPCH deficiency in a South Asian child. The case highlights practical issues regarding diagnosis of GTPCH deficiency, especially in countries without broader universal newborn screening programs for early detection of inherited metabolic disorders. Testing for GTPCH deficiency should be considered for patients with unexplained neurological and autonomic symptoms following initial metabolic screen.
Background Van Wyk-Grumbach syndrome refers to the development of isosexual precocious pseudopuberty and multicystic enlarged ovaries in the presence of hypothyroidism and delayed bone age. It is a rare presentation of untreated hypothyroidism. The prepubertal response in Van Wyk-Grumbach syndrome is always isosexual and mediated by very high thyroid-stimulating hormone levels acting through the follicle-stimulating hormone receptors inducing a follicle-stimulating hormonal effect. Early recognition and thyroid hormone replacement can completely regress precocious puberty and ovarian enlargement, while improving the final height achievement. Oligosyndactly is a congenital bony abnormality and can manifest either as an isolated malformation or as a component of a syndromic diagnosis. However, development of hypothyroidism in children with this peculiar bony deformity has rarely been described in the medical literature, with the exception of Cenani-Lenz Syndactyly syndrome. Case presentation We report the case of a 6-year-old Sri Lankan girl who presented with a 2-day history of vaginal bleeding and exertional dyspnea. She had marked short stature (well below −3 standard deviations) with an upper segment to lower segment ratio of 1.47. This girl had isolated breast development of Tanner stage 2. She was diagnosed to have acquired hypothyroidism secondary to autoimmune thyroiditis and also had macrocytic anemia, pericardial effusion, gonadotropin-releasing hormone-independent precocious puberty with radiological evidence of pubertal changes in the uterus, and multicystic ovaries. Interestingly, she also had post-axial oligosyndactyly in both feet and right-sided clubfoot. The diagnosis of Van Wyk-Grumbach syndrome was made based on the clinical and laboratory features. Her symptoms were successfully managed with L-thyroxine therapy. Conclusions Acquired hypothyroidism is a relatively common endocrine disorder among children and early recognition is important to prevent serious complications like Van Wyk-Grumbach syndrome. Sexual precocity with delayed bone age and stunting should direct our minds toward this unique diagnosis. It is always necessary to identify the other associated anomalies in addition to the primary diagnosis since these features may direct to a syndromic diagnosis.
Background Very long-chain acyl-coenzyme-A dehydrogenase deficiency is a rare, severe life-threatening metabolic disorder of mitochondrial fatty acid oxidation, caused by mutations in ACADVL gene. Here we present a genetically confirmed case of a South Asian baby girl with severe, early-onset form of very long-chain acyl-coenzyme-A dehydrogenase deficiency due to a novel mutation in ACADVL gene. Case presentation Index case was the second baby girl of second-degree consanguineous South Asian parents. She had an uncomplicated antenatal period and was born by spontaneous vaginal delivery at term with a birth weight of 2910 g. She had been noted to have fair skin complexion, hypotonia, and 3 cm firm hepatomegaly. Since birth, the baby developed grunting, poor feeding, and recurrent episodes of symptomatic hypoglycemia and convulsions with multiple semiology. Her septic screening and urine ketone bodies were negative. The baby had high anion gap metabolic acidosis and elevated transaminases and serum creatine phosphokinase levels. Echocardiogram at 4 months revealed bilateral ventricular hypertrophy. Acylcarnitine profile revealed elevated concentrations of tetradecanoylcarnitine (C14), tetradecanoylcarnitine C14:1, and C14:1/C16. Unfortunately, the baby died due to intercurrent respiratory illness at 4 months of age. Sequence analysis of ACADVL gene in perimortem blood sample revealed homozygous frame shift novel variant NM_001270447.1, c.711_712del p.(Phe237Leufs*38), which confirmed the diagnosis of very long-chain acyl-coenzyme-A dehydrogenase deficiency. Conclusions This case demonstrates the importance of early diagnosis and management of very long-chain acyl-coenzyme-A dehydrogenase deficiency in improving the outcome of the patients. Implementation of newborn screening using tandem mass spectrometry in Sri Lanka will be beneficial to reduce the morbidity and mortality of treatable disorders of inborn errors.
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