At the end of the Session participants will: (1) Understand the signs and symptoms of lysosomal storage diseases. (2) Have the ability to identify the key diagnostic features and differentiate them from more common diseases. (3) Evaluate the ‘next steps’ to take after a diagnosis and how to maximize treatment for the patient.
Lipodystrophies are heterogeneous inherited or acquired disorders that are characterized by selective loss of adipose tissue and a predisposition to developing insulin resistance and its associated complications, such as diabetes mellitus, hypertriglyceridaemia and hepatic steatosis. The clinical diagnosis of lipodystrophy is made on the basis of a physical examination. Level loss of adipose tissue should be measured in a clinic, but is not crutial for the diagnosis. The prognosis for this disease is poor and patients suffer from a severe form of diabetes.
Clinical case: Child R.N., 05.15.2015, was charged in Scientific Center of Pediatrics and children surgery (SCPCS) with preliminary diagnosis: Malabsorption syndrome, fermentopathy, malnutrition, celiac disease. Complaints at admission: fatigue during feeding, weakness, anxiety, unstable stool (8 times a day), abdominal distension.
Health status at admission: Weight of the child was in compliance with the age, therefore, the diagnosis of malnutrition was disputable. However, a child had a elongation of the upper and lower extremities, enlargement of foot, hands. Hypertrophy of the muscular tissue of the upper and lower extremities with severe hypotrophy of gluteal muscles. Hypertrichosis, premature teething, hyperpigmentation in the axillary and inguinal regions. The enlargement of the external genitalia. Progeroid like phenotype. Hepatosplenomegaly. The following competing diagnoses were proposed: lysosomal acid lipase deficiency, progeria, celiac disease, pituitary microadenoma. The biochemistry analyses revealed the considerable increase of the total protein, a significant hypertriglyceridemia, high atherogenic index (12.3), high levels of LDL (up to 320 U/ml), cholesterol within references parameters. X rays the bones: without marked changes, bone age corresponds to the patient’s age. MRI of the abdomen and pelvic organs: a significant increase of the liver, the lower contour of the right lobe is located below the iliac crest, left lobe shifted the spleen downward.
Consilium conclusion: the diagnosis of acid lipase deficiency was disputable due to the lack of pathognomonic features of this disease. The study of acid lipase and beta-galactosidase activity was carried out on the basis of “Medical Genetic Research Center” Moscow, Russia. The enzyme activity in dried blood spots was within the reference range. The final diagnosis could be established only after a genetic test to identify the mutations that characterize the 4 main types of congenital generalized lipodystrophy. A homozygous mutation c.823C>T (p.R275*) on the BSCL2 gene was identified, which corresponds to the type 2 of congenital generalized lipodystrophy. Despite the fact that the second type of congenital lipodystrophy is more common than other types of the disease in the Kazakh population it was identified and confirmed for the first time. Since the prognosis of congenital lipodystrophy is unfavorable, specific therapy with Metreleptinshould be conducted. At the moment, the child’s condition is stable and is under the supervision of pediatricians
Scientific center of pediatrics and children surgery, Kazakhstan; email@example.com
Introduction: Classic galactosemia is a genetic condition, occurring in approximately 1 in 60,000 livebirths, inherited in an autosomal recessive pattern, associated with mutations in the GALT gene mutations, which predisposes to a compromised ability to metabolize galactose. It usually presents in the first days of life with jaundice, vomiting, hepatomegaly, failure to thrive, poor feeding, diarrhoea and sepsis. Although in some countries, its screening is routinely performed by newborn screening (NBS) program that does not happen in Portugal.
Clinical Case: We describe the case of a 2-month-year-old male child, without inbreeding and no relevant prenatal background, except for a minor unilateral hydronephrosis. He was admitted in our emergency department with paroxysmal nonepileptic events, mostly feed related, frequent regurgitation and failure to thrive. On physical examination, plagiocephaly and torticollis were noticed. Routine medical exams performed were normal, except for proteinuria. After medical discharge, he was referred to our out-patient clinic. His clinical evolution was characterized with maintenance by failure to thrive and developmental delay and Metabolic Disease Unit evaluation was requested. Inborn errors of metabolism (IEM) investigation revealed CDT > 5,3% (VR<2,6%), and renal tubular dysfunction. Urinary organic acids, sugars and polyols chromatographs where done. Ophthalmic evaluation was unremarkable. Brain MRI suggested IEM affecting mainly the white matter. Meanwhile CDG gene panel was inconclusive. A secondary CDG alteration where considered. Urinary profiles showed: polyol accumulation with Galactitol, 201mmol/mol Creatine (VR 6-71) and total Galactose on Guthries NBS was high: 36mg/dL e 52.3mg/dL. Compound heterozygosity mutation for Classic Galactosemia was detected. Galactose-restricted diet was initiated with great improvement in both his growth and development. CDT and urinary profile normalised and eGALP1P is now in good metabolic control reference pattern. Brain MRI was repeated by the age of two and significant regression of the signs seen before was noticed.
Conclusion: This case reveals an unusual form of presentation for a treatable disease. In our country Galactosemia is not on NBS panel so it was a diagnostic challenge that we have to consider when we have CDG profile alterations.
1Lower Alentejo Local Health Unit, Hospital José Joaquim Fernandes, Beja; 2Metabolic Diseases Unit, Pediatric’s Department of Santa Maria’s Medical Academic Centre, Hospital CHLN EPE, Lisbon; 3Metabolism and Genetics, Newborn Screening Unit, Human Genetic Department, Instituto Nacional de SaЬde Dr. Ricardo Jorge, OPorto; 4Metabolism and Genetics Laboratory, Pharmacy Faculty, University of Lisbon; firstname.lastname@example.org