Abetalipoproteinemia - A Rare Disease Presenting as Bleeding Disorder

A 5-month-old child presented to the Paediatric Outpatient Department with complaints of fever, loose stools, blood in stool, and multiple subcutaneous swellings over the chest wall. The patient was given antibiotics and treated for acute gastroenteritis with a possibility of component of cow’s milk allergy also being considered. The routine blood counts revealed platelet count of 4.94 K / mL, along with Hb 10.2 g / dL, MCV - 80 fL, WBC - 13.6 x 109 / L. An LDH of 512 U / L (normal up to 451 U / L) and ESR of 2 mm / 1st hr. Liver function tests were within normal range. Her preliminary coagulation screening test showed both PT as well as aPTT to be prolonged beyond 120 sec each. She was further sent for complete laboratory evaluation for bleeding disorder. In view of the history of foul smelling stools, suggesting malabsorption, stool sample was analysed which showed presence of fat globules. USG was reported as normal study. Blood group was O positive.Abetalipoproteinemia is a very rare metabolic, autosomal recessive disease resulting from mutations encoding microsomal triglyceride transfer protein (MTP) leading to deficiencies in the apolipoproteins B-48 and B-100 with reported prevalence of less than one case per 100,000. Typical manifestations are failure to thrive, hypocholesterolaemia and fat malabsorption. Other features like fatty liver, acanthocytosis, and anaemia are usually present in infancy and neuro-ocular complications during adolescence. Early diagnosis and management can prevent disease progression

Bardet–Biedl syndrome: Genetics, molecular pathophysiology, and disease management.

Primary cilia play a key role in sensory perception and various signaling pathways. Any defect in them leads to group of disorders called ciliopathies, and Bardet–Biedl syndrome (BBS, OMIM 209900) is one among them. The disorder is clinically and genetically heterogeneous, with various primary and secondary clinical manifestations, and shows autosomal recessive inheritance and highly prevalent in inbred/consanguineous populations. The disease mapped to at least twenty different genes (BBS1-BBS20), follow oligogenic inheritance pattern. BBS proteins localizes to the centerosome and regulates the biogenesis and functions of the cilia. In BBS, the functioning of various systemic organs (with ciliated cells) gets deranged and results in systemic manifestations. Certain components of the disease (such as obesity, diabetes, and renal problems) when noticed earlier offer a disease management benefit to the patients. However, the awareness of the disease is comparatively low and most often noticed only after severe vision loss in patients, which is usually in the first decade of the patient’s age. In the current review, we have provided the recent updates retrieved from various types of scientific literature through journals, on the genetics, its molecular relevance, and the clinical outcome in BBS. The review in nutshell would provide the basic awareness of the disease that will have an impact in disease management and counseling benefits to the patients and their families.

Clinical utility of multiplex ligation-dependent probe amplification technique in identification of aetiology of unexplained mental retardation: A study in 203 Indian patients.

Background & objectives: Developmental delay (DD)/mental retardation also described as intellectual disability (ID), is seen in 1-3 per cent of general population. Diagnosis continues to be a challenge at clinical level. With the advancement of new molecular cytogenetic techniques such as cytogenetic microarray (CMA), multiplex ligation-dependent probe amplification (MLPA) techniques, many microdeletion/microduplication syndromes with DD/ID are now delineated. MLPA technique can probe 40-50 genomic regions in a single reaction and is being used for evaluation of cases with DD/ID. In this study we evaluated the clinical utility of MLPA techniques with different probe sets to identify the aetiology of unexplained mental retardation in patients with ID/DD. Methods: A total of 203 randomly selected DD/ID cases with/without malformations were studied. MLPA probe sets for subtelomeric regions (P070/P036) and common microdeletions/microduplications (P245-A2) and X-chromosome (P106) were used. Positive cases with MLPA technique were confirmed using either fl uorescence in situ hybridization (FISH) or follow up confirmatory MLPA probe sets. Results: The overall detection rate was found to be 9.3 per cent (19 out of 203). The detection rates were 6.9 and 7.4 per cent for common microdeletion/microduplication and subtelomeric probe sets, respectively. No abnormality was detected with probe set for X-linked ID. The subtelomeric abnormalities detected included deletions of 1p36.33, 4p, 5p, 9p, 9q, 13q telomeric regions and duplication of 9pter. The deletions/duplications detected in non telomeric regions include regions for Prader Willi/Angelman regions, Williams syndrome, Smith Magenis syndrome and Velocardiofacial syndrome. Interpretation & conclusions: Our results show that the use of P245-A2 and P070/P036-E1 probes gives good diagnostic yield. Though MLPA cannot probe the whole genome like cytogenetic microarray, due to its ease and relative low cost it is an important technique for evaluation of cases with DD/ID.

Crigler-Najjar syndrome type 2: Novel UGT1A1 mutation.

Crigler-Najjar syndrome type 2 is a rare cause for persistent unconjugated hyperbilirubinemia, inherited in an autosomal recessive manner. Even though it is compatible with normal life span, in the absence of prompt suspicion and intensive management it can prove fatal not only in the neonatal period but also during adult life. Here, we describe a case with a novel homozygous UGT1A1 p.Pro176Leu mutation.

Lipoprotein Lipase Deficiency in an Infant.

Patients with isolated hypertriglyceridemia usually present with recurrent abdominal pain, pancreatitis, eruptive xanthomas, lipemia retinalis and hepatosplenomegaly. We describe the diagnosis and treatment of an infant with severe hypertriglyceridemia. The child was found to be heterozygous for two novel mutations in the lipoprotein lipase gene.

Congenital Myotonic Dystrophy with Asymptomatic Mother.

Myotonic dystrophy is an autosomal dominant neuromuscular disorder characterised by extreme pleiotropism and variability in disease expression. A congenital form is rare and is observed in infants born to symptomatic mothers with multisystem involvement. We report a case of a neonate with congenital myotonic dystrophy born to an asymptomatic mother.

Carbonic anhydrase II deficiency: A novel mutation.

Carbonic anhydrase II (CA II) deficiency is an extremely rare autosomal recessive disorder, characterised by a triad of osteopetrosis, renal tubular acidosis and cerebral calcifications. A 12-year-old boy with classical features of CA II deficiency is reported who was found to be homozygous for the mutation in CA II gene and parents were heterozygous for the same mutation .To the best of our knowledge this is the first case report of mutation proven CA II deficiency from India.

Sly Disease: Mucopolysaccharidosis Type VII.

A 6 month-old infant presenting with severe mitral regurgitation was found to have hepatosplenomegaly, corneal clouding, and Alder-Reilly granules in the leucocytes. Extremely low levels of beta glucuronidase confirmed the diagnosis of Sly disease (Mucopolysaccharidosis VII). This is the first case of MPS VII reported from India.

Partial trisomy 9q due to maternal 9q 17q translocation.

Partial Trisomy 9q is a unique chromosomal anomaly with a distinctive phenotype. Only 5 cases have been reported in the literature till now. A large family with four affected children was studied in detail and was compared with the five previously reported cases. Determination of this novel balanced translocation in their family had helped us to offer prenatal diagnosis. This presentation is unique as even though partial trisomy 9q has been reported earlier with 9/17 translocations, our family is the first to have a translocation between q arms of chromosomes 9 and 17.