Impact of COVID-19 pandemic on healthcare delivery for lysosomal storage disorders at a tertiary care public hospital in Mumbai.

Introduction: Management of lysosomal storage disorders (LSDs) requires periodic visits for medical surveillance and hospitalizations. Management of LSDs may have been adversely impacted during the COVID-19 pandemic. Objective: To identify the factors impacting health care for patients with LSDs during the COVID-19 pandemic. Methods: An observational study was conducted in Mumbai comparing infusion practices and reasons for missed infusions for 15 months before March 2020 versus two phases during the pandemic (April 2020-March 2021 and April 2021-March 2022) in patients receiving intravenous enzyme replacement therapy (ERT) and on oral substrate reduction therapy (SRT). Results: Fifteen patients with LSDs were enrolled. Before the pandemic, 6/13 (46%) were receiving ERT at the study site, 4/13 (31%) at a local hospital, and 3/13 (23%) at home; two were on SRT. The median distance traveled for receiving ERT was 37 km, and 4.4 infusions/patient were missed. From April 2020 to March 2021, two more patients opted for home ERT infusions. The median distance traveled for receiving ERT was 37 km, and 11.6 infusions/patient were missed. From April 2021 to March 2022, one more patient opted for home ERT infusions. The median distance traveled for receiving ERT was 7 km, and 5.6 infusions/patient were missed. The pandemic also affected SRT compliance adversely. For all patients, the cause of disrupted treatment was travel curbs (69%) and fear of getting COVID-19 infection (38%). Conclusions: Treatment of LSDs was disrupted during the pandemic, with an increase in missed ERT infusions and SRT doses.

Porphyrias: Uncommon disorders masquerading as common childhood diseases.

Porphyrias are a rare group of inborn errors of metabolism due to defects in the heme biosynthetic pathway. The biochemical hallmark is the overproduction of porphyrin precursors and porphyrin species. Afflicted patients present with a myriad of symptoms causing a diagnostic odyssey. Symptoms often overlap with those of common diseases and may be overlooked unless there is heightened clinical suspicion. We are reporting clinical features and diagnostic challenges in four pediatric patients having variegate porphyria, congenital erythropoietic porphyria, acute intermittent porphyria, and erythropoietic protoporphyria (EPP), who presented with diverse multisystem manifestations. This case series illustrates a logical analysis of symptoms and judicious selection of investigations and the role of genotyping in successfully diagnosing porphyrias.

Beta-thalassemia major complicated by intracranial hemorrhage and critical illness polyneuropathy.

Intracranial hemorrhage (ICH) is rarely seen in patients with thalassemia. A seven-year-old male, known case of beta-thalassemia major, on irregular packed cell transfusions (elsewhere) and non-compliant with chelation therapy, presented with congestive cardiac failure (Hb-3 gm/dl). He received three packed red cell transfusions over 7 days (cumulative volume 40 cc/kg). On the 9th day, he developed projectile vomiting and two episodes of generalized tonic-clonic convulsions with altered sensorium. He had exaggerated deep tendon reflexes and extensor plantars. CT-scan of brain revealed bilateral acute frontal hematoma with diffuse subarachnoid hemorrhage (frontal and parietal). Coagulation profile was normal. CT-angiography of brain showed diffuse focal areas of reduced caliber of anterior cerebral, middle cerebral, and basilar and internal carotid arteries (likely to be a spasmodic reaction to subarachnoid hemorrhage). He required mechanical ventilation for 4 days and conservative management for the hemorrhage. However, on the 18th day, he developed one episode of generalized tonic-clonic convulsion and his sensorium deteriorated further (without any new ICH) and required repeat mechanical ventilation for 12 days. On the 28th day, he was noticed to have quadriplegia (while on a ventilator). Nerve conduction study (42nd day) revealed severe motor axonal neuropathy (suggesting critical illness polyneuropathy). He improved with physiotherapy and could sit upright and speak sentences at discharge (59th day). The child recovered completely after 3 months. It is wise not to transfuse more than 20 cc/kg of packed red cell volume during each admission and not more than once in a week (exception being congestive cardiac failure) for thalassemia patients.

Managing pulmonary embolism secondary to suppurative deep vein thrombophlebitis due to community-acquired Staphylococcus aureus in a resource-poor setting.

Deep vein thrombosis and pulmonary thromboembolism are rare and life threatening emergencies in children. We report an 11-year old female who presented with acute complaints of high grade fever, pain in the left thigh and inability to walk and breathlessness since 6 days. On physical examination, there was a diffuse tender swelling of the left thigh, tachypnea, tachycardia with hyperdynamic precordium and bilateral basal crepitations. Ultrasonography and venous doppler of lower limbs showed mild effusion of left hip joint and thrombus in the left common femoral vein and left external iliac vein suggesting a diagnosis of septic arthritis with thrombophlebitis. The tachypnea and tachycardia which was out of proportion to fever and crepitations on auscultation prompted suspicion of an embolic phenomenon. Radiograph of the chest revealed multiple wedge shaped opacities in the right middle zone and lower zone suggestive of pulmonary embolism and left lower zone consolidation. For corroboration, computed tomography pulmonary angiography and computed tomography of abdomen was performed which showed pulmonary thromboembolism and deep venous thrombosis extending up to infrarenal inferior vena cava. On further workup, magnetic resonance imaging of hips showed left femoral osteomyelitis and multiple intramuscular abscesses in the muscles around the hip joint. Blood culture grew methicillin resistant Staphylococcus aureus. Antibiotics were changed according to culture sensitivity and there was a dramatic response. After four weeks of anticoagulation and antibiotics the child became asymptomatic and thrombus resolved. Thus, it is crucial to consider methicillin resistant Staphylococcus aureus infection as an important infection when we encounter such a clinical scenario. This case report highlights an unusual and potentially life threatening presentation of a virulent strain of a common pathogen, which when diagnosed was completely amenable to treatment.

Childhood cerebral X-linked adrenoleukodystrophy with atypical neuroimaging abnormalities and a novel mutation.

Childhood cerebral X-linked adrenoleukodystrophy (XALD) typically manifests with symptoms of adrenocortical insufficiency and a variety of neurocognitive and behavioral abnormalities. A major diagnostic clue is the characteristic neuroinflammatory parieto-occipital white matter lesions on magnetic resonance imaging. This study reports a 5-year 10-month old boy presenting with generalized skin hyperpigmentation since 3 years of age. Over the past 9 months, he had developed right-sided hemiparesis and speech and behavioral abnormalities, which had progressed over 5 months to bilateral hemiparesis. Retrospective analyses of serial brain magnetic resonance images revealed an unusual pattern of lesions involving the internal capsules, corticospinal tracts in the midbrain and brainstem, and cerebellar white matter. The clinical diagnosis of childhood cerebral adrenoleukodystrophy was confirmed by elevated basal levels of adrenocorticotropin hormone and plasma very long chain fatty acid levels. Additionally, sequencing of the ABCD1 gene revealed a novel mutation. The only specific palliative therapy that could be offered after diagnosis was dietary intervention. The patient died within 16 months of onset of neurological symptoms. Awareness that childhood cerebral XALD can present with atypical neuroimaging patterns early in its course may aid diagnosis at a stage when definitive treatment can be attempted and timely genetic counseling be offered to the family.

Rare disease heralded by pulmonary manifestations: Avoiding pitfalls of an "asthma" label.

