Successful treatment of lathosterolosis: A rare defect in cholesterol biosynthesis-A case report and review of literature.

Lathosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis. It is caused by defects in the SC5D (sterol C5-desaturase) gene which encodes for the 3-beta-hydroxysteroid-delta-5-desaturase (also called sterol-C5-desaturase or lathosterol dehydrogenase). Only six cases have been described in the literature, but it is possible that a number of patients with milder forms of the condition might have been missed. Lathosterolosis manifests as microcephaly, bilateral cataracts, dysmorphism, limb anomalies, and developmental delay/intellectual disability. Liver involvement is variable and can range from normal liver function tests to portal fibrosis and cirrhosis. Diagnosis is made by demonstration of specific mutations in the SC5D gene and by plasma sterol analysis to confirm elevated lathosterol levels. In this report, we describe a girl with transaminitis in association with developmental delay/intellectual disability, facial dysmorphism, limb anomalies, and bilateral cataracts. Fibroscan showed severe liver fibrosis. Plasma sterol analysis and exome sequencing confirmed the diagnosis of lathosterolosis. Simvastatin treatment resulted in lowering of plasma lathosterol levels, improvement in transaminitis, and liver fibrosis grade, suggesting that children with this condition should be actively treated in order to prevent progression of liver disease.

Infant with hepatomegaly and hypoglycemia: A setting for fatty acid oxidation defects.

Fatty acid oxidation defects (FAOD) are one of the commonest metabolic liver diseases (MLDs) that can have varied presentations in different age groups. An infant presented with short history of jaundice and irritability, examination showed soft hepatomegaly. Investigations revealed non-ketotic hypoglycemia suggesting FAOD which was later confirmed as carnitine uptake defect with gas chromatography and mass spectrometry and mutation analysis. Patient improved with acute management of metabolic crisis, carnitine supplementation and corn starch therapy with reversal of encephalopathy, reduction in hepatomegaly, maintenance of euglycemia and improvement in liver function tests and creatine phosphokinase on follow up. Non-ketotic hypoglycemia is a characteristic finding in FAODs. Early diagnosis and appropriate management can result in excellent outcomes in patients with FAODs.

Vitamin D Deficiency and Parathyroid Response in Critically-ill Children: Association with Illness Severity and Clinical Outcomes.

OBJECTIVE: To determine the prevalence of vitamin D deficiency in critically ill children, and to study its association with parathyroid response, severity of illness and clinical outcomes. DESIGN: Prospective observational study. SETTING: Medical Pediatric Intensive Care Unit of a tertiary care centre of Northern India. PARTICIPANTS: 154 children in-patients: August 2011-January 2013. MAIN OUTCOME MEASURES: Vitamin D deficient children were (serum 25-hydroxy vitamin D <20 ug/mL) divided into parathyroid-responder [serum parathyroid hormone >65 pg/mL with 25(OH)D<20 ug/mL and/or calcium corrected for albumin <8.5 mg/dL] and non parathyroid-responder. Illness severity was assessed by Pediatric Index of Mortality-2 (PIM-2) score at admission. Biochemical parameters, illness severity scores and clinical outcomes were compared between parathyroid-responders and non-parathyroid-responders. RESULTS: Vitamin D deficiency and hypocalcemia were observed in 125 (83.1%) and 91 (59%) children, respectively at admission. There were no differences in illness severity score at admission, mortality rate and length of stay between vitamin D-deficient children and 19.8% of non-vitamin D-deficient children. Among Vitamin D-deficient children, parathyroid-responders had higher PIM-2 score at admission compared to non-parathyroid-responder [12.8 (7.4,20.6) vs. 6.5 (2.5,12.2), P=0.01]. However, there were no differences in other clinical outcomes between two groups. CONCLUSION: Critically ill children have high prevalence of vitamin D deficiency. Parathyroid gland response secondary to hypocalcemia or vitamin D defiency is impaired in critical illness.

Mesenchymal Hamartoma of Chest Wall in an Infant: Mimicking Persistent Pneumonia.

