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Biomedical subjects

Tipu Sultan

Publications and source records attributed to Tipu Sultan.

6 recordsLinked to original sources
PubMed2026

COXFA4L2 upregulation preserves residual cytochrome c oxidase activity in COXFA4-related Leigh-like encephalopathy.

Primary mitochondrial diseases (PMDs) affect approximately 1 in 4300 individuals and cause early-onset neuromuscular and multisystem dysfunction with reduced lifespan. They result from pathogenic variants in mitochondrial or nuclear DNA that impair oxidative phosphorylation. Cytochrome c oxidase (COX; complex IV) deficiency is a well-established cause of PMD, leading to a broad spectrum of phenotypes. COXFA4 (cytochrome c oxidase subunit FA4), formerly NDUFA4, is a nuclear-encoded COX subunit, but its role in disease remains poorly defined. We report the largest genetically confirmed cohort of COXFA4-related PMD to date, comprising 13 individuals from 12 families with biallelic pathogenic COXFA4 variants. All present with Leigh-like encephalopathy and complete loss of COXFA4 protein; however, patient-derived fibroblasts retain residual COX activity, with upregulation of COXFA4L2 (cytochrome c oxidase subunit FA4-like 2), a poorly characterised paralog. Here, we show that COXFA4 is a late-stage COX assembly subunit and identify a paralog-mediated compensatory mechanism with translational potential.

Humans↗
PubMed2026

Unveiling clinical and genetic landscapes of MMA and CBS: insights from whole exome sequencing in a tertiary care setting.

BACKGROUND: MMA and CBS deficiency are rare autosomal recessive metabolic disorders caused by defects in cobalamin metabolism and cystathionine-beta-synthase activity, respectively. Advanced molecular genetic techniques, have become essential for diagnosing these conditions. This study aimed to analyze the genetic variations in three MMA and four CBS deficiency cases using WES and correlate the findings with clinical, biochemical, and treatment outcomes. METHODS: Clinical evaluation, biochemical testing, neuroimaging, and WES were performed. WES data were analyzed using the reference genome GRCh37, and variants were classified according to ACMG guidelines. Treatment outcomes were monitored for three months post-intervention. RESULTS: In MMA cases, a homozygous pathogenic variant (c.394 C > T, p.Arg132Ter) in MMACHC was identified in all three patients. Biochemical abnormalities included methylmalonic aciduria, elevated homocysteine, and megaloblastic anemia. Hydroxycobalamin therapy improved behavioral, cognitive, and dermatological symptoms, though residual neuropathy persisted in one case. In CBS deficiency, pathogenic variants in CBS (c.992 C > T, p.Ala331Val; c.862 G > A, p.Ala288Thr; c.700 G > A, p.Asp234Asn) were identified. Clinical features included developmental delayed milestones, lens dislocation, and vascular complications. Treatment outcomes varied based on early diagnosis and compliance. CONCLUSION: This study highlights the importance of newborn screening program with WES in diagnosing and managing MMA and CBS deficiency, facilitating early intervention, improving clinical outcomes, and supporting precision medicine approaches. IMPACT: Early newborn screening and diagnosis are critical for effective treatment and improved patient outcomes. Novel clinical and pathogenic variants will expand the current understanding of these disorders. WES enhances the diagnostic precision for MMA and CBS deficiency, facilitating timely intervention and superior clinical management. Accurate and early detection of treatable IEMs through NBS can significantly reduce disease burden and healthcare costs.

Child, Preschool↗
PubMed2006

The spectrum of neurodegeneration in children.

OBJECTIVE: To find out the spectrum of diagnosis, clinical presentation and role of neuroimaging in neurodegenerative disorders of childhood. DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Neurology, Children's Hospital, Lahore from June, 2004 to May, 2005. PATIENTS AND METHODS: A total of 1273 patients were admitted in the Neurology Department in the said period. Out of them, 66 children fulfilled the inclusion criteria. History, clinical examination and relevant investigations were carried out and proformas were filled. Data was analyzed for descriptive statistics. RESULTS: In a total sample of 66, the male to female ratio was 1.4:1. Age range was one to twelve years. Metachromatic leukodystrophy was the predominant type seen in 14 (21%), followed by 11 cases of adrenoleukodystrophy (16%) and 8 patients with SSPE (12%). Six children (9.8%) had Wilson's disease. Five cases (7.5%) were diagnosed as Friedrich ataxia, 4 cases (4%) as lipidosis, 3 case as Gaucher's disease (4.5%), and two cases (3%) each as Alexander disease, and Hellervorden-spatz disease; and one case each as multiple sclerosis and ataxia telangiectasia. In 6 cases, final diagnosis could not be made. MRI and CT scan of brain were done in 71% and 41% patients only. Furdos copy (in 65%), CSF examination in 59% and EEG in 56% were main non-imaging investigations utilized for diagnosis. CONCLUSION: Degenerative brain diseases are not an uncommon entity in paediatric population. Commonest presentation is regression of milestones, though, it may be variable. Because of limited diagnostic modalities, brain imaging has significant value. Facilities for enzyme studies should also be available at tertiary care hospitals.

Brain↗
PubMed2006

Does early referral to tertiary care decrease the mortality related to birth asphyxia?

OBJECTIVE: To find the association of time of referral of asphyxiated newborns with the outcome. DESIGN: Observational study. PLACE AND DURATION OF STUDY: Neonatal Unit of Children's Hospital, Lahore, from August to December 2000. PATIENTS AND METHODS: One hundred fifty newborns with birth asphyxia were studied, who fulfilled four out of six Levene criteria. Exclusion criteria included age more than 48 hours at the time of admission, respiratory depression due to other causes, birth weight less than 1500 grams, gestational age less than 34 weeks, major congenital malformations, dysmorphism, severe hyperbilirubinemia, meningitis and bleeding disorders. Newborns were divided into two groups. Group A (n=78,52%) comprised of those newborns who reached our hospital within 12 hours after birth and group B (n=7, 48%) were those newborns who reached between 12-48 hours. Outcome was described either good outcome (newborns discharged from hospital in good clinical condition having normal vital signs, taking oral feed and not requiring medicine) or poor outcome (newborns expired during stay in neonatal unit). Chi-square test was applied and p-value was calculated. RESULTS: One hundred and seventeen (117) newborns (78%) were males and 33 (22%) were females. Thirty-five (35) mothers (23%) had proper antenatal visits to trained medical professionals. Majority of mothers (n=59, 39%) had their visits to untrained midwives, 56 mothers (37%) to semi-trained persons like a midwife, LHV or nurse. Majority (n =93, 61%) of study population were home delivered. Thirty-six newborns (24%) were delivered at private clinics and maternity homes while only 21 newborns (14%) came from tertiary care centers. Mortality was 24% in group A as compared to 76% in group B (p-value < 0.001). CONCLUSION: Those asphyxiated newborns who reached to a tertiary care hospital earlier had significantly better outcome as compared to those who arrived late. Early recognition of birth asphyxia and referral, therefore, reduces morbidity and mortality.

Age Factors↗
PubMed2006

Myotonia congenita in a brother and sister.

Myotonia congenita is a rare channelopathy and carries a good prognosis. Two cases of young siblings are presented detected with difficulty in gait and motor activities. Both had typical hypertrophied body musculature. EMG was diagnostic.

Child, Preschool↗