Pulmonary manifestations are seldom recognized as symptoms of storage disorders. The report describes the diagnostic journey in a 30-month-old male infant, born of a third-degree consanguineous marriage referred to our institute as severe persistent asthma. History revealed that the child had progressively worsening breathlessness and persistent dry cough not associated with fever but accompanied by weight loss. On physical examination, there was growth failure, respiratory distress, clubbing, hepatosplenomegaly, and occasional rhonchi. Blood gas revealed hypoxemia which improved with oxygen administration. Plain X-rays and high-resolution computed tomography of the chest showed perihilar alveolar infiltrates and patchy consolidation. The clinicoradiological features did not support a diagnosis of asthma but favored interstitial lung disease (ILD). Bronchoalveolar lavage was performed as a first-tier investigation. It showed periodic acid-Schiff-negative foamy macrophages. The clues of consanguinity, visceromegaly, ILD, and foamy macrophages in the bronchoalveolar fluid prompted consideration of lysosomal storage disorders as the likely etiology. Gaucher disease and Niemann-Pick disease A/B were ruled out by enzyme estimation. Niemann-Pick disease type C was suspected and confirmed by detecting a homozygous mutation in the NPC2 gene. This case serves to caution physicians against labeling breathlessness in every toddler as asthma. It emphasizes the importance of searching for tell-tale signs such as clubbing and extrapulmonary clues which point to a systemic disease such as lysosomal storage disorders as a primary etiology of chronic respiratory symptoms.

Incomplete Kawasaki disease with recurrent skin peeling: a case report with the review of literature.

Kawasaki disease (KD) is an acute systemic vasculitis of unknown aetiology that has largely replaced rheumatic heart disease as a cause of acquired heart disease in children of many developed countries. We report a case of incomplete KD in a five-year-old girl. The diagnosis of incomplete KD was made after exclusion of conditions with similar presentation. She was treated with intravenous immunoglobulin following which she made an uneventful recovery but demonstrated thrombocytosis in the second week of convalescence. During the six-month follow up period, she had two episodes of recurrent skin peeling a phenomenon, which is recently reported with KD but not with atypical or incomplete KD. It is important for the treating physicians to become aware of the incomplete KD as prompt diagnosis and early treatment of these patients with intravenous immunoglobulin is vital for the prevention of lethal coronary complications. Physicians need to have a "high index of suspicion" for KD and even, higher for IKD.

Primary intraventricular haemorrhage: a rare presenting feature of arteriovenous malformation in children.

Two cases of arteriovenous malformation (AVM) of the brain presented with primary intraventricular haemorrhage in eleven and thirteen years old children, respectively. The cases responded favourably to therapy with steroids, anti-epileptic drugs and therapeutic embolisation in the former. Though such presentation accounts for 3% of the adult intracranial bleeds secondary to AVM rupture, the same has not been reported in children.

Infantile hemangioendothelioma.

Primary hepatic tumors are uncommon in children and account for only three per cent of the tumors in children. Infantile hemangioendothelioma is a rare benign hepatic tumor arising from mesenchymal tissue. Most of the cases present before six months. An unusual presentation and progression of infantile hemangioendothelioma is reported in a 19-month-old female child. The diagnosis was arrived at by radiological and histopathological examination. The patient underwent excision surgery, following which made an uneventful recovery. On follow-up at six months, patient was asymptomatic with no evidence of recurrence.

Ovarian dysgenesis with balanced autosomal translocation.

Autosomal translocations are rare in the patients with ovarian dysgenesis. An 18-year-old female who presented with primary amenorrhoea had hypergonadotropic hypogonadism and streak ovaries with hypoplastic uterus. Karyotype analysis revealed a balanced autosomal translocation involving chromosomes 1 and 11. The probable role of autosomal translocations in ovarian dysgenesis has been discussed.

Neurofibromatosis-Noonan syndrome or LEOPARD Syndrome? A clinical dilemma.

Neurofibromatosis (NF), Noonan syndrome (NS), and LEOPARD syndrome are all autosomal dominant conditions, each being a distinct clinical entity by itself. Rarely, one encounters cases with features of NF and NS and is termed as the 'Neurofibromatosis-Noonan syndrome' (NF-NS). The authors report a clinical dilemma with major clinical features of the NF-NS syndrome and LEOPARD syndrome co-existing in the same patient. Also, features of Noonan syndrome and LEOPARD syndrome are compared with the case reported.