Mesenchymal Hamartoma of the chest wall (MHCW) is a very rare benign tumour. They are usually discovered in infancy. Spontaneous regression is known to occur in this benign condition. Management is surgical removal of mass if respiratory compromise is present. Conservative management is preferred modality in asymptomatic children as malignant transformation is not reported. Herein, we present a case of MHCW in a 5 month old infant presenting with acute respiratory distress with history of respiratory problem at 3 months of age. Child was suspected to have persistent pneumonia in view of radiological findings. Child's respiratory distress improved with antibiotics and bronchodilators. Respiratory symptoms in MHCW are due to extrinsic compression of lung parenchyma. Present case had respiratory symptoms with persistent radiological findings leading to suspicion of persistent pneumonia. His respiratory symptoms and exacerbation on follow up was attributed to hyper reactive airway disease and MHCW was managed conservatively. The non-neoplastic nature, characteristic presentation, histopathology, imaging modality and management options of MHCW are discussed.

Disseminated Mycobacterium avium complex infection in a child with partial dominant interferon gamma receptor 1 deficiency in India.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by clinical disease caused by weakly virulent mycobacteria. All genes mutated in MSMD patients are involved in IFN-γ immunity. Autosomal partial dominant (PD) interferon-γ receptor 1 (IFN-γR1) deficiency is the most frequent abnormality affecting the group of MSMD patients leading to impaired response of IFN-γ. We describe here a patient from India with disseminated infection due to Mycobacterium avium intracellulare (MAC) including multifocal osteomyelitis and BCG disease. A heterozygous mutation in exon 6 of IFNGR1 gene was identified, conferring an autosomal PD IFN-γR1 deficiency. Patient had recurrence of mycobacterial disease during antibiotic therapy for which subcutaneous IFN-γ was added as a modality of treatment for resistant MAC infection.

Unusual late neurological complication in a child after an Indian krait bite.

BACKGROUND: Neurological manifestations of elapid snakebites include neuromuscular paralysis and cerebrovascular complications. Autonomic manifestations are observed in almost two third of patients following moderate to severe envenomation. PATIENT SUMMARY: A 10-year-old boy presented with acute onset flaccid quadriparesis with encephalopathy, cranial neuropathy, and respiratory failure after bite of a common Indian krait. He also had features of autonomic instability in the form of hypertension and variable heart rate. Within 10 days, he was weaned from the ventilator and discharged on multiple oral antihypertensives. Within a week, he returned with focal status epilepticus. MRI of the brain suggested posterior reversible leukoencephalopathy. He recovered completely within 2 days with visual impairments while recovering. Within next 1 month, his antihypertensives were tapered completely. MRI of the brain, repeated after 3 months, confirmed complete resolution. CONCLUSIONS: This patient highlights the fact that posterior reversible leukoencephalopathy can be a late complication of Indian krait bite secondary to autonomic instability with systemic hypertension.

Leukodystrophy presenting as acute-onset polyradiculoneuropathy.

BACKGROUND: Sulfatides, the most abundant glycosphingolipids, are a major component of myelin. They are degraded by the combined action of sphingolipid activator protein and arylsulfatase A. Deficiency of either of these entities causes metachromatic leukodystrophy (MLD). On the basis of age of onset, this entity is divided into late infantile, juvenile, and adult subtypes. Late infantile form, the commonest subtype, can exhibit peripheral neuropathy as the initial manifestation. The other two forms usually manifest peripheral neuropathy later in the disease course. PATIENT: A 1.5-year-old girl with preexisting isolated motor delay presented with acute-onset ascending flaccid quadriparesis, ptosis, and respiratory failure. Ptosis and respiratory failure responded completely to intravenous immunoglobulin, whereas quadriparesis showed minimal improvement. Nerve biopsy revealed metachromatic granules with demyelination, and serum arylsulfatase A levels were undetectable. CONCLUSION: The severity and nature of the disease coupled with the response to immunotherapy makes this case unusual. This child may represent either an atypical presentation of MLD with coincidental response to immunotherapy or an episode of immune mediated neuropathy in an individual with already diseased nerves due to MLD.

Plasma exchange for hemolytic crisis and acute liver failure in Wilson disease.

Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism which primarily involves the liver and the central nervous system. Rarely, WD can present as acute liver failure (ALF) and this disease is universally fatal in the absence of liver transplantation. The authors report a young girl with WD ALF, who showed signs of recovery after prompt initiation of plasma exchange (PE) and chelation therapy. Though liver transplantation could not be done in this child and the child died 8 d after stopping PE, this case highlights that PE can be a successful medical treatment in WD ALF and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